How HSCs Colonize and Expand in the Fetal Niche of the Vertebrate Embryo: An Evolutionary Perspective

Abstract

Rare hematopoietic stem cells (HSCs) can self-renew, establish the entire blood system and represent the basis of regenerative medicine applied to hematological disorders. Clinical use of HSCs is however limited by their inefficient expansion ex vivo, creating a need to further understand HSC expansion in vivo. After embryonic HSCs are born from the hemogenic endothelium, they migrate to the embryonic/fetal niche, where the future adult HSC pool is established by considerable expansion. This takes place at different anatomical sites and is controlled by numerous signals. HSCs then migrate to their adult niche, where they are maintained throughout adulthood. Exactly how HSC expansion is controlled during embryogenesis remains to be characterized and is an important step to improve the therapeutic use of HSCs. We will review the current knowledge of HSC expansion in the different fetal niches across several model organisms and highlight possible clinical applications.

Detection of hematopoietic stem cell transcriptome in human fetal kidneys and kidney organoids derived from human induced pluripotent stem cells (iPSC)

“…Moreover, ZEST cells and kidney cell lines have similar signaling properties. [19,20]. Our results suggest that a "kidney microenvironmental niche" niche could be of interest to generate conditions for HSC culture and expansion.…”

Lfc/Arhgef2 regulates mitotic spindle orientation in hematopoietic stem and progenitor cells and is essential for productive hematopoiesis

“…Indeed, proper establishment of the hematopoietic system during development requires a minimum number of productive HSC divisions in the fetal liver. 56,57 Thus, some but not all Lfc/Arhgef2 -/embryos may generate enough effective HSC divisions to allow for sufficient downstream production of functional progenitors to populate the hematopoietic system. Our results in vivo using adult…”

Biomechanical Regulation of Hematopoietic Stem Cells in the Developing Embryo

“…This is followed by substantial morphological change that allows newly specified HSCs to extravasate from the vascular wall into circulation to travel to the fetal liver [24][25][26][27][28]. The perivascular niche of the fetal liver serves as the next reservoir for HSC development [29]. At E11.5, HSCs begin to colonize the liver where they rapidly expand and differentiate into erythroid, myeloid, and lymphoid progenitors [16,[29][30][31].…”

“…The perivascular niche of the fetal liver serves as the next reservoir for HSC development [29]. At E11.5, HSCs begin to colonize the liver where they rapidly expand and differentiate into erythroid, myeloid, and lymphoid progenitors [16,[29][30][31]. Finally, HSCs migrate to the bone marrow (BM) at E17.5 where they remain throughout the lifetime of the individual [30,32].…”