{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T21:07:39Z","timestamp":1793308059498,"version":"4.5.0"},"reference-count":79,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T00:00:00Z","timestamp":1625184000000},"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. Genet."],"abstract":"<jats:p>Intrathymic differentiation of T lymphocytes begins as early as intrauterine stage, yet the T cell lineage decisions of human fetal thymocytes at different gestational ages are not currently understood. Here, we performed integrative single-cell analyses of thymocytes across gestational ages. We identified conserved candidates underlying the selection of T cell receptor (TCR) lineages in different human fetal stages. The trajectory of early thymocyte commitment during fetal growth was also characterized. Comparisons with mouse data revealed conserved and species-specific transcriptional dynamics of thymocyte proliferation, apoptosis and selection. Genome-wide association study (GWAS) data associated with multiple autoimmune disorders were analyzed to characterize susceptibility genes that are highly expressed at specific stages during fetal thymocyte development. In summary, our integrative map describes previously underappreciated aspects of human thymocyte development, and provides a comprehensive reference for understanding T cell lymphopoiesis in a self-tolerant and functional adaptive immune system.<\/jats:p>","DOI":"10.3389\/fgene.2021.679616","type":"journal-article","created":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T15:47:50Z","timestamp":1625240870000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Integrative Single-Cell Transcriptomic Analysis of Human Fetal Thymocyte Development"],"prefix":"10.3389","volume":"12","author":[{"given":"Yuchen","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihong","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyong","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilian","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guolian","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinmei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0927-y","article-title":"Design and computational analysis of single-cell RNA-sequencing experiments.","volume":"17","author":"Bacher","year":"2016","journal-title":"Genome Biol."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02523","article-title":"Single-cell analysis identifies thymic maturation delay in growth-restricted neonatal mice.","volume":"9","author":"Bacon","year":"2018","journal-title":"Front. Immunol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1146\/annurev-immunol-042718-041728","article-title":"The myeloid cell compartment-cell by cell.","volume":"37","author":"Bassler","year":"2019","journal-title":"Annu. Rev. Immunol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2633","DOI":"10.1172\/JCI26471","article-title":"Death versus survival: functional interaction between the apoptotic and stress-inducible heat shock protein pathways.","volume":"115","author":"Beere","year":"2005","journal-title":"J. Clin. Invest."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1242\/dev.152561","article-title":"Mapping human development at single-cell resolution.","volume":"145","author":"Behjati","year":"2018","journal-title":"Development"},{"key":"B6","doi-asserted-by":"publisher","first-page":"D1005","DOI":"10.1093\/nar\/gky1120","article-title":"The NHGRI-EBI GWAS Catalog of published genome-wide association studies, targeted arrays and summary statistics 2019.","volume":"47","author":"Buniello","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1038\/nbt.4096","article-title":"Integrating single-cell transcriptomic data across different conditions, technologies, and species.","volume":"36","author":"Butler","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"103","DOI":"10.4049\/jimmunol.179.1.103","article-title":"Selective role of NFATc3 in positive selection of thymocytes.","volume":"179","author":"Cant\u00e9-Barrett","year":"2007","journal-title":"J. Immunol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.1101\/gad.4.8.1304","article-title":"Developmentally regulated fetal thymic and extrathymic T-cell receptor \u03b3\u03b4 gene expression.","volume":"4","author":"Carding","year":"1990","journal-title":"Genes Dev."},{"key":"B10","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1172\/JCI23087","article-title":"AIRE deficiency in thymus of 2 patients with Omenn syndrome.","volume":"115","author":"Cavadini","year":"2005","journal-title":"J. Clin. Invest."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1182.e","DOI":"10.1016\/j.immuni.2020.10.024","article-title":"An integrated epigenomic and transcriptomic map of mouse and human \u03b1\u03b2 T cell development.","volume":"53","author":"Chopp","year":"2020","journal-title":"Immunity"},{"key":"B12","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1038\/nri2820","article-title":"Determining \u03b3\u03b4 versus \u03b1\u00df T cell development.","volume":"10","author":"Ciofani","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1146\/annurev.immunol.17.1.89","article-title":"Integration of T cell receptor-dependent signaling pathways by adapter proteins.","volume":"17","author":"Clements","year":"1999","journal-title":"Annu. Rev. Immunol."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03282-0","article-title":"Characterizing the replicability of cell types defined by single cell RNA-sequencing data using MetaNeighbor.","volume":"9","author":"Crow","year":"2018","journal-title":"Nat. Commun."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19894-4","article-title":"muscat detects subpopulation-specific state transitions from multi-sample multi-condition single-cell transcriptomics data.","volume":"11","author":"Crowell","year":"2020","journal-title":"Nat. Commun."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1934.e","DOI":"10.1016\/j.celrep.2019.01.079","article-title":"Single-cell transcriptome analysis maps the developmental track of the human heart.","volume":"26","author":"Cui","year":"2019","journal-title":"Cell Rep."},{"key":"B17","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/j.devcel.2009.01.014","article-title":"Transcriptional control of endothelial cell development.","volume":"16","author":"De Val","year":"2009","journal-title":"Dev. Cell"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-020-02048-6","article-title":"Systematic assessment of tissue dissociation and storage biases in single-cell and single-nucleus RNA-seq workflows.","volume":"21","author":"Denisenko","year":"2020","journal-title":"Genome Biol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1718.e","DOI":"10.1016\/j.celrep.2019.09.082","article-title":"DoubletDecon: deconvoluting doublets from single-cell RNA-sequencing data.","volume":"29","author":"DePasquale","year":"2019","journal-title":"Cell Rep."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1715","DOI":"10.1084\/jem.20042524","article-title":"New insights on human T cell development by quantitative T cell receptor gene rearrangement studies and gene expression profiling.","volume":"201","author":"Dik","year":"2005","journal-title":"J. Exp. Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1038\/ni.3437","article-title":"Innate-like functions of natural killer T cell subsets result from highly divergent gene programs.","volume":"17","author":"Engel","year":"2016","journal-title":"Nat. Immunol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1038\/s41422-018-0053-3","article-title":"Spatial transcriptomic survey of human embryonic cerebral cortex by single-cell RNA-seq analysis.","volume":"28","author":"Fan","year":"2018","journal-title":"Cell Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2015","DOI":"10.1242\/dev.087320","article-title":"Dynamics of thymus organogenesis and colonization in early human development.","volume":"140","author":"Farley","year":"2013","journal-title":"Development"},{"key":"B24","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1038\/s41556-018-0105-4","article-title":"Tracing the temporal-spatial transcriptome landscapes of the human fetal digestive tract using single-cell RNA-sequencing.","volume":"20","author":"Gao","year":"2018","journal-title":"Nat. Cell Biol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/j.immuni.2006.01.008","article-title":"Dynamics of thymus-colonizing cells during human development.","volume":"24","author":"Haddad","year":"2006","journal-title":"Immunity"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1874-1","article-title":"Normalization and variance stabilization of single-cell RNA-seq data using regularized negative binomial regression.","volume":"20","author":"Hafemeister","year":"2019","journal-title":"Genome Biol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1038\/nbt.4091","article-title":"Batch effects in single-cell RNA-sequencing data are corrected by matching mutual nearest neighbors.","volume":"36","author":"Haghverdi","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"3101","DOI":"10.1007\/s00018-014-1607-2","article-title":"Tracking migration during human T cell development.","volume":"71","author":"Halkias","year":"2014","journal-title":"Cell. Mol. Life Sci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1038\/s41586-020-2157-4","article-title":"Construction of a human cell landscape at single-cell level.","volume":"581","author":"Han","year":"2020","journal-title":"Nature"},{"key":"B30","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1084\/jem.20142207","article-title":"An anti-silencer- and SATB1-dependent chromatin hub regulates Rag1 and Rag2 gene expression during thymocyte development.","volume":"212","author":"Hao","year":"2015","journal-title":"J. Exp. Med."},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-020-6755-1","article-title":"Transcriptome profiling of human thymic CD4+ and CD8+ T cells compared to primary peripheral T cells.","volume":"21","author":"Helgeland","year":"2020","journal-title":"BMC Genomics"},{"key":"B32","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1016\/j.ceb.2010.08.003","article-title":"Life and death in the thymus\u2013cell death signaling during T cell development.","volume":"22","author":"Hernandez","year":"2010","journal-title":"Curr. Opin. Cell Biol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1038\/s41587-019-0113-3","article-title":"Efficient integration of heterogeneous single-cell transcriptomes using Scanorama.","volume":"37","author":"Hie","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0888-1","article-title":"Classification of low quality cells from single-cell RNA-seq data.","volume":"17","author":"Ilicic","year":"2016","journal-title":"Genome Biol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1101\/gr.110882.110","article-title":"Characterization of the single-cell transcriptional landscape by highly multiplex RNA-seq.","volume":"21","author":"Islam","year":"2011","journal-title":"Genome Res."},{"key":"B36","doi-asserted-by":"publisher","first-page":"2463","DOI":"10.1242\/dev.083147","article-title":"Hematopoiesis.","volume":"140","author":"Jagannathan-Bogdan","year":"2013","journal-title":"Development"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1258.e","DOI":"10.1016\/j.immuni.2018.04.015","article-title":"A single-cell transcriptomic atlas of thymus organogenesis resolves cell types and developmental maturation.","volume":"48","author":"Kernfeld","year":"2018","journal-title":"Immunity"},{"key":"B38","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1038\/nri3389","article-title":"Shades of grey\u2013the blurring view of innate and adaptive immunity.","volume":"13","author":"Lanier","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1016\/j.immuni.2009.07.010","article-title":"Marked induction of the helix-loop-helix protein Id3 promotes the gammadelta T cell fate and renders their functional maturation Notch independent.","volume":"31","author":"Lauritsen","year":"2009","journal-title":"Immunity"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1088.e","DOI":"10.1016\/j.immuni.2020.03.019","article-title":"Integrated scRNA-seq identifies human postnatal thymus seeding progenitors and regulatory dynamics of differentiating immature thymocytes.","volume":"52","author":"Lavaert","year":"2020","journal-title":"Immunity"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1105.e","DOI":"10.1016\/j.immuni.2020.05.010","article-title":"Single-cell RNA-seq mapping of human thymopoiesis reveals lineage specification trajectories and a commitment spectrum in T cell development.","volume":"52","author":"Le","year":"2020","journal-title":"Immunity"},{"key":"B42","doi-asserted-by":"publisher","first-page":"858.e","DOI":"10.1016\/j.stem.2017.03.007","article-title":"Single-cell RNA-Seq analysis maps development of human germline cells and gonadal niche interactions.","volume":"20","author":"Li","year":"2017","journal-title":"Cell Stem Cell"},{"key":"B43","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1182\/blood-2007-09-114181","article-title":"Endogenous galectin-1 enforces class I-restricted TCR functional fate decisions in thymocytes.","volume":"112","author":"Liu","year":"2008","journal-title":"Blood"},{"key":"B44","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1038\/nri1633","article-title":"Transcriptional networks in developing and mature B cells.","volume":"5","author":"Matthias","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1038\/ni.2590","article-title":"The transcriptional landscape of \u03b1\u03b2 T cell differentiation.","volume":"14","author":"Mingueneau","year":"2013","journal-title":"Nat. Immunol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1695","DOI":"10.1126\/science.1196509","article-title":"Fetal and adult hematopoietic stem cells give rise to distinct T cell lineages in humans.","volume":"330","author":"Mold","year":"2010","journal-title":"Science"},{"key":"B47","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1002\/uog.13448","article-title":"International standards for early fetal size and pregnancy dating based on ultrasound measurement of crown-rump length in the first trimester of pregnancy.","volume":"44","author":"Papageorghiou","year":"2014","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1126\/science.aay3224","article-title":"A cell atlas of human thymic development defines T cell repertoire formation.","volume":"367","author":"Park","year":"2020","journal-title":"Science"},{"key":"B49","doi-asserted-by":"publisher","first-page":"784","DOI":"10.4161\/cc.9.4.10673","article-title":"Role of endogenous annexin-A1 in the regulation of thymocyte positive and negative selection.","volume":"9","author":"Paschalidis","year":"2010","journal-title":"Cell Cycle"},{"key":"B50","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1038\/nmeth.4402","article-title":"Reversed graph embedding resolves complex single-cell trajectories.","volume":"14","author":"Qiu","year":"2017","journal-title":"Nat. Methods"},{"key":"B51","doi-asserted-by":"publisher","first-page":"6270","DOI":"10.4049\/jimmunol.167.11.6270","article-title":"Requirement for Ca2+\/calmodulin-dependent kinase type IV\/Gr in setting the thymocyte selection threshold.","volume":"167","author":"Raman","year":"2001","journal-title":"J. Immunol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1817","DOI":"10.1084\/jem.188.10.1817","article-title":"The JNK pathway regulates the In vivo deletion of immature CD4+CD8+ thymocytes.","volume":"188","author":"Rinc\u00f3n","year":"1998","journal-title":"J. Exp. Med."},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2019104159","article-title":"Deciphering the regulatory landscape of fetal and adult \u03b3\u03b4 T-cell development at single-cell resolution.","volume":"39","author":"Sagar, Pokrovskii","year":"2020","journal-title":"EMBO J."},{"key":"B54","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1016\/j.stem.2015.11.004","article-title":"Regulation of ribosome biogenesis and protein synthesis controls germline stem cell differentiation.","volume":"18","author":"Sanchez","year":"2016","journal-title":"Cell Stem Cell"},{"key":"B55","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1146\/annurev-immunol-100219-020937","article-title":"Regulatory T cell development.","volume":"38","author":"Savage","year":"2020","journal-title":"Annu. Rev. Immunol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"5349","DOI":"10.1093\/emboj\/17.18.5349","article-title":"Evidence implicating Gfi-1 and Pim-1 in pre-T-cell differentiation steps associated with \u03b2-selection.","volume":"17","author":"Schmidt","year":"1998","journal-title":"EMBO J."},{"key":"B57","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1038\/nri913","article-title":"Development of \u03b1\u03b2 T cells in the human thymus.","volume":"2","author":"Spits","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1146\/annurev.immunol.21.120601.141107","article-title":"Positive and negative selection of T cells.","volume":"21","author":"Starr","year":"2003","journal-title":"Annu. Rev. Immunol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"1888.e","DOI":"10.1016\/j.cell.2019.05.031","article-title":"Comprehensive Integration of Single-Cell Data.","volume":"177","author":"Stuart","year":"2019","journal-title":"Cell"},{"key":"B60","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1038\/nmeth.4220","article-title":"Power analysis of single-cell RNA-sequencing experiments.","volume":"14","author":"Svensson","year":"2017","journal-title":"Nat. Methods"},{"key":"B61","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1097\/01.gim.0000117333.21213.17","article-title":"Mitochondrial ribosomal proteins: candidate genes for mitochondrial disease.","volume":"6","author":"Sylvester","year":"2004","journal-title":"Genet. Med."},{"key":"B62","doi-asserted-by":"publisher","first-page":"383","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":"B63","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1038\/ni1486","article-title":"Mast cell lineage diversion of T lineage precursors by the essential T cell transcription factor GATA-3.","volume":"8","author":"Taghon","year":"2007","journal-title":"Nat. Immunol."},{"key":"B64","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1146\/annurev-immunol-042617-053411","article-title":"CD4 helper and CD8 cytotoxic T cell differentiation.","volume":"36","author":"Taniuchi","year":"2018","journal-title":"Annu. Rev. Immunol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1182\/blood.v79.3.666.bloodjournal793666","article-title":"Flow cytometric assessment of human T-cell differentiation in thymus and bone marrow.","volume":"79","author":"Terstappen","year":"1992","journal-title":"Blood"},{"key":"B66","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1126\/science.aad0501","article-title":"Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq.","volume":"352","author":"Tirosh","year":"2016","journal-title":"Science"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-41695-z","article-title":"From Louvain to Leiden: guaranteeing well-connected communities.","volume":"9","author":"Traag","year":"2019","journal-title":"Sci. Rep."},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1850-9","article-title":"A benchmark of batch-effect correction methods for single-cell RNA sequencing data.","volume":"21","author":"Tran","year":"2020","journal-title":"Genome Biol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1126\/sciimmunol.aah4232","article-title":"The checkpoint for agonist selection precedes conventional selection in human thymus.","volume":"2","author":"Verstichel","year":"2017","journal-title":"Sci. Immunol."},{"key":"B70","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1038\/mi.2008.84","article-title":"The roles of CCR6 in migration of Th17 cells and regulation of effector T-cell balance in the gut.","volume":"2","author":"Wang","year":"2009","journal-title":"Mucosal Immunol."},{"key":"B71","doi-asserted-by":"publisher","first-page":"3554.e","DOI":"10.1016\/j.celrep.2018.08.056","article-title":"Dissecting the global dynamic molecular profiles of human fetal kidney development by single-cell RNA sequencing.","volume":"24","author":"Wang","year":"2018","journal-title":"Cell Rep."},{"key":"B72","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1038\/nri3690","article-title":"Mast cell secretory granules: armed for battle.","volume":"14","author":"Wernersson","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1084\/jem.20170518","article-title":"IL-7-dependent maintenance of ILC3s is required for normal entry of lymphocytes into lymph nodes.","volume":"215","author":"Yang","year":"2018","journal-title":"J. Exp. Med."},{"key":"B74","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/s0092-8674(02)01250-3","article-title":"Molecular chaperones Hsp90 and Hsp70 deliver preproteins to the mitochondrial import receptor Tom70.","volume":"112","author":"Young","year":"2003","journal-title":"Cell"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1101\/303727","article-title":"SoupX removes ambient RNA contamination from droplet based single cell RNA sequencing data.","author":"Young","year":"2020","journal-title":"bioRxiv"},{"key":"B76","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: an R package for comparing biological themes among gene clusters.","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS"},{"key":"B77","doi-asserted-by":"publisher","first-page":"930.e","DOI":"10.1016\/j.immuni.2019.09.008","article-title":"Single-cell RNA sequencing resolves spatiotemporal development of pre-thymic lymphoid progenitors and thymus organogenesis in human embryos.","volume":"51","author":"Zeng","year":"2019","journal-title":"Immunity"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14049","article-title":"Massively parallel digital transcriptional profiling of single cells.","volume":"8","author":"Zheng","year":"2017","journal-title":"Nat. Commun."},{"key":"B79","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1038\/nature25980","article-title":"A single-cell RNA-seq survey of the developmental landscape of the human prefrontal cortex.","volume":"555","author":"Zhong","year":"2018","journal-title":"Nature"}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2021.679616\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T15:47:58Z","timestamp":1625240878000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2021.679616\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,2]]},"references-count":79,"alternative-id":["10.3389\/fgene.2021.679616"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2021.679616","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,2]]},"article-number":"679616"}}