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Mapping human haematopoietic stem cells from haemogenic endothelium to birth.
Calvanese, Vincenzo; Capellera-Garcia, Sandra; Ma, Feiyang; Fares, Iman; Liebscher, Simone; Ng, Elizabeth S; Ekstrand, Sophia; Aguadé-Gorgorió, Júlia; Vavilina, Anastasia; Lefaudeux, Diane; Nadel, Brian; Li, Jacky Y; Wang, Yanling; Lee, Lydia K; Ardehali, Reza; Iruela-Arispe, M Luisa; Pellegrini, Matteo; Stanley, Ed G; Elefanty, Andrew G; Schenke-Layland, Katja; Mikkola, Hanna K A.
Afiliación
  • Calvanese V; Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA. v.calvanese@ucl.ac.uk.
  • Capellera-Garcia S; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA, USA. v.calvanese@ucl.ac.uk.
  • Ma F; Laboratory for Molecular Cell Biology, University College London, London, UK. v.calvanese@ucl.ac.uk.
  • Fares I; Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA.
  • Liebscher S; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA, USA.
  • Ng ES; Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA.
  • Ekstrand S; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA, USA.
  • Aguadé-Gorgorió J; Chongqing International Institute for Immunology, Chongqing, China.
  • Vavilina A; Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA.
  • Lefaudeux D; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA, USA.
  • Nadel B; Institute of Biomedical Engineering, Department for Medical Technologies and Regenerative Medicine, Eberhard Karls University, Tübingen, Germany.
  • Li JY; Murdoch Children's Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia.
  • Wang Y; Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA.
  • Lee LK; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA, USA.
  • Ardehali R; Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA.
  • Iruela-Arispe ML; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA, USA.
  • Pellegrini M; Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA.
  • Stanley EG; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA, USA.
  • Elefanty AG; Signaling Systems Laboratory, Department of Microbiology Immunology and Molecular Genetics (MIMG), University of California Los Angeles, Los Angeles, CA, USA.
  • Schenke-Layland K; Institute for Quantitative and Computational Biosciences (QCB), University of California Los Angeles, Los Angeles, CA, USA.
  • Mikkola HKA; Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA.
Nature ; 604(7906): 534-540, 2022 04.
Article en En | MEDLINE | ID: mdl-35418685
ABSTRACT
The ontogeny of human haematopoietic stem cells (HSCs) is poorly defined owing to the inability to identify HSCs as they emerge and mature at different haematopoietic sites1. Here we created a single-cell transcriptome map of human haematopoietic tissues from the first trimester to birth and found that the HSC signature RUNX1+HOXA9+MLLT3+MECOM+HLF+SPINK2+ distinguishes HSCs from progenitors throughout gestation. In addition to the aorta-gonad-mesonephros region, nascent HSCs populated the placenta and yolk sac before colonizing the liver at 6 weeks. A comparison of HSCs at different maturation stages revealed the establishment of HSC transcription factor machinery after the emergence of HSCs, whereas their surface phenotype evolved throughout development. The HSC transition to the liver marked a molecular shift evidenced by suppression of surface antigens reflecting nascent HSC identity, and acquisition of the HSC maturity markers CD133 (encoded by PROM1) and HLA-DR. HSC origin was tracked to ALDH1A1+KCNK17+ haemogenic endothelial cells, which arose from an IL33+ALDH1A1+ arterial endothelial subset termed pre-haemogenic endothelial cells. Using spatial transcriptomics and immunofluorescence, we visualized this process in ventrally located intra-aortic haematopoietic clusters. The in vivo map of human HSC ontogeny validated the generation of aorta-gonad-mesonephros-like definitive haematopoietic stem and progenitor cells from human pluripotent stem cells, and serves as a guide to improve their maturation to functional HSCs.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Células Madre Hematopoyéticas / Células Endoteliales Tipo de estudio: Prognostic_studies Límite: Female / Humans / Pregnancy Idioma: En Revista: Nature Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Células Madre Hematopoyéticas / Células Endoteliales Tipo de estudio: Prognostic_studies Límite: Female / Humans / Pregnancy Idioma: En Revista: Nature Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos