Development and regeneration of hematopoietic stem cells

Abstract

Hematopoietic stem cells (HSCs) have the capacity to maintain or reconstitute an organism’s immune system for life. Due to limited supply of these rare cells, the generation of HSCs de novo from readily available cell sources has been a central goal in synthetic immunology. While yet unattained, progress towards that goal has been made along three major strategic avenues. First, developmental mimicking attempts to generate HSCs from pluripotent stem cells (PSCs) by recapitulating the embryonic developmental steps towards HSCs in vitro through temporally controlled exposure to signaling factors and inhibitors. Second, HSC development from PSCs is recapitulated randomly inside a forming teratoma in vivo, and hematopoietic differentiation can be enhanced and directed using hematopoietic stromal cells and cytokines. Third, combinatorial transcription factor-mediated transdifferentiation employs forced expression of transcriptional master regulators with known roles in HSCs to convert somatic cells to HSCs. In this chapter we provide a developmental perspective of HSC emergence and review the promises and challenges of the three major approaches to generate HSCs de novo.