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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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Journal ArticleDOI

From haematopoietic stem cells to complex differentiation landscapes

TL;DR: These evolving views of haematopoiesis have broad implications for the understanding of the functions of adult stem cells, as well as the development of new therapies for malignant and non-malignant haem atopoietic diseases.
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Decoding human fetal liver haematopoiesis

TL;DR: A shift in the haemopoietic composition of fetal liver during gestation away from being predominantly erythroid, accompanied by a parallel change in differentiation potential of HSC/MPPs is demonstrated, which is validated to produce an integrated map of fetal liver haematopoiesis.
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High-Spatial-Resolution Multi-Omics Sequencing via Deterministic Barcoding in Tissue

TL;DR: D deterministic barcoding in tissue for spatial omics sequencing (DBiT-seq) is presented for co-mapping of mRNAs and proteins in a formaldehyde-fixed tissue slide via next-generation sequencing (NGS) and can be adopted by researchers with no experience in microfluidics.
Journal Article

Biologic properties and enucleation of red blood cells from human embryonic stem cells. Commentary

TL;DR: It is shown that it is feasible to differentiate and mature human embryonic stem cells (hESCs) into functional oxygen-carrying erythrocytes on a large scale (10(10)-10(11) cells/6-well plate hESCs).
References
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Leukosialin (CD43) defines hematopoietic progenitors in human embryonic stem cell differentiation cultures

TL;DR: It is demonstrated that early progenitors committed to hematopoietic development could be identified by surface expression of leukosialin (CD43) and it was demonstrated that the first-appearing CD34(+)CD43(-)CD235a(+) CD41a(+/-)CD45(-) cells represent precommitted erythro-megakaryocytic progenitor.
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Hedgehog Signaling Is Required for Adult Blood Stem Cell Formation in Zebrafish Embryos

TL;DR: It is shown that zebrafish embryos mutant in the Hh pathway or treated with the HH signaling inhibitor cyclopamine display defects in adult hematopoietic stem cell (HSC) formation but not in primitive hematoiesis.
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Distinct Sources of Hematopoietic Progenitors Emerge before HSCs and Provide Functional Blood Cells in the Mammalian Embryo

TL;DR: In this paper, the first murine definitive erythro-myeloid progenitors (EMPs) have an immunophenotype distinct from primitive hematopoietic progenitor, maturing megakaryocytes and macrophages, and rare B cell potential.
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Wnt, Activin, and BMP Signaling Regulate Distinct Stages in the Developmental Pathway from Embryonic Stem Cells to Blood

TL;DR: Findings highlight dynamic changes in signaling requirements during blood cell development and identify a role for Wnt signaling in the establishment of the primitive erythroid lineage.
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B-1 B cell development in the fetus and adult.

TL;DR: Recent studies show that B-1 and B-2 B cells involved in innate and adaptive immune responses, respectively, arise in staggered waves of development from distinct progenitors, and this layered model of B cell development for understanding normal and dysregulated B lymphopoiesis is discussed.
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