Modeling human yolk sac hematopoiesis with pluripotent stem cells.

Autor:	Atkins MH; McEwen Stem Cell Institute, University Health Network, Toronto, Ontario, Canada.; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada., Scarfò R; San Raffaele Telethon Institute for Gene Therapy, Scientific Institute for Research, Hospitalization and Healthcare, San Raffaele Scientific Institute, Milan, Italy., McGrath KE; Department of Pediatrics, University of Rochester Medical Center, Rochester, NY., Yang D; McEwen Stem Cell Institute, University Health Network, Toronto, Ontario, Canada.; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada., Palis J; Department of Pediatrics, University of Rochester Medical Center, Rochester, NY., Ditadi A; San Raffaele Telethon Institute for Gene Therapy, Scientific Institute for Research, Hospitalization and Healthcare, San Raffaele Scientific Institute, Milan, Italy., Keller GM; McEwen Stem Cell Institute, University Health Network, Toronto, Ontario, Canada.; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Jazyk:	angličtina
Zdroj:	The Journal of experimental medicine [J Exp Med] 2022 Mar 07; Vol. 219 (3). Date of Electronic Publication: 2021 Dec 20.
DOI:	10.1084/jem.20211924
Abstrakt:	In the mouse, the first hematopoietic cells are generated in the yolk sac from the primitive, erythro-myeloid progenitor (EMP) and lymphoid programs that are specified before the emergence of hematopoietic stem cells. While many of the yolk sac-derived populations are transient, specific immune cell progeny seed developing tissues, where they function into adult life. To access the human equivalent of these lineages, we modeled yolk sac hematopoietic development using pluripotent stem cell differentiation. Here, we show that the combination of Activin A, BMP4, and FGF2 induces a population of KDR+CD235a/b+ mesoderm that gives rise to the spectrum of erythroid, myeloid, and T lymphoid lineages characteristic of the mouse yolk sac hematopoietic programs, including the Vδ2+ subset of γ/δ T cells that develops early in the human embryo. Through clonal analyses, we identified a multipotent hematopoietic progenitor with erythroid, myeloid, and T lymphoid potential, suggesting that the yolk sac EMP and lymphoid lineages may develop from a common progenitor. Competing Interests: Disclosures: M.H. Atkins and G.M. Keller reported a patent to "compositions and methods for generating human yolk sac-like hematopoietic cells" pending. G.M. Keller reported personal fees from BlueRock Therapeutics and VistaGen Therapeutics outside the submitted work. No other disclosures were reported. (© 2021 Atkins et al.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu