{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:23:23Z","timestamp":1792650203174,"version":"4.5.0"},"reference-count":73,"publisher":"American Society of Hematology","issue":"23","license":[{"start":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T00:00:00Z","timestamp":1642982400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,6,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Rare hematopoietic stem and progenitor cell (HSPC) pools outside the bone marrow (BM) contribute to blood production in stress and disease but remain ill-defined. Although nonmobilized peripheral blood (PB) is routinely sampled for clinical management, the diagnosis and monitoring potential of PB HSPCs remain untapped, as no healthy PB HSPC baseline has been reported. Here we comprehensively delineate human extramedullary HSPC compartments comparing spleen, PB, and mobilized PB to BM using single-cell RNA-sequencing and\/or functional assays. We uncovered HSPC features shared by extramedullary tissues and others unique to PB. First, in contrast to actively dividing BM HSPCs, we found no evidence of substantial ongoing hematopoiesis in extramedullary tissues at steady state but report increased splenic HSPC proliferative output during stress erythropoiesis. Second, extramedullary hematopoietic stem cells\/multipotent progenitors (HSCs\/MPPs) from spleen, PB, and mobilized PB share a common transcriptional signature and increased abundance of lineage-primed subsets compared with BM. Third, healthy PB HSPCs display a unique bias toward erythroid-megakaryocytic differentiation. At the HSC\/MPP level, this is functionally imparted by a subset of phenotypic CD71+ HSCs\/MPPs, exclusively producing erythrocytes and megakaryocytes, highly abundant in PB but rare in other adult tissues. Finally, the unique erythroid-megakaryocytic\u2013skewing of PB is perturbed with age in essential thrombocythemia and \u03b2-thalassemia. Collectively, we identify extramedullary lineage-primed HSPC reservoirs that are nonproliferative in situ and report involvement of splenic HSPCs during demand-adapted hematopoiesis. Our data also establish aberrant composition and function of circulating HSPCs as potential clinical indicators of BM dysfunction.<\/jats:p>","DOI":"10.1182\/blood.2021013450","type":"journal-article","created":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T21:15:12Z","timestamp":1643058912000},"page":"3387-3401","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":79,"title":["Unique molecular and functional features of extramedullary hematopoietic stem and progenitor cell reservoirs in humans"],"prefix":"10.1182","volume":"139","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5078-2333","authenticated-orcid":false,"given":"Nicole","family":"Mende","sequence":"first","affiliation":[{"name":"1Department\u00a0 of Haematology,"},{"name":"2Wellcome\u2013MRC Cambridge Stem Cell Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8072-4070","authenticated-orcid":false,"given":"Hugo P.","family":"Bastos","sequence":"additional","affiliation":[{"name":"1Department\u00a0 of Haematology,"},{"name":"2Wellcome\u2013MRC Cambridge Stem Cell Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1012-888X","authenticated-orcid":false,"given":"Antonella","family":"Santoro","sequence":"additional","affiliation":[{"name":"1Department\u00a0 of Haematology,"},{"name":"2Wellcome\u2013MRC Cambridge Stem Cell Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1327-2334","authenticated-orcid":false,"given":"Krishnaa T.","family":"Mahbubani","sequence":"additional","affiliation":[{"name":"1Department\u00a0 of Haematology,"},{"name":"3Cambridge NIHR Biomedical Research Centre, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0150-1037","authenticated-orcid":false,"given":"Valerio","family":"Ciaurro","sequence":"additional","affiliation":[{"name":"1Department\u00a0 of Haematology,"},{"name":"2Wellcome\u2013MRC Cambridge Stem Cell Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily F.","family":"Calderbank","sequence":"additional","affiliation":[{"name":"1Department\u00a0 of Haematology,"},{"name":"2Wellcome\u2013MRC Cambridge Stem Cell Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2352-0773","authenticated-orcid":false,"given":"Mariana","family":"Quiroga Londo\u00f1o","sequence":"additional","affiliation":[{"name":"1Department\u00a0 of Haematology,"},{"name":"2Wellcome\u2013MRC Cambridge Stem Cell Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendig","family":"Sham","sequence":"additional","affiliation":[{"name":"1Department\u00a0 of Haematology,"},{"name":"2Wellcome\u2013MRC Cambridge Stem Cell Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7429-7236","authenticated-orcid":false,"given":"Giovanna","family":"Mantica","sequence":"additional","affiliation":[{"name":"1Department\u00a0 of Haematology,"},{"name":"2Wellcome\u2013MRC Cambridge Stem Cell Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Morishima","sequence":"additional","affiliation":[{"name":"4Laboratory of Stem Cell Stress, International Research Centre for Medical Sciences, Centre for Metabolic Regulation of Healthy Aging,"},{"name":"5Laboratory of Hematopoietic Stem Cell Engineering, International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Mitchell","sequence":"additional","affiliation":[{"name":"6Cancer, Ageing and Somatic Mutation Group, Wellcome Sanger Institute, Hinxton, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Rosa","family":"Lidonnici","sequence":"additional","affiliation":[{"name":"7San Raffaele-Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5337-6210","authenticated-orcid":false,"given":"Fabienne","family":"Meier-Abt","sequence":"additional","affiliation":[{"name":"8Department of Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, Zurich, Switzerland;"},{"name":"9Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland;"},{"name":"10Institute of Medical Genetics, University of Zurich, Zurich, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Hayler","sequence":"additional","affiliation":[{"name":"1Department\u00a0 of Haematology,"},{"name":"2Wellcome\u2013MRC Cambridge Stem Cell Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Jardine","sequence":"additional","affiliation":[{"name":"11Biosciences Institute, Newcastle University, Newcastle upon Tyne, United Kingdom;"},{"name":"12Haematology Department, Freeman Hospital, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abbie","family":"Curd","sequence":"additional","affiliation":[{"name":"3Cambridge NIHR Biomedical Research Centre, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom;"},{"name":"13Department of Surgery, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muzlifah","family":"Haniffa","sequence":"additional","affiliation":[{"name":"11Biosciences Institute, Newcastle University, Newcastle upon Tyne, United Kingdom;"},{"name":"14Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom;"},{"name":"15Department of Dermatology and NIHR Newcastle Biomedical Research Centre, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0790-3133","authenticated-orcid":false,"given":"Giuliana","family":"Ferrari","sequence":"additional","affiliation":[{"name":"7San Raffaele-Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, Italy;"},{"name":"16Vita-Salute San Raffaele University, Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5276-5430","authenticated-orcid":false,"given":"Hitoshi","family":"Takizawa","sequence":"additional","affiliation":[{"name":"4Laboratory of Stem Cell Stress, International Research Centre for Medical Sciences, Centre for Metabolic Regulation of Healthy Aging,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0865-7333","authenticated-orcid":false,"given":"Nicola K.","family":"Wilson","sequence":"additional","affiliation":[{"name":"1Department\u00a0 of Haematology,"},{"name":"2Wellcome\u2013MRC Cambridge Stem Cell Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berthold","family":"G\u00f6ttgens","sequence":"additional","affiliation":[{"name":"1Department\u00a0 of Haematology,"},{"name":"2Wellcome\u2013MRC Cambridge Stem Cell Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0633-3696","authenticated-orcid":false,"given":"Kourosh","family":"Saeb-Parsy","sequence":"additional","affiliation":[{"name":"3Cambridge NIHR Biomedical Research Centre, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom;"},{"name":"13Department of Surgery, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8074-6299","authenticated-orcid":false,"given":"Mattia","family":"Frontini","sequence":"additional","affiliation":[{"name":"1Department\u00a0 of Haematology,"},{"name":"17Institute of Biomedical and Clinical Science, College of Medicine and Health, University of Exeter Medical School, Exeter, United Kingdom;"},{"name":"18National Health Service Blood and Transplant, and"},{"name":"19British Heart Foundation Centre of Excellence, Cambridge Biomedical Campus, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9917-9092","authenticated-orcid":false,"given":"Elisa","family":"Laurenti","sequence":"additional","affiliation":[{"name":"1Department\u00a0 of Haematology,"},{"name":"2Wellcome\u2013MRC Cambridge Stem Cell Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"6","key":"2022060915220893900_B1","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1182\/bloodadvances.2016003194","article-title":"Quantification and three-dimensional microanatomical organization of the bone marrow","volume":"1","author":"Nombela-Arrieta","year":"2017","journal-title":"Blood Adv."},{"issue":"1","key":"2022060915220893900_B2","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/sj.bmt.1701039","article-title":"Cadaveric bone marrow and spleen cells for transplantation","volume":"21","author":"S\u00f6derdahl","year":"1998","journal-title":"Bone Marrow Transplant."},{"issue":"7648","key":"2022060915220893900_B3","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/nature21706","article-title":"The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors","volume":"544","author":"Lefran\u00e7ais","year":"2017","journal-title":"Nature."},{"issue":"5","key":"2022060915220893900_B4","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1016\/j.cell.2007.09.047","article-title":"Immunosurveillance by hematopoietic progenitor cells trafficking through blood, lymph, and peripheral tissues","volume":"131","author":"Massberg","year":"2007","journal-title":"Cell."},{"issue":"5548","key":"2022060915220893900_B5","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1126\/science.1064081","article-title":"Physiological migration of hematopoietic stem and progenitor cells","volume":"294","author":"Wright","year":"2001","journal-title":"Science."},{"issue":"12","key":"2022060915220893900_B6","doi-asserted-by":"crossref","first-page":"4507","DOI":"10.1172\/JCI41291","article-title":"Murine erythroid short-term radioprotection requires a BMP4-dependent, self-renewing population of stress erythroid progenitors","volume":"120","author":"Harandi","year":"2010","journal-title":"J Clin Invest."},{"issue":"7","key":"2022060915220893900_B7","doi-asserted-by":"crossref","first-page":"2741","DOI":"10.1182\/blood-2004-02-0703","article-title":"BMP4 and Madh5 regulate the erythroid response to acute anemia","volume":"105","author":"Lenox","year":"2005","journal-title":"Blood."},{"issue":"10","key":"2022060915220893900_B8","doi-asserted-by":"crossref","first-page":"4494","DOI":"10.1182\/blood-2006-04-016154","article-title":"BMP4, SCF, and hypoxia cooperatively regulate the expansion of murine stress erythroid progenitors","volume":"109","author":"Perry","year":"2007","journal-title":"Blood."},{"issue":"12","key":"2022060915220893900_B9","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1038\/modpathol.3800480","article-title":"Morphologic and immunohistochemical evaluation of splenic hematopoietic proliferations in neoplastic and benign disorders","volume":"18","author":"O\u2019Malley","year":"2005","journal-title":"Mod Pathol."},{"issue":"7579","key":"2022060915220893900_B10","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/nature15530","article-title":"A perisinusoidal niche for extramedullary haematopoiesis in the spleen","volume":"527","author":"Inra","year":"2015","journal-title":"Nature."},{"issue":"12","key":"2022060915220893900_B11","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1016\/j.ultrasmedbio.2006.06.017","article-title":"Normal sonographic values of maternal spleen size throughout pregnancy","volume":"32","author":"Maymon","year":"2006","journal-title":"Ultrasound Med Biol."},{"issue":"7484","key":"2022060915220893900_B12","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/nature12932","article-title":"Oestrogen increases haematopoietic stem-cell self-renewal in females and during pregnancy","volume":"505","author":"Nakada","year":"2014","journal-title":"Nature."},{"issue":"9","key":"2022060915220893900_B13","doi-asserted-by":"crossref","first-page":"3392","DOI":"10.1172\/JCI94027","article-title":"27-Hydroxycholesterol induces hematopoietic stem cell mobilization and extramedullary hematopoiesis during pregnancy","volume":"127","author":"Oguro","year":"2017","journal-title":"J Clin Invest."},{"issue":"6","key":"2022060915220893900_B14","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/j.immuni.2012.08.025","article-title":"Dysregulated hematopoietic stem and progenitor cell activity promotes interleukin-23-driven chronic intestinal inflammation","volume":"37","author":"Griseri","year":"2012","journal-title":"Immunity."},{"issue":"14","key":"2022060915220893900_B15","doi-asserted-by":"crossref","first-page":"E376","DOI":"10.1111\/hepr.12319","article-title":"Splenectomy increases the number of circulating hematopoietic stem\/progenitor cells in patients with hepatitis C virus-associated liver cirrhosis","volume":"44","author":"Masuya","year":"2014","journal-title":"Hepatol Res."},{"issue":"4","key":"2022060915220893900_B16","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1097\/PAT.0b013e3283613dbf","article-title":"Up-regulated expression of CXCL12 in human spleens with extramedullary haematopoiesis","volume":"45","author":"Miwa","year":"2013","journal-title":"Pathology."},{"issue":"2","key":"2022060915220893900_B17","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.exphem.2014.10.013","article-title":"C-X-C motif chemokine 12 influences the development of extramedullary hematopoiesis in the spleens of myelofibrosis patients","volume":"43","author":"Wang","year":"2015","journal-title":"Exp Hematol."},{"issue":"3","key":"2022060915220893900_B18","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.exphem.2010.12.008","article-title":"Functional characterization of hematopoietic stem cells in the spleen","volume":"39","author":"Morita","year":"2011","journal-title":"Exp Hematol."},{"issue":"3","key":"2022060915220893900_B19","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.4049\/jimmunol.1701250","article-title":"Identification of a multipotent progenitor population in the spleen that is regulated by NR4A1","volume":"200","author":"Mumau","year":"2018","journal-title":"J Immunol."},{"issue":"11","key":"2022060915220893900_B20","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1016\/j.exphem.2006.06.016","article-title":"Primitive hematopoietic cell populations reside in the spleen: studies in the pig, baboon, and human","volume":"34","author":"Dor","year":"2006","journal-title":"Exp Hematol."},{"key":"2022060915220893900_B21","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.exphem.2021.10.002","article-title":"Hematopoietic stem and progenitor cells outside the bone marrow: where, when, and why","volume":"104","author":"Mende","year":"2021","journal-title":"Exp Hematol."},{"issue":"4","key":"2022060915220893900_B22","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s40778-018-0141-9","article-title":"Peripheral blood stem cell mobilization; a look ahead","volume":"4","author":"Pelus","year":"2018","journal-title":"Curr Stem Cell Rep."},{"issue":"4","key":"2022060915220893900_B23","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/j.stem.2018.08.002","article-title":"Daily onset of light and darkness differentially controls hematopoietic stem cell differentiation and maintenance","volume":"23","author":"Golan","year":"2018","journal-title":"Cell Stem Cell."},{"issue":"4","key":"2022060915220893900_B24","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.stem.2008.09.004","article-title":"Mobilized hematopoietic stem cell yield depends on species-specific circadian timing","volume":"3","author":"Lucas","year":"2008","journal-title":"Cell Stem Cell."},{"issue":"12","key":"2022060915220893900_B25","doi-asserted-by":"crossref","first-page":"2837","DOI":"10.1084\/jem.20090778","article-title":"Niche recycling through division-independent egress of hematopoietic stem cells","volume":"206","author":"Bhattacharya","year":"2009","journal-title":"J Exp Med."},{"issue":"4","key":"2022060915220893900_B26","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1182\/blood-2003-01-0318","article-title":"Mobilization of hematopoietic stem cells during homeostasis and after cytokine exposure","volume":"102","author":"Abkowitz","year":"2003","journal-title":"Blood."},{"issue":"9","key":"2022060915220893900_B27","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1016\/j.exphem.2004.06.010","article-title":"Circulating hematopoietic stem cells do not efficiently home to bone marrow during homeostasis","volume":"32","author":"McKinney-Freeman","year":"2004","journal-title":"Exp Hematol."},{"issue":"12","key":"2022060915220893900_B28","doi-asserted-by":"crossref","first-page":"3249","DOI":"10.1182\/blood.V98.12.3249","article-title":"Diagnostic and clinical relevance of the number of circulating CD34(+) cells in myelofibrosis with myeloid metaplasia","volume":"98","author":"Barosi","year":"2001","journal-title":"Blood."},{"issue":"5","key":"2022060915220893900_B29","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.exphem.2004.02.003","article-title":"Human CD34(+) and CD34(+)CD38(-) hematopoietic progenitors in sickle cell disease differ phenotypically and functionally from normal and suggest distinct subpopulations that generate F cells","volume":"32","author":"Luck","year":"2004","journal-title":"Exp Hematol."},{"issue":"2","key":"2022060915220893900_B30","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/s12288-019-01232-4","article-title":"Higher level of peripheral blood CD34 positive cells presented with unfavorable prognosis in intermediate-low risk acute promyelocytic leukemia","volume":"36","author":"Zhang","year":"2020","journal-title":"Indian J Hematol Blood Transfus."},{"issue":"11","key":"2022060915220893900_B31","doi-asserted-by":"crossref","first-page":"4221","DOI":"10.1073\/pnas.1320753111","article-title":"Circulating hematopoietic stem and progenitor cells are myeloid-biased in cancer patients","volume":"111","author":"Wu","year":"2014","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"4","key":"2022060915220893900_B32","doi-asserted-by":"crossref","first-page":"555","DOI":"10.3324\/haematol.2012.076240","article-title":"Differential effects of the type of iron chelator on the absolute number of hematopoietic peripheral progenitors in patients with \u03b2-thalassemia major","volume":"98","author":"Forni","year":"2013","journal-title":"Haematologica."},{"issue":"4","key":"2022060915220893900_B33","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1111\/trf.13452","article-title":"Hematopoietic peripheral circulating blood stem cells as an independent marker of good transfusion management in patients with \u03b2-thalassemia: results from a preliminary study","volume":"56","author":"Napolitano","year":"2016","journal-title":"Transfusion."},{"issue":"9","key":"2022060915220893900_B34","doi-asserted-by":"crossref","first-page":"e106717","DOI":"10.1371\/journal.pone.0106717","article-title":"Hematopoietic stem cells in neonates: any differences between very preterm and term neonates?","volume":"9","author":"Wisgrill","year":"2014","journal-title":"PLoS One."},{"issue":"1","key":"2022060915220893900_B35","doi-asserted-by":"crossref","first-page":"4100","DOI":"10.1038\/s41467-018-06442-4","article-title":"Myelo-lymphoid lineage restriction occurs in the human haematopoietic stem cell compartment before lymphoid-primed multipotent progenitors","volume":"9","author":"Belluschi","year":"2018","journal-title":"Nat Commun."},{"issue":"1","key":"2022060915220893900_B36","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s13059-016-0939-7","article-title":"Single-cell profiling of human megakaryocyte-erythroid progenitors identifies distinct megakaryocyte and erythroid differentiation pathways","volume":"17","author":"Psaila","year":"2016","journal-title":"Genome Biol."},{"issue":"7","key":"2022060915220893900_B37","doi-asserted-by":"crossref","first-page":"1888","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."},{"issue":"1","key":"2022060915220893900_B38","doi-asserted-by":"crossref","first-page":"5233","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."},{"issue":"7","key":"2022060915220893900_B39","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1038\/ni.2615","article-title":"The transcriptional architecture of early human hematopoiesis identifies multilevel control of lymphoid commitment","volume":"14","author":"Laurenti","year":"2013","journal-title":"Nat Immunol."},{"key":"2022060915220893900_B40","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.exphem.2018.09.004","article-title":"The Human Cell Atlas bone marrow single-cell interactive web portal","volume":"68","author":"Hay","year":"2018","journal-title":"Exp Hematol."},{"issue":"1","key":"2022060915220893900_B41","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1038\/s41467-019-10291-0","article-title":"A comprehensive single cell transcriptional landscape of human hematopoietic progenitors","volume":"10","author":"Pellin","year":"2019","journal-title":"Nat Commun."},{"issue":"7778","key":"2022060915220893900_B42","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/s41586-019-1652-y","article-title":"Decoding human fetal liver haematopoiesis","volume":"574","author":"Popescu","year":"2019","journal-title":"Nature."},{"issue":"4","key":"2022060915220893900_B43","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/ncb3493","article-title":"Human haematopoietic stem cell lineage commitment is a continuous process","volume":"19","author":"Velten","year":"2017","journal-title":"Nat Cell Biol."},{"issue":"3","key":"2022060915220893900_B44","doi-asserted-by":"crossref","first-page":"e8041","DOI":"10.15252\/msb.20178041","article-title":"Molecular transitions in early progenitors during human cord blood hematopoiesis","volume":"14","author":"Zheng","year":"2018","journal-title":"Mol Syst Biol."},{"issue":"6","key":"2022060915220893900_B45","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1093\/bioinformatics\/bts034","article-title":"The sva package for removing batch effects and other unwanted variation in high-throughput experiments","volume":"28","author":"Leek","year":"2012","journal-title":"Bioinformatics."},{"key":"2022060915220893900_B46","doi-asserted-by":"crossref","first-page":"8","DOI":"10.7554\/eLife.48994","article-title":"Self-assembling manifolds in single-cell RNA sequencing data","volume":"8","author":"Tarashansky","year":"2019","journal-title":"eLife."},{"issue":"3","key":"2022060915220893900_B47","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.stem.2015.01.017","article-title":"CDK6 levels regulate quiescence exit in human hematopoietic stem cells","volume":"16","author":"Laurenti","year":"2015","journal-title":"Cell Stem Cell."},{"issue":"6039","key":"2022060915220893900_B48","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1126\/science.1201219","article-title":"Isolation of single human hematopoietic stem cells capable of long-term multilineage engraftment","volume":"333","author":"Notta","year":"2011","journal-title":"Science."},{"issue":"13","key":"2022060915220893900_B49","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1182\/blood-2015-07-660670","article-title":"Human hematopoietic stem cells from mobilized peripheral blood can be purified based on CD49f integrin expression","volume":"126","author":"Huntsman","year":"2015","journal-title":"Blood."},{"issue":"5","key":"2022060915220893900_B50","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/nri3433","article-title":"The ageing haematopoietic stem cell compartment","volume":"13","author":"Geiger","year":"2013","journal-title":"Nat Rev Immunol."},{"issue":"1","key":"2022060915220893900_B51","doi-asserted-by":"crossref","first-page":"11075","DOI":"10.1038\/ncomms11075","article-title":"Single-cell RNA sequencing reveals molecular and functional platelet bias of aged haematopoietic stem cells","volume":"7","author":"Grover","year":"2016","journal-title":"Nat Commun."},{"issue":"8","key":"2022060915220893900_B52","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1016\/j.celrep.2018.10.084","article-title":"The molecular signature of megakaryocyte-erythroid progenitors reveals a role for the cell cycle in fate specification","volume":"25","author":"Lu","year":"2018","journal-title":"Cell Rep."},{"issue":"3","key":"2022060915220893900_B53","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.molcel.2020.04.008","article-title":"Single-cell analyses reveal megakaryocyte-biased hematopoiesis in myelofibrosis and identify mutant clone-specific targets","volume":"78","author":"Psaila","year":"2020","journal-title":"Mol Cell."},{"issue":"3","key":"2022060915220893900_B54","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.stem.2021.01.018","article-title":"Hematopoietic stem cell heterogeneity is linked to the initiation and therapeutic response of myeloproliferative neoplasms","volume":"28","author":"Tong","year":"2021","journal-title":"Cell Stem Cell."},{"issue":"3","key":"2022060915220893900_B55","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.stem.2021.02.001","article-title":"Reconstructing the lineage histories and differentiation trajectories of individual cancer cells in myeloproliferative neoplasms","volume":"28","author":"Van Egeren","year":"2021","journal-title":"Cell Stem Cell."},{"issue":"3","key":"2022060915220893900_B56","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1620\/tjem.197.145","article-title":"Postmortem cytokine levels and the cause of death","volume":"197","author":"Mimasaka","year":"2002","journal-title":"Tohoku J Exp Med."},{"issue":"10","key":"2022060915220893900_B57","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1177\/0963689718785629","article-title":"Brain death-induced inflammatory activity is similar to sepsis-induced cytokine release","volume":"27","author":"Schwarz","year":"2018","journal-title":"Cell Transplant."},{"issue":"1","key":"2022060915220893900_B58","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1136\/hrt.56.1.89","article-title":"Plasma catecholamine changes during cardiopulmonary bypass: a randomised double blind comparison of trimetaphan camsylate and sodium nitroprusside","volume":"56","author":"Corr","year":"1986","journal-title":"Br Heart J."},{"issue":"12","key":"2022060915220893900_B59","doi-asserted-by":"crossref","first-page":"2621","DOI":"10.1097\/TP.0000000000001396","article-title":"Pathophysiological trends during withdrawal of life support: implications for organ donation after circulatory death","volume":"100","author":"Iyer","year":"2016","journal-title":"Transplantation."},{"issue":"41","key":"2022060915220893900_B60","doi-asserted-by":"crossref","first-page":"31661","DOI":"10.1074\/jbc.M110.145037","article-title":"Polarization and migration of hematopoietic stem and progenitor cells rely on the RhoA\/ROCK I pathway and an active reorganization of the microtubule network","volume":"285","author":"Fonseca","year":"2010","journal-title":"J Biol Chem."},{"issue":"10","key":"2022060915220893900_B61","doi-asserted-by":"crossref","first-page":"5614","DOI":"10.1073\/pnas.101546898","article-title":"Rac and Cdc42 GTPases control hematopoietic stem cell shape, adhesion, migration, and mobilization","volume":"98","author":"Yang","year":"2001","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"12","key":"2022060915220893900_B62","doi-asserted-by":"crossref","first-page":"2778","DOI":"10.1084\/jem.20190147","article-title":"A novel disorder involving dyshematopoiesis, inflammation, and HLH due to aberrant CDC42 function","volume":"216","author":"Lam","year":"2019","journal-title":"J Exp Med."},{"issue":"4","key":"2022060915220893900_B63","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1007\/s10875-020-00778-7","article-title":"Infantile myelofibrosis and myeloproliferation with CDC42 dysfunction","volume":"40","author":"Verboon","year":"2020","journal-title":"J Clin Immunol."},{"issue":"5","key":"2022060915220893900_B64","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.stem.2012.04.007","article-title":"Cdc42 activity regulates hematopoietic stem cell aging and rejuvenation","volume":"10","author":"Florian","year":"2012","journal-title":"Cell Stem Cell."},{"issue":"12","key":"2022060915220893900_B65","doi-asserted-by":"crossref","first-page":"3853","DOI":"10.1182\/blood-2007-03-079582","article-title":"Cdc42 critically regulates the balance between myelopoiesis and erythropoiesis","volume":"110","author":"Yang","year":"2007","journal-title":"Blood."},{"issue":"7774","key":"2022060915220893900_B66","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/s41586-019-1531-6","article-title":"Asymmetric lysosome inheritance predicts activation of haematopoietic stem cells","volume":"573","author":"Loeffler","year":"2019","journal-title":"Nature."},{"issue":"31","key":"2022060915220893900_B67","doi-asserted-by":"crossref","first-page":"9638","DOI":"10.1073\/pnas.1512076112","article-title":"Prospective isolation of human erythroid lineage-committed progenitors","volume":"112","author":"Mori","year":"2015","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"3","key":"2022060915220893900_B68","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1046\/j.1365-2141.1999.01226.x","article-title":"Transferrin receptor on peripheral blood lymphocytes in iron deficiency anaemia","volume":"104","author":"Kinik","year":"1999","journal-title":"Br J Haematol."},{"issue":"458","key":"2022060915220893900_B69","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1126\/scitranslmed.aas9563","article-title":"Thrombopoietin receptor-independent stimulation of hematopoietic stem cells by eltrombopag","volume":"10","author":"Kao","year":"2018","journal-title":"Sci Transl Med."},{"issue":"2 Pt 2","key":"2022060915220893900_B70","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/0190-9622(90)70041-F","article-title":"Cutaneous extramedullary hematopoiesis with a preponderance of atypical megakaryocytes in myelofibrosis","volume":"22","author":"Schofield","year":"1990","journal-title":"J Am Acad Dermatol."},{"issue":"24","key":"2022060915220893900_B71","doi-asserted-by":"crossref","first-page":"6310","DOI":"10.1182\/bloodadvances.2020002863","article-title":"Chronic lymphocytic leukemia increases the pool of peripheral blood hematopoietic stem cells and skews differentiation","volume":"4","author":"Santoro","year":"2020","journal-title":"Blood Adv."},{"issue":"5","key":"2022060915220893900_B72","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/nbt.3192","article-title":"Spatial reconstruction of single-cell gene expression data","volume":"33","author":"Satija","year":"2015","journal-title":"Nat Biotechnol."},{"issue":"1-2","key":"2022060915220893900_B73","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.jim.2009.06.008","article-title":"ELDA: extreme limiting dilution analysis for comparing depleted and enriched populations in stem cell and other assays","volume":"347","author":"Hu","year":"2009","journal-title":"J Immunol Methods."}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/139\/23\/3387\/1901231\/bloodbld2021013450.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/139\/23\/3387\/1901231\/bloodbld2021013450.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T15:22:59Z","timestamp":1654788179000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/139\/23\/3387\/483639\/Unique-molecular-and-functional-features-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,9]]},"references-count":73,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2022,6,9]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.2021013450","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,9]]}}}