Modeling human yolk sac hematopoiesis with pluripotent stem cells
Open Access
- 20 December 2021
- journal article
- research article
- Published by Rockefeller University Press in Journal of Experimental Medicine
- Vol. 219 (3)
Abstract
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.Keywords
Funding Information
- Canadian Institutes of Health Research (FDN259937)
- Fondazione Telethon (Project C4)
- National Heart, Lung, and Blood Institute
- National Institutes of Health (R01 HL151777)
- Canadian Institutes of Health Research
This publication has 58 references indexed in Scilit:
- Autonomous murine T-cell progenitor production in the extra-embryonic yolk sac before HSC emergenceBlood, 2012
- CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasisNature, 2011
- A transient definitive erythroid lineage with unique regulation of the β-globin locus in the mammalian embryoBlood, 2011
- Embryonic day 9 yolk sac and intra-embryonic hemogenic endothelium independently generate a B-1 and marginal zone progenitor lacking B-2 potentialProceedings of the National Academy of Sciences, 2011
- The haemangioblast generates haematopoietic cells through a haemogenic endothelium stageNature, 2009
- Development of the hemangioblast defines the onset of hematopoiesis in human ES cell differentiation culturesBlood, 2006
- The megakaryocyte lineage originates from hemangioblast precursors and is an integral component both of primitive and of definitive hematopoiesisBlood, 2006
- Hematopoietic differentiation of human embryonic stem cells progresses through sequential hematoendothelial, primitive, and definitive stages resembling human yolk sac developmentBlood, 2005
- Embryonic Stem Cell Lines Derived from Human BlastocystsScience, 1998
- Origin of Thy-1+ dendritic epidermal cells of adult mice from fetal thymic precursorsNature, 1990