Identification of a retinoic acid-dependent haemogenic endothelial progenitor from human pluripotent stem cells.

Autor: Luff SA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai School of Medicine, New York, NY, USA.; Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Medicine, Division of Hematology, Washington University School of Medicine, St Louis, MO, USA., Creamer JP; Department of Medicine, Division of Hematology, Washington University School of Medicine, St Louis, MO, USA., Valsoni S; San Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, Italy., Dege C; Department of Medicine, Division of Hematology, Washington University School of Medicine, St Louis, MO, USA., Scarfò R; San Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, Italy., Dacunto A; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai School of Medicine, New York, NY, USA.; Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Cascione S; San Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, Italy., Randolph LN; San Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, Italy., Cavalca E; San Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, Italy., Merelli I; San Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, Italy.; Institute for Biomedical Technologies, National Research Council, Milan, Italy., Morris SA; Department of Developmental Biology, Washington University in Saint Louis, St Louis, MO, USA.; Department of Genetics, Washington University in Saint Louis, St Louis, MO, USA., Ditadi A; San Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, Italy. ditadi.andrea@hsr.it., Sturgeon CM; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai School of Medicine, New York, NY, USA. christopher.sturgeon@mssm.edu.; Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. christopher.sturgeon@mssm.edu.; Department of Medicine, Division of Hematology, Washington University School of Medicine, St Louis, MO, USA. christopher.sturgeon@mssm.edu.
Jazyk: angličtina
Zdroj: Nature cell biology [Nat Cell Biol] 2022 May; Vol. 24 (5), pp. 616-624. Date of Electronic Publication: 2022 Apr 28.
DOI: 10.1038/s41556-022-00898-9
Abstrakt: The generation of haematopoietic stem cells (HSCs) from human pluripotent stem cells (hPSCs) is a major goal for regenerative medicine. During embryonic development, HSCs derive from haemogenic endothelium (HE) in a NOTCH- and retinoic acid (RA)-dependent manner. Although a WNT-dependent (WNTd) patterning of nascent hPSC mesoderm specifies clonally multipotent intra-embryonic-like HOXA + definitive HE, this HE is functionally unresponsive to RA. Here we show that WNTd mesoderm, before HE specification, is actually composed of two distinct KDR + CD34 neg populations. CXCR4 neg CYP26A1 + mesoderm gives rise to HOXA + multilineage definitive HE in an RA-independent manner, whereas CXCR4 + ALDH1A2 + mesoderm gives rise to HOXA + multilineage definitive HE in a stage-specific, RA-dependent manner. Furthermore, both RA-independent (RAi) and RA-dependent (RAd) HE harbour transcriptional similarity to distinct populations found in the early human embryo, including HSC-competent HE. This revised model of human haematopoietic development provides essential resolution to the regulation and origins of the multiple waves of haematopoiesis. These insights provide the basis for the generation of specific haematopoietic populations, including the de novo specification of HSCs.
(© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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