Understanding the Journey of Human Hematopoietic Stem Cell Development

Figure 3

Established stages of hematopoietic development from hPSCs⁺. The primitive mesodermal precursors are capable of forming mesenchymoangioblast (MB) and hemangioblast (HB) in the presence of FGF2 [62, 122, 125]. Mesodermal commitment to angiohematopoietic development progressively leads to the formation of ^EMHlin⁻KDR^brightAPLNR⁺PDGFRa^low/− hematovascular mesodermal precursors (HVMPs) [62, 89]. The HEP stage was identified based on the expression of the typical endothelial markers VE-cadherin, CD31, and CD34 and the absence of the panhematopoietic marker CD43 [62, 88]. HE cells were distinguished from non-HE cells based on the presence of CD73 expression [62, 132]. Initial hematopoietic progenitors arising from the VE-cadherin+ population show the presence of CD235a, low levels of CD43, and absence of CD41a expression. These cells can form hematopoietic colonies in the presence of FGF2 and retain their endothelial potential. These progenitors were labelled as angiogenic hematopoietic progenitors (AHPs) [62, 132]. Progressive hematopoietic development is identified by the appearance of CD43 expression, and all hematopoietic CFCs are accumulated in this fraction. Distinct subsets of CD43⁺ hematopoietic cells, including CD41a⁺CD235a⁺ erythromegakaryocytic progenitors and lin−CD34⁺CD43⁺CD45^+/− multipotent myelolymphoid progenitors, are also established [63, 88, 89, 105].