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Generating human hematopoietic stem cells in vitro –exploring endothelial to hematopoietic transition as a portal for stemness acquisition
Author(s) -
Slukvin Igor I.
Publication year - 2016
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12283
Subject(s) - reprogramming , haematopoiesis , stem cell , biology , microbiology and biotechnology , embryonic stem cell , induced pluripotent stem cell , context (archaeology) , somatic cell , immunology , mesoderm , endothelial stem cell , hemangioblast , in vitro , genetics , cell , paleontology , gene
Advances in cellular reprogramming technologies have created alternative platforms for the production of blood cells, either through inducing pluripotency in somatic cells or by way of direct conversion of nonhematopoietic cells into blood cells. However, de novo generation of hematopoietic stem cells (HSCs) with robust and sustained multilineage engraftment potential remains a significant challenge. Hemogenic endothelium (HE) has been recognized as a unique transitional stage of blood development from mesoderm at which HSCs arise in certain embryonic locations. The major aim of this review is to summarize historical perspectives and recent advances in the investigation of endothelial to hematopoietic transition (EHT) and HSC formation in the context of aiding in vitro approaches to instruct HSC fate from human pluripotent stem cells. In addition, direct conversion of somatic cells to blood and HSCs and progression of this conversion through HE stage are discussed. A thorough understanding of the intrinsic and microenvironmental regulators of EHT that lead to the acquisition of self‐renewal potential by emerging blood cells is essential to advance the technologies for HSC production and expansion.