PMID- 31160568 OWN - NLM STAT- MEDLINE DCOM- 20190624 LR - 20210109 IS - 2041-1723 (Electronic) IS - 2041-1723 (Linking) VI - 10 IP - 1 DP - 2019 Jun 3 TI - A comprehensive single cell transcriptional landscape of human hematopoietic progenitors. PG - 2395 LID - 10.1038/s41467-019-10291-0 [doi] LID - 2395 AB - Hematopoietic Stem/Progenitor cells (HSPCs) are endowed with the role of maintaining a diverse pool of blood cells throughout the human life. Despite recent efforts, the nature of the early cell fate decisions remains contentious. Using single-cell RNA-Seq, we show that existing approaches to stratify bone marrow CD34+ cells reveal a hierarchically-structured transcriptional landscape of hematopoietic differentiation. Still, this landscape misses important early fate decisions. We here provide a broader transcriptional profiling of bone marrow lineage negative hematopoietic progenitors that recovers a key missing branchpoint into basophils and expands our understanding of the underlying structure of early adult human haematopoiesis. We also show that this map has strong similarities in topology and gene expression to that found in mouse. Finally, we identify the sialomucin CD164, as a reliable marker for the earliest branches of HSPCs specification and we showed how its use can foster the design of alternative transplantation cell products. FAU - Pellin, Danilo AU - Pellin D AD - Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA, 02115, USA. FAU - Loperfido, Mariana AU - Loperfido M AUID- ORCID: 0000-0001-9365-5388 AD - Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA, 02115, USA. FAU - Baricordi, Cristina AU - Baricordi C AD - Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA, 02115, USA. FAU - Wolock, Samuel L AU - Wolock SL AUID- ORCID: 0000-0002-2120-4788 AD - Department of Systems Biology, Harvard Medical School, Boston, MA, 02115, USA. FAU - Montepeloso, Annita AU - Montepeloso A AD - Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA, 02115, USA. FAU - Weinberg, Olga K AU - Weinberg OK AD - Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA. FAU - Biffi, Alessandra AU - Biffi A AD - Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA, 02115, USA. FAU - Klein, Allon M AU - Klein AM AUID- ORCID: 0000-0001-8913-7879 AD - Department of Systems Biology, Harvard Medical School, Boston, MA, 02115, USA. Allon_Klein@hms.harvard.edu. FAU - Biasco, Luca AU - Biasco L AD - Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA, 02115, USA. l.biasco@ucl.ac.uk. AD - University College of London (UCL), Great Ormond Street Institute of Child Health Faculty of Population Health Sciences, London, WC1N 1EH, UK. l.biasco@ucl.ac.uk. LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20190603 PL - England TA - Nat Commun JT - Nature communications JID - 101528555 RN - 0 (Antigens, CD34) RN - 0 (CD164 protein, human) RN - 0 (Endolyn) SB - IM MH - Animals MH - Antigens, CD34/metabolism MH - Bone Marrow Cells MH - Cell Lineage MH - Endolyn/metabolism MH - Gene Expression Profiling MH - Hematopoiesis/*genetics MH - Hematopoietic Stem Cells/*metabolism MH - Humans MH - Mice MH - Sequence Analysis, RNA MH - Single-Cell Analysis PMC - PMC6546699 COIS- The authors declare no competing interests. EDAT- 2019/06/05 06:00 MHDA- 2019/06/25 06:00 PMCR- 2019/06/03 CRDT- 2019/06/05 06:00 PHST- 2019/01/11 00:00 [received] PHST- 2019/05/03 00:00 [accepted] PHST- 2019/06/05 06:00 [entrez] PHST- 2019/06/05 06:00 [pubmed] PHST- 2019/06/25 06:00 [medline] PHST- 2019/06/03 00:00 [pmc-release] AID - 10.1038/s41467-019-10291-0 [pii] AID - 10291 [pii] AID - 10.1038/s41467-019-10291-0 [doi] PST - epublish SO - Nat Commun. 2019 Jun 3;10(1):2395. doi: 10.1038/s41467-019-10291-0.