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

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.

Single cell transcriptome analysis reveals markers of naïve and lineage-primed hematopoietic progenitors derived from human pluripotent stem cells

“…LMOs proteins, do not present DNA binding domain and rather act through binding of 393 other proteins. This class of protein has not been extensively exploited in programming 394 approaches as much as other transcription factors (Ivanovs et al, 2017). Overexpression 395 of IDs or LMOs could not only provide an alternative approach for programming gene 396 cocktails, but it could also be employed to maintain the progenitor state in culture and 397 prevent their differentiation.…”

Generation and Functional Characterization of Monocytes and Macrophages Derived from Human Induced Pluripotent Stem Cells

“…Previous studies have shown that human induced pluripotent stem cells (hiPSCs) can be induced to form hemogenic endothelium (HE), identified as CD144+CD34+ and CD73‐, which could be further differentiated into CD43+ hematopoietic progenitors (HPCs) and then to erythro‐myeloid progenitors (EMPs); these are reminiscent of EMPs in the yolk sac during embryonic hematopoiesis. The differentiation process is MYB‐independent and associated with HOXA expression (Buchrieser, James, & Moore, 2017; Dou et al., 2016; Ivanovs et al., 2017; Ng et al., 2016; Vanhee et al., 2015), indicating this recapitulates primitive hematopoiesis in vivo. Other studies found that hiPSC‐derived macrophages (iPSDMs) could acquire tissue‐specific characteristics in vitro (Takata et al., 2017) and in vivo (Happle et al., 2018; Takata et al., 2017) by coculture with other tissue‐resident cell types.…”

Robust generation of erythroid and multilineage hematopoietic progenitors from human iPSCs using a scalable monolayer culture system

“…In the developing mammalian embryo, blood is produced in consecutive waves [7][8][9] . The first wave of hematopoietic progenitors, dubbed "primitive", occurs in the yolk sac blood islands 10 .…”