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Human haematopoietic stem cell development: from the embryo to the dish

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TLDR
The extent to which in vitro differentiation of human pluripotent stem cells recapitulates bona fide human developmental haematopoiesis is discussed, and some future directions in the field are outlined.
Abstract
Haematopoietic stem cells (HSCs) emerge during embryogenesis and give rise to the adult haematopoietic system. Understanding how early haematopoietic development occurs is of fundamental importance for basic biology and medical sciences, but our knowledge is still limited compared with what we know of adult HSCs and their microenvironment. This is particularly true for human haematopoiesis, and is reflected in our current inability to recapitulate the development of HSCs from pluripotent stem cells in vitro In this Review, we discuss what is known of human haematopoietic development: the anatomical sites at which it occurs, the different temporal waves of haematopoiesis, the emergence of the first HSCs and the signalling landscape of the haematopoietic niche. We also discuss the extent to which in vitro differentiation of human pluripotent stem cells recapitulates bona fide human developmental haematopoiesis, and outline some future directions in the field.

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Gastruloids as in vitro models of embryonic blood development with spatial and temporal resolution

TL;DR: Gastruloids are three-dimensional embryonic organoids that reproduce key features of early mammalian development in vitro with unique scalability, accessibility, and spatiotemporal similarity to real embryos as discussed by the authors .
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Vast Self-Renewal Potential of Human AGM Region HSCs Dramatically Declines in the Umbilical Cord Blood.

TL;DR: It is quantitatively shown that a single human AGM region HSC can generate 600–1,600 functional daughter HSCs, which sets a new bar for generation of clinically useful H SCs from pluripotent stem cells.
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Biomechanical Regulation of Hematopoietic Stem Cells in the Developing Embryo

TL;DR: In this article, the biomechanics of the endothelial-to-hematopoietic transition (EHT), impact of force on organelles, and signaling triggered by extrinsic forces within the aorta-gonad-mesonephros (AGM), the primary site of HSC emergence.
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Tipping the Scales With Zebrafish to Understand Adaptive Tumor Immunity

TL;DR: In this paper, the authors provide an overview of the development of the zebrafish immune system along with a side-by-side comparison of its human counterpart and introduce components of the adaptive immune system with a focus on their roles in the tumor microenvironment (TME) of teleosts.
References
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Journal ArticleDOI

Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.

TL;DR: Induction of pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture conditions is demonstrated and iPS cells, designated iPS, exhibit the morphology and growth properties of ES cells and express ES cell marker genes.
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Expression of a single transfected cDNA converts fibroblasts to myoblasts.

TL;DR: In this article, the major open reading frame encoded by this cDNA contains a short protein segment similar to a sequence present in the myc protein family, and the expression of one of these cDNAs transfected into C3H10T1/2 fibroblasts, where it is not normally expressed, is sufficient to convert them to stable myoblasts.
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Definitive Hematopoiesis Is Autonomously Initiated by the AGM Region

TL;DR: A novel in vitro organ culture system is presented demonstrating that, at day 10 in gestation, hematopoietic stem cells initiate autonomously and exclusively within the aorta-gonad-mesonephros (AGM) region, suggesting that the AGM region is the source of the definitive adult hematosynthesis system, which subsequently colonizes the liver.
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The SCID-hu mouse: murine model for the analysis of human hematolymphoid differentiation and function.

TL;DR: Experimental data are presented showing that human fetal liver hematopoietic cells, human fetal thymus, and human fetal lymph node support the differentiation of mature human T cells and B cells after engraftment into mice with genetically determined severe combined immunodeficiency.
Journal Article

Multiple defects in innate and adaptive immunologic function in NOD/LtSz-scid mice.

TL;DR: The multiple defects in innate and adaptive immunity unique to the NOD/LtSz-scid/scid mouse provide an excellent in vivo environment for reconstitution with human hematopoietic cells.
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