Derivation of Hematopoietic Stem and Progenitor Cells from Human Pluripotent Stem Cells
Hematopoietic stem cell (HSC) transplantation is a curative treatment for hematologic malignancies and innate immunodeficiency, but its applications are limited to matched donors, and the availability of umbilical cord blood of immune types. Therefore, derivation of HSCs from patient-specific human induced pluripotent stem cells (hiPSCs) is a holy grail in regenerative medicine. However, derivation of HSCs from iPSCs has proven elusive. Here, the authors developed a method to derive hematopoietic stem and progenitor cells (HSPCs) by combining two established methods. The first method mimics embryonic development by directed differentiation of iPSCs into a cellular state termed hemogenic endothelium (HE) by stepwise exposure to different combinations of morphogens and cytokines. In the second method, transcription factors are induced in HE cells for specification into HSCs. By combining these approaches, the authors identified a set of select transcription factors that programmed HE cells into HSPCs with long-term and multilineage capacity in vivo. In this chapter, I provide an overview of this technology, technical tips, and future applications.
Key wordsPluripotent stem cells Gene regulatory network Hematopoietic stem cells