{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T07:59:39Z","timestamp":1772006379754,"version":"3.50.1"},"reference-count":157,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Radioresistant thymic cells encompass minor subsets of lymphoid precursors of T cells (TLPs), innate lymphoid cells (ILCs), as well as stromal-epithelial and endothelial populations. This review focuses on radioresistant TLPs and their regenerative and functional roles in thymic regeneration following damaging influences, particularly irradiation, as well as their secretory product, referred to as thymocyte growth factor (THGF). Retrospective analysis of experimental data assumes that THGF-producing and THGF-responsive cells correspond to the earliest stage of thymocyte precursors, double-negative (DN) TLPs, of CD117\n                    <jats:sup>-<\/jats:sup>\n                    Thy-1\n                    <jats:sup>+<\/jats:sup>\n                    Sca-1\n                    <jats:sup>+<\/jats:sup>\n                    CD44\n                    <jats:sup>+<\/jats:sup>\n                    CD25\n                    <jats:sup>-<\/jats:sup>\n                    CD4\n                    <jats:sup>-<\/jats:sup>\n                    CD8\n                    <jats:sup>-<\/jats:sup>\n                    phenotype, and may be a target for thymic oncogenesis, when they are in the activated DN1\u2192DN2 stage. Unique features of THGF-driven proliferation of these cells include a colchicine-resistant DNA synthesis and, presumably, the formation of a \u201cdaughter\u201d cell pool within \u201cmother\u201d cell-like structures, as well as the formation of colony-cluster-like structures, which are presumably composed mainly of single activated mother DN1 and surrounding daughter TLPs progressing from DN2 to DN4 stage. This atypical proliferation mode may represent an evolutionarily conserved mechanism of \u201cdefended mitosis\u201d and\/or amitotic or endomitotic pathways division, protecting against radiation-induced injury and thus allowing the cell expansion. THGF, which is induced by \u03b3-irradiation and appears essential for autocrine expansion of radioresistant TLPs, initiates a cascade that enables subsequent responsiveness to IL-7, SCF, IL-2, and additional cytokines. The presented analysis proposes the concept of intrathymic dormant stem cells, which become activated under extreme conditions, and insights into parallels between THGF-responsive cells and other radioresistant thymic populations, suggesting an integrated network of stromal and lymphoid elements that orchestrate thymic regeneration. Together, this review proposes a model in which THGF acts as a critical regulator of dormant intrathymic stem cells, enabling their activation, protected proliferation, and differentiation, and thereby contributing crucially to the lymphoid lineage of thymic regeneration after irradiation, in addition to the concept of the IL-22-dependent pathway of stromal-epithelial regeneration of intrathymic niches microenvironment.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1748485","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T07:03:29Z","timestamp":1772003009000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Radioresistant intrathymic stem cells: retrospective analysis and concept of the role in thymic oncogenesis and post-irradiation regeneration"],"prefix":"10.3389","volume":"17","author":[{"given":"Valentin P.","family":"Shichkin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1567788","article-title":"Early-life homeostatic differentiation of thymus-resident B cells into memory B cells","volume":"16","author":"Casta\u00f1eda","year":"2025","journal-title":"Front Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1595805","article-title":"Thymic B cells in aging and autoimmune disease","volume":"16","author":"Wedemeyer","year":"2025","journal-title":"Front Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1552979","article-title":"Neural regulation of the thymus: past, current, and future perspectives","volume":"16","author":"Carpenter","year":"2025","journal-title":"Front Immunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s12015-020-09955-y","article-title":"Thymus regeneration and future challenges","volume":"16","author":"Shichkin","year":"2020","journal-title":"Stem Cell Rev Rep"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1534444","article-title":"Thymus ad astra, or spaceflight-induced thymic involution","volume":"15","author":"Muramatsu","year":"2025","journal-title":"Front Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1504496","article-title":"Survival and autoimmune risks post-thymectomy","volume":"16","author":"Tsirkin","year":"2025","journal-title":"Front Immunol"},{"key":"B7","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/978-981-16-0301-3_2","article-title":"Stem cells of the thymus","volume-title":"Stem cells: from potential to promise","author":"Shichkin","year":"2021"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.926516","article-title":"Key factors for thymic function and development","volume":"13","author":"Shichkin","year":"2022","journal-title":"Front Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-024-01119-0","article-title":"Endogenous thymic regeneration: restoring T cell production following injury","volume":"25","author":"Granadier","year":"2025","journal-title":"Nat Rev Immunol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.immuni.2025.01.006","article-title":"Recirculating regulatory T cells mediate thymic regeneration through amphiregulin following damage","volume":"58","author":"Lemarquis","year":"2025","journal-title":"Immunity"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0302-0","article-title":"The role of thymic stromal cells in thymocyte development and thymus function","volume":"20","author":"Rossi","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"2428","DOI":"10.1016\/j.devcel.2023.08.017","article-title":"Defining the identity and the niches of epithelial stem cells with highly pleiotropic multilineage potency in the human thymus","volume":"58","author":"Ragazzini","year":"2023","journal-title":"Dev Cell"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1443910","article-title":"The thymus road to a T cell: migration, selection, and atrophy","volume":"15","author":"Ruiz Pe\u00b4rez","year":"2024","journal-title":"Front Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3390\/cells9102226","article-title":"Intrathymic selection and defects in the thymic epithelial cell development","volume":"9","author":"Garc\u00eda-Ceca","year":"2020","journal-title":"Cells."},{"key":"B15","doi-asserted-by":"publisher","first-page":"e13671","DOI":"10.1111\/acel.13671","article-title":"Age-related thymic involution: Mechanisms and functional impact","volume":"21","author":"Liang","year":"2022","journal-title":"Aging Cell"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-024-01915-9","article-title":"Age-related epithelial defects limit thymic function and regeneration","volume":"25","author":"Kousa","year":"2024","journal-title":"Nat Immunol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(02)02265-2","article-title":"One for all and all for one: thymic epithelial stem cells and regeneration","volume":"23","author":"Blackburn","year":"2002","journal-title":"Trends Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cr.7310114","article-title":"Thymic epithelial progenitor cells and thymus regeneration: an update","volume":"17","author":"Zhang","year":"2007","journal-title":"Cell Res"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201545844","article-title":"Adult thymic epithelial cell (TEC) progenitors and TEC stem cells: Model and mechanisms for TEC development and maintenance","volume":"45","author":"Hamazaki","year":"2015","journal-title":"Eur J Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00858","article-title":"Generation and regeneration of thymic epithelial cells","volume":"11","author":"Alawam","year":"2020","journal-title":"Front Immunol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.9309","article-title":"Differentiation of pluripotent stem cells into thymic epithelial cells and generation of thymic organoids: applications for therapeutic strategies against APECED","volume":"13","author":"Provin","year":"2022","journal-title":"Front Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1003490","article-title":"Editorial: Thymus function and aging: A focus on thymic epithelial cells","volume":"13","author":"Shichkin","year":"2022","journal-title":"Front Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1500908","article-title":"Direct and indirect RANK and CD40 signaling regulate the maintenance of thymic epithelial cell frequency and properties in the adult thymus","volume":"15","author":"Hayama","year":"2024","journal-title":"Front Immunol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"dev202853","DOI":"10.1242\/dev.202853","article-title":"Thymic epithelial organoids mediate T-cell development","volume":"151","author":"H\u00fcbscher","year":"2024","journal-title":"Development."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.20944\/preprints202503.1892.v1","article-title":"The cellular and molecular characteristics of postnatal human thymus stromal stem cells","volume":"13","author":"Skelin","year":"2025","journal-title":"Biomedicines."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1093\/jleuko\/qiaf115","article-title":"Mapping murine thymic epithelial cells: functional ultrastructure and implications for thymopoiesis","volume":"117","author":"Vodopyanov","year":"2025","journal-title":"J Leukocyte Biol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-04-1246","article-title":"The chiaroscuro stem cell: a unified stem cell theory","volume":"100","author":"Quesenberry","year":"2002","journal-title":"Blood."},{"key":"B28","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1038\/nrm3980","article-title":"Somatic stem cell heterogeneity: diversity in the blood, skin and intestinal stem cell compartments","volume":"16","author":"Goodell","year":"2015","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-022-01715-w","article-title":"The universal stem cell","volume":"36","author":"Quesenberry","year":"2022","journal-title":"Leukemia."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1242\/dev.128.24.5181","article-title":"Bone marrow-derived cells as progenitors of lung alveolar epithelium","volume":"128","author":"Kotton","year":"2001","journal-title":"Development."},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1080\/14653240310003576","article-title":"Transplanted BM and BM side populationmcells contribute progeny to the lung and liver in irradiated mice","volume":"5","author":"Abe","year":"2003","journal-title":"Cytotherapy."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1172\/JCI18847","article-title":"Bone marrow-derived progenitor cells in pulmonary fibrosis","volume":"113","author":"Hashimoto","year":"2004","journal-title":"J Clin Investig"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200502-309OC","article-title":"Limited restoration of cystic fibrosis lung epithelium in vivo with adult bone marrow-derived cells","author":"Loi","year":"2006","journal-title":"Am J Respir Crit Care Med"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2010.11.062","article-title":"Alveolar epithelial cell therapy with human cord blood-derived hematopoietic progenitor cells","volume":"178","author":"De Paepe","year":"2011","journal-title":"Am J Pathol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-07-235721","article-title":"CC chemokine and 9 deficient hematopoietic progenitors are severely impaired in seeding the adult thymus","volume":"115","author":"Krueger","year":"2010","journal-title":"Blood."},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-08-237784","article-title":"CCR7 and CCR9 together recruit hematopoietic progenitors to the adult thymus","volume":"115","author":"Zlotoff","year":"2010","journal-title":"Blood."},{"key":"B37","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1111\/j.1600-065X.1988.tb00757.x","article-title":"Prethymic and intrathymic mouse T-cell progenitors. Growth Requirements and Analysis of the Expression of Genes Encoding TCR\/T3 Components and Other T-Cell-Specific Molecules","volume":"104","author":"Palacios","year":"1988","journal-title":". Immunol Rev"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.7525","article-title":"Thymic function in the regulation of T cells, and molecular mechanisms underlying the modulation of cytokines and stress signaling","volume":"16","author":"Yan","year":"2017","journal-title":"Mol Med Rep"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2010.08.003","article-title":"Life and death in the thymus-cell death signaling during T cell development","volume":"22","author":"Hernandez","year":"2010","journal-title":"Curr Opin Cell Biol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21165765","article-title":"Thymus inception: molecular network in the early stages of thymus organogenesis","volume":"21","author":"Figueiredo","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/adhm.2021007731","article-title":"Recapitulation of thymic function by tissue engineering strategies","volume":"2100773","author":"Silva","year":"2021","journal-title":"Adv Healthc Mater"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-008-0134-3","article-title":"Molecular mechanisms that control mouse and human TCR\u03b1\u03b2 and TCR\u03b3\u03b4 T cell development","volume":"30","author":"Taghon","year":"2008","journal-title":"Semin Immunopathol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1106652","article-title":"Distinct subpopulations of DN1 thymocytes exhibit preferential \u03b3\u03b4 T lineage potential","author":"Oh","year":"2023","journal-title":"Front Immunol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2004.05.004","article-title":"Heterogeneity among DN1 prothymocytes reveals multiple progenitors with different capacities to generate T cell and non-T cell lineages","volume":"20","author":"Porritt","year":"2004","journal-title":"Immunity."},{"key":"B45","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.cels.2019.09.008","article-title":"Single-cell analysis reveals regulatory gene expression dynamics leading to lineage commitment in early T cell development","volume":"9","author":"Zhou","year":"2019","journal-title":"Cell Syst"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2100408","article-title":"Single-cell RNA sequencing approaches for tracing T cell development","volume":"207","author":"Oh","year":"2021","journal-title":"J Immunol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1016\/j.immuni.2018.09.010","article-title":"Interleukin-17-Producing \u03b3\u03b4 T cells originate from SOX13+ progenitors that are independent of \u03b3\u03b4TCR signaling","volume":"49","author":"Spidale","year":"2018","journal-title":"Immunity."},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.05.071","article-title":"Strong TCRgamma delta signaling prohibits thymic development of IL-17A-Secreting \u03b3\u03b4 T cells","volume":"19","author":"Sumaria","year":"2017","journal-title":"Cell Rep"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.114.1_Part_2.452","article-title":"Thymic regeneration after lethal irradiation: evidence for intrathymic radio-resistant T cell precursors","volume":"114","author":"Kadish","year":"1975","journal-title":"J Immunol"},{"key":"B50","article-title":"Radiation stimulation of the production of thymocyte growth factor and its possible role in thymus recovery","volume":"29","author":"Protsak","year":"1989","journal-title":"Radiobiologiia."},{"key":"B51","article-title":"Properties of intrathymic T-lymphocyte precursors - targets of thymocyte growth factor (THGF)","volume":"1","author":"Shichkin","year":"1990","journal-title":"Biomed Science."},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.144.10.3736","article-title":"Intrathymic radioresistant stem cells follow an IL-2\/IL- 2R pathway during thymic regeneration after sublethal irradiation","volume":"144","author":"Z\u00fa\u00f1iga-Pfl\u00fccker","year":"1990","journal-title":"J Immunol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/0165-2478(92)90069-Z","article-title":"Radioresistant cells of thymus - producers and targets of thymocyte growth factor and their possible role in postradiation restoration of thymus","volume":"33","author":"Shichkin","year":"1992","journal-title":"Immunol Lett"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/0145-305X(94)90017-5","article-title":"Early thymic regeneration after irradiation","volume":"18","author":"Fredrickson","year":"1994","journal-title":"Dev Comp Immunol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.186.Supp.104.21","article-title":"Mechanisms of thymic recovery and T cell reconstitution following sublethal ionizing radiation","volume":"186","author":"K\u00ebpuska","year":"2011","journal-title":"J Immunol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1667\/RR13907.1","article-title":"Radiation-induced thymic damage and its effect on T cell development","volume":"183","author":"Gonzalez","year":"2015","journal-title":"Radiat Res"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2021.02.002","article-title":"Thymic stroma and T-cell progenitors in the context of radiation resistance: Implications for cellular therapy","volume":"28","author":"Fraker","year":"2021","journal-title":"Cell Stem Cell"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01717","article-title":"Detection of quiescent radioresistant epithelial progenitors in the adult thymus","volume":"8","author":"Dumont-Lagac\u00e9","year":"2017","journal-title":"Front Immunol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1080\/09553002.2017.1346825","article-title":"Radiobiological aspects of thymic epithelial cells and T cell development in response to ionizing radiation","volume":"93","author":"Saito","year":"2017","journal-title":"Inter J Rad Biol"},{"key":"B60","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1111\/imr.12651","article-title":"The role of thymic epithelial cells in T cell development and radiation resistance","volume":"282","author":"Akiyama","year":"2018","journal-title":"Immunoll Rev"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.01.013","article-title":"Role of thymic stroma and thymic epithelial cells in radiation resistance and immune recovery","volume":"26","author":"Akkaya","year":"2019","journal-title":"Cell Rep"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1093\/jrr\/rrz062","article-title":"Radiation resistance of thymic epithelial cells: Implications for immune system recovery","volume":"60","author":"Park","year":"2019","journal-title":"J Rad Res"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1667\/RR15081.1","article-title":"The impact of radiation on thymus and thymic stroma: Mechanisms and therapeutic strategies","volume":"192","author":"Zhao","year":"2019","journal-title":"Rad Res"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1186154","article-title":"Acute irradiation causes a long-term disturbance in the heterogeneity and gene expression profile of medullary thymic epithelial cells","volume":"14","author":"Horie","year":"2023","journal-title":"Front Immunol"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.2307\/3571064","article-title":"The effect of total-body X-irradiation on the thymus and the number of its cells","volume":"15","author":"Hofman","year":"1961","journal-title":"Rad Res"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.137.7.2260","article-title":"Proliferation in vitro and interleukin production by 14 day fetal and adult Lyt-2-\/L3T4- mouse thymocytes","volume":"137","author":"Ceredig","year":"1986","journal-title":"J Immunol"},{"key":"B67","article-title":"Surface markers of transformed T-lymphocyte precursors and their reaction to the action of differentiation and growth factors","volume":"5","author":"Shichkin","year":"1988","journal-title":"Immunologiya."},{"key":"B68","article-title":"T-lymphocyte precursors - target cells of the thymocyte growth factor","volume":"4","author":"Protsak","year":"1989","journal-title":"Bull Exp Biol Med"},{"key":"B69","first-page":"65","article-title":"\u2018Radioresistant\u2019 CD4-CD8- intrathymic T cell precursors differentiate into mature CD4+CD8- and CD4-CD8+T cells","volume":"15","author":"Ayukawa","year":"1990","journal-title":"Thymus."},{"key":"B70","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.thyr.2013.12.002","article-title":"The thymus as a target for radiation damage and its role in immune recovery","volume":"35","author":"Levy","year":"2014","journal-title":"Thymus Res"},{"key":"B71","article-title":"The humoral mediation of the regulatory effect of T-lymphocyte precursors on haemopoiesis","volume":"4","author":"Sharova","year":"1987","journal-title":"Immunologiya."},{"key":"B72","article-title":"Production, biological properties and phisico-chemical characteristics of thymocyte growth factor secreted by cell lines of intrathymic T-lymphocyte precursors","volume":"6","author":"Shichkin","year":"1988","journal-title":"Immunologiya."},{"key":"B73","article-title":"Bone marrow and intrathymic precursors of T-cells produce a factor which enhances colony formation in the spleen","volume":"1","author":"Yarilin","year":"1990","journal-title":"Biomed Science."},{"key":"B74","article-title":"Lines of transformed thymus cells of mice. I. Line obtaining","volume":"29","author":"Shichkin","year":"1987","journal-title":"Tsytologiya."},{"key":"B75","article-title":"Purification and characterization of a thymocyte growth factor. 1. Purification","volume":"2","author":"Talaev","year":"1991","journal-title":"Biomed Science."},{"key":"B76","article-title":"Purification and characterization of a thymocyte growth factor. 2. Biological activity of the thymocyte growth factor","volume":"2","author":"Talaev","year":"1991","journal-title":"Biomed Science."},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1084\/jem.136.2.369","article-title":"Brain-associated stem cell antigen: an antigen shared by brain and hemopoietic stem cells","volume":"136","author":"Golub","year":"1972","journal-title":"J Exp Med"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830120502","article-title":"Thy-1 determinants are present on many murine hematopoietic cells other than T cells","volume":"12","author":"Basch","year":"1982","journal-title":"Eur J Immunol"},{"key":"B79","article-title":"The interaction of bone marrow cells carrying the \u2018stem cell antigen\u2019 and those lacking it in the formation of colonies in the spleen","volume":"6","author":"Yarilin","year":"1985","journal-title":"Immunologiya."},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.133.6.2940","article-title":"Thy-1 antigen expression by murine high-proliferative capacity hematopoietic progenitor cells. I. Relation between sensitivity to depletion by Thy-1 antibody and stem cell generation potential","volume":"133","author":"Boswell","year":"1984","journal-title":"J Immunol"},{"key":"B81","article-title":"Characteristics of the intrathymic precursors of T-lymphocytes","volume":"6","author":"Miroshnichenko","year":"1987","journal-title":"Immunologiya."},{"key":"B82","first-page":"29","article-title":"Activated precursors of T-lymphocytes carrying the Thy-1 antigen","volume":"2","author":"Miroshnichenko","year":"1987","journal-title":"Immunologiya."},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1084\/jem.184.2.759","article-title":"Identification of CD8 as a peanut agglutinin (PNA) receptor molecule on immature thymocytes","volume":"184","author":"Wu","year":"1996","journal-title":"J Exp Med"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/7.3.349","article-title":"Developmentally regulated expression of peanut agglutinin (PNA)-specific glycans on murine thymocytes","volume":"7","author":"Wu","year":"1997","journal-title":"Glycobiology."},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1038\/314101a0","article-title":"Expression and function of interleukin 2 receptors on immature thymocytes","volume":"314","author":"Raulet","year":"1985","journal-title":"Nature."},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.134.6.3632","article-title":"Identification of early stages of T lymphocyte development in the thymus cortex and medulla","volume":"134","author":"Scollay","year":"1985","journal-title":"J Immunol"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.141.11.3697","article-title":"The stem cell antigens Sca-1 and Sca-2 subdivide thymic and peripheral T lymphocytes into unique subsets","volume":"141","author":"Spangrude","year":"1988","journal-title":"J Immunol"},{"key":"B88","doi-asserted-by":"publisher","first-page":"11396","DOI":"10.1038\/s41598-020-67827-4","article-title":"TGF-\u03b2 regulates Sca-1 expression and plasticity of pre-neoplastic mammary epithelial stem cells","volume":"10","author":"Rem\u0161\u00edk","year":"2020","journal-title":"Sci Rep"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.20674","article-title":"Mouse hematopoietic stem cell identification and analysis","author":"Challen","year":"2009","journal-title":"Cytometry."},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1593\/neo.08902","article-title":"SCA-1 identifies the tumor-initiating cells in mammary tumors of BALB-neuT transgenic mice","volume":"10","author":"Grange","year":"2008","journal-title":"Neoplasia."},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2006-0644","article-title":"Concise review: stem cell antigen-1: expression, function, and enigma","volume":"25","author":"Holmes","year":"2007","journal-title":"Stem Cells"},{"key":"B92","doi-asserted-by":"publisher","first-page":"e0129561","DOI":"10.1371\/journal.pone.0129561","article-title":"Negative regulation of TGFbeta signaling by stem cell antigen-1 protects against ischemic acute kidney injury","volume":"10","author":"Camarata","year":"2015","journal-title":"PloS One"},{"key":"B93","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1038\/s41421-021-00303-z","article-title":"Sca1 marks a reserve endothelial progenitor population that preferentially expand after injury","volume":"7","author":"Tang","year":"2021","journal-title":"Cell Discov"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2005.04.001","article-title":"Roles of Sca-1 in hematopoietic stem\/progenitor cell function","volume":"33","author":"Bradfute","year":"2005","journal-title":"Exp Hematol"},{"key":"B95","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/S0165-2478(96)02682-X","article-title":"Stem cell antigen 2 expression in adult and developing mice","volume":"55","author":"Antica","year":"1997","journal-title":"Immunol Lett"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V84.1.111.111","article-title":"Thymic stem cells in mouse bone marrow","volume":"84","author":"Antica","year":"1994","journal-title":"Blood."},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.12.5296","article-title":"Mouse stem cell antigen Sca-2 is a member of the Ly-6 family of cell surface proteins","volume":"91","author":"Classon","year":"1994","journal-title":"Proceed Nat Acad Sci USA"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1084\/jem.174.6.1617","article-title":"Developmental potential of the earliest precursor cells from the adult mouse thymus","volume":"174","author":"Wu","year":"1991","journal-title":"J Exp Med"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.151.12.6913","article-title":"Isolation of a cDNA encoding thymic shared antigen-1. A new member of the Ly6 family with a possible role in T cell development","volume":"151","author":"MacNeil","year":"1993","journal-title":". J Immunol"},{"key":"B100","doi-asserted-by":"publisher","first-page":"6170","DOI":"10.1038\/s41467-025-61125-1","article-title":"Kitlo hematopoietic stem cells exhibit distinct lymphoid-primed chromatin landscapes that enhance thymic reconstitution","volume":"16","author":"Elias","year":"2025","journal-title":"Nat Commun"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.3389\/frhem.2024.1463410","article-title":"Early T-cell precursor acute lymphoblastic leukemia: diagnostic pitfalls, genomic alteration, novel therapeutics, and minimal residual disease monitoring","volume":"3","author":"George","year":"2024","journal-title":"Front Hematol"},{"key":"B102","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1182\/blood.2023023155","article-title":"How I treat ETP-ALL in children","volume":"145","author":"Summers","year":"2025","journal-title":"Blood"},{"key":"B103","article-title":"Lines of transformed mouse thymus cells. II. Cell morphology, karyology, ultrastructure and growth in vitro and in vivo","volume":"29","author":"Shichkin","year":"1987","journal-title":"Tsitologiya."},{"key":"B104","volume-title":"Analysis of the properties of intrathymic precursors of T-lymphocytes and their products using sta ble cell lines [doctoral dissertation]","author":"Shichkin","year":"1990"},{"key":"B105","doi-asserted-by":"publisher","first-page":"26442648","DOI":"10.4049\/jimmunol.132.5.2644","article-title":"Cell surface antigen phenotypes of MCF-induced thymic lymphomas in AKR mice","volume":"132","author":"Yetter","year":"1984","journal-title":"J Immunol"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/75.3.491","article-title":"Development of virus-accelerated thymic lymphoma in AKR mice","volume":"75","author":"Kato","year":"1985","journal-title":"JNCI: J Nat Cancer Inst"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/8.1.163","article-title":"Induction of thymomas by N -methyl- N -nitrosourea in AKR mice: interaction between the chemical carcinogen and endogenous murine leukaemia viruses","volume":"8","author":"Warren","year":"1987","journal-title":"Carcinogenesis."},{"key":"B108","article-title":"Progression to development of lymphoma in the thymus of AKR mice treated neonatally with SL 3\u20133 virus","volume":"17","author":"Hays","year":"1989","journal-title":"Exp Hematol"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16122224","article-title":"Mechanisms underlying the development of murine T-cell lymphoblastic lymphoma\/leukemia induced by total-body irradiation","volume":"16","author":"Sado","year":"2024","journal-title":"Cancers (Basel)."},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.2174\/0929867043455972","article-title":"Cytokines in the thymus: production and biological effects","volume":"11","author":"Yarilin","year":"2004","journal-title":"Curr Med Chem"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1016\/0952-7915(94)90094-9","article-title":"Early stages in human and mouse T-cell development","volume":"6","author":"Spits","year":"1994","journal-title":"Curr Opin Immunol"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.02.001","article-title":"Interleukin-2 signaling in the regulation of T cell biology in autoimmunity and cancer","volume":"57","author":"Shouse","year":"2024","journal-title":"Immunity."},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.12.006","article-title":"Signaling through the inhibitory fc receptor fcgRIIB induces CD8+ T cell apoptosis to limit T cell immunity","volume":"52","author":"Morris","year":"2020","journal-title":"Immunity."},{"key":"B114","doi-asserted-by":"publisher","first-page":"5981","DOI":"10.1038\/s41467-024-50266-4","article-title":"Antibody Fc-receptor Fc\u03f5R1\u03b3 stabilizes cell surface receptors in group 3 innate lymphoid cells and promotes anti-infection immunity","volume":"15","author":"Huang","year":"2024","journal-title":"Nat Commun"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V74.4.1368.1368","article-title":"Murine thymocytes proliferate in direct response to interleukin-7","volume":"74","author":"Conlon","year":"1989","journal-title":"Blood."},{"key":"B116","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1111\/j.1749-6632.2009.05300.x","article-title":"Effects of sleep and circadian rhythm on the human immune system","volume":"1193","author":"Lange","year":"2010","journal-title":"Ann N Y Acad Sci"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1177\/0748730415577723","article-title":"Circadian clocks in the immune system","volume":"30","author":"Labrecque","year":"2015","journal-title":"J Biol Rhythms."},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-018-0008-4","article-title":"Clocking in to immunity","volume":"18","author":"Scheiermann","year":"2018","journal-title":"Nat Rev Immunol"},{"key":"B119","article-title":"Thy-1 antigen expression by murine hematopoietic precursor cells","volume":"13","author":"Berman","year":"1985","journal-title":"Exp Hematol"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1080\/09553000600930699","article-title":"Effect of gamma radiation on cytokine expression and cytokine-receptor mediated STAT activation","author":"Han","year":"2006","journal-title":"Int J Radiat Biol"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1667\/RR3031.1","article-title":"Cytokines in radiobiological responses: a review","volume":"178","author":"Schaue","year":"2012","journal-title":"Radiat Res"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2011.12.023","article-title":"Response patterns of cytokines\/chemokines in two murine strains after irradiation","volume":"58","author":"Zhang","year":"2012","journal-title":"Cytokine."},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1093\/jrr\/rry067","article-title":"Cytokines and radiation-induced pulmonary injuries","volume":"59","author":"Lierova","year":"2018","journal-title":"J Rad Res"},{"key":"B124","first-page":"17","article-title":"Proliferative response to cytokine and phenotype profile of long-lived thymocytes","volume-title":"Proceedings of the 3rd joint meeting of the ICS\/ISICR; 2000 nov 5-9","author":"Shichkin","year":"2000"},{"key":"B125","article-title":"Interleukin-7 a major T-lymphocyte cytokine","volume":"4","author":"Costello","year":"1993","journal-title":"Eur Cytokine Netw"},{"key":"B126","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1016\/j.jaci.2010.11.050","article-title":"Interleukins, from 1 to 37, and interferon-\u03b3: receptors, functions, and roles in diseases","volume":"127","author":"Akdis","year":"2011","journal-title":"J Allergy Clin Immunol"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2022.156049","article-title":"IL-7: comprehensive review","volume":"160","author":"Winer","year":"2022","journal-title":"Cytokine."},{"key":"B128","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.bbmt.2010.07.027","article-title":"Combined effects of interleukin-7 and stem cell factor administration on lymphopoiesis after murine bone marrow transplantation","volume":"17","author":"Chung","year":"2011","journal-title":"Biol Blood Marrow Transplant."},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1038\/333571a0:571","article-title":"Stimulation of B-cell progenitors by cloned murine interleukin-7","volume":"333","author":"Namen","year":"1988","journal-title":"Nature."},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0809559106","article-title":"Characterization of the thymic IL-7 niche in vivo","volume":"106","author":"Alves","year":"2009","journal-title":"Proc Natl Acad Sci U S A."},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3171","article-title":"Thymic regulatory T cell niche size is dictated by limiting IL-2 from antigen-bearing dendritic cells and feedback competition","volume":"16","author":"Weist","year":"2015","journal-title":"Nat Immunol"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.1006\/cyto.1999.0614","article-title":"Autocrine and paracrine regulation by cytokines and growth factors in melanoma","volume":"12","author":"L\u00e1z\u00e1r-Moln\u00e1r","year":"2000","journal-title":"Cytokine."},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.883560","article-title":"Role of cytokines in thymic regulatory T cell generation: overview and updates","volume":"13","author":"Tang","year":"2022","journal-title":"Front Immunol"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110632","article-title":"Autocrine and paracrine IL-2 signals collaborate to regulate distinct phases of CD8 T cell memory","volume":"39","author":"Toumi","year":"2022","journal-title":"Cell Rep"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-025-02864-w","article-title":"Mesenchymal thymic niche cells enable regeneration of the adult thymus and T cell immunity","author":"Gustafsson","year":"2025","journal-title":"Nat Biotechnol"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.1126\/science.1218004","article-title":"Interleukin-22 drives endogenous thymic regeneration in mice","volume":"336","author":"Dudakov","year":"2012","journal-title":"Science."},{"key":"B137","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032414-112123","article-title":"Interleukin-22: immunobiology and pathology","volume":"21","author":"Dudakov","year":"2015","journal-title":"Annu Rev Immunol"},{"key":"B138","volume-title":"Adding insult to injury: improving regenerative capacity of the aged thymus following clinically induced damage","author":"Dudakov","year":"2019"},{"key":"B139","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2019.06.002","article-title":"IL-22 Accelerates Thymus Regeneration via Stat3\/Mcl-1 and Decreases Chronic Graft-versus-Host Disease in Mice after Allotransplants","volume":"25","author":"Pan","year":"2019","journal-title":"Biol Blood Marrow Transplant."},{"key":"B140","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1016\/j.exphem.2009.12.006","article-title":"Auto-reconstitution of the T-cell compartment by radioresistant hematopoietic cells following lethal irradiation and bone marrow transplantation","volume":"38","author":"Bosco","year":"2010","journal-title":"Exp Hematol"},{"key":"B141","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01312","article-title":"DN2 thymocytes activate a specific robust DNA damage response to ionizing radiation-induced DNA double-strand breaks","volume":"9","author":"Calvo-Asensio","year":"2018","journal-title":"Front Immunol"},{"key":"B142","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.137.10.3195","article-title":"Role of interleukin 1 in early T cell development: Lyt-2-L3T4- thymocytes bind and respond in vitro to recombinant IL 1","volume":"137","author":"Howe","year":"1986","journal-title":"J Immunol"},{"key":"B143","article-title":"The biological properties of interleukin-1","volume":"5","author":"Dinarello","year":"1994","journal-title":"Eur Cytokine Netw"},{"key":"B144","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1016\/j.coi.2011.08.003","article-title":"IL-2 family cytokines: new insights into the complex roles of IL-2 as a broad regulator of T helper cell differentiation","author":"Liao","year":"2011","journal-title":"Curr Opin Immunol"},{"key":"B145","first-page":"436","article-title":"Spontaneous development of thymic cell populations in long-term cultures of mouse and human thymuses","volume-title":"Proceedings of the 4th euripean congress of immunology","author":"Shichkin","year":"2015"},{"key":"B146","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2021.105138","article-title":"Investigation of molecular mechanisms underlying the antiproliferative effects of colchicine against PC3 prostate cancer cells","volume":"73","author":"Ergul","year":"2021","journal-title":"Toxicol In Vitro."},{"key":"B147","doi-asserted-by":"publisher","DOI":"10.1038\/nri2989","article-title":"Signal integration and crosstalk during thymocyte migration and emigration","volume":"11","author":"Love","year":"2011","journal-title":"Nat Rev Immunol"},{"key":"B148","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-015-1864-8","article-title":"Transcription factors and target genes of pre-TCR signaling","volume":"72","author":"L\u00f3pez-Rodr\u00edguez","year":"2015","journal-title":"Cell Mol Life Sci"},{"key":"B149","doi-asserted-by":"publisher","first-page":"vlaf035","DOI":"10.1093\/immhor\/vlaf035","article-title":"Maturation of thymocytes with a monoclonal TCR under control of Trac promoter elements in the absence of \u03b2-selection","volume":"9","author":"Tsai","year":"2025","journal-title":"Immunohorizons."},{"key":"B150","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(86)90030-7","article-title":"Thymic nurse cells: possible sites of T-cell selection","volume":"7","author":"Kyewski","year":"1986","journal-title":"Immunol Today"},{"key":"B151","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1202573","article-title":"IL-7 produced by thymic epithelial cells plays a major role in the development of thymocytes and TCR\u03b3\u03b4+ intraepithelial lymphocytes","volume":"190","author":"Shitara","year":"2013","journal-title":"J Immunol"},{"key":"B152","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/0008-8749(89)90226-8","article-title":"Nature of the thymocytes associated with dendritic cells and macrophages in thymic rosettes","volume":"119","author":"Shortman","year":"1989","journal-title":"Cell Immunol"},{"key":"B153","doi-asserted-by":"publisher","DOI":"10.1155\/1991\/49025","article-title":"Different subpopulations of developing thymocytes are associated with adherent (Macrophage) or nonadherent (Dendritic) thymic rosettes","volume":"1","author":"Shortman","year":"1991","journal-title":"Dev Immunol"},{"key":"B154","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-06-359679","article-title":"Development of thymic NK cells from double negative 1 thymocyte precursors","volume":"118","author":"Vargas","year":"2011","journal-title":"Blood."},{"key":"B155","doi-asserted-by":"publisher","DOI":"10.1016\/s0145-305x(98)00012-3","article-title":"A linkage between dendritic cell and T-cell development in the mouse thymus: the capacity of sequential T-cell precursors to form dendritic cells in culture","volume":"22","author":"Lucas","year":"1998","journal-title":"Dev Comp Immunol"},{"key":"B156","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830240345","article-title":"In vitro development of B cells and macrophages from early mouse fetal thymocytes","volume":"24","author":"P\u00e9ault","year":"1994","journal-title":"Eur J Immunol"},{"key":"B157","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aal2736","article-title":"Production of BMP4 by endothelial cells is crucial for endogenous thymic regeneration","volume":"3","author":"Wertheimer","year":"2018","journal-title":"Sci Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1748485\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T07:03:33Z","timestamp":1772003013000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1748485\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,25]]},"references-count":157,"alternative-id":["10.3389\/fimmu.2026.1748485"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1748485","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,25]]},"article-number":"1748485"}}