Blood making: learning what to put into the dish

Abstract

The generation of hematopoietic stem cells (HSCs) from pluripotent stem cell (PSC) sources is a long-standing goal that will require a comprehensive understanding of the molecular and cellular factors that determine HSC fate during embryogenesis. A precise interplay between niche components, such as the vascular, mesenchymal, primitive myeloid cells, and the nervous system provides the unique signaling milieu for the emergence of functional HSCs in the aorta-gonad-mesonephros (AGM) region. Over the last several years, the interrogation of these aspects in the embryo model and in the PSC differentiation system has provided valuable knowledge that will continue educating the design of more efficient protocols to enable the differentiation of PSCs into bona fide, functionally transplantable HSCs. Herein, we provide a synopsis of early hematopoietic development, with particular focus on the recent discoveries and remaining questions concerning AGM hematopoiesis. Moreover, we acknowledge the recent advances towards the generation of HSCs in vitro and discuss possible approaches to achieve this goal in light of the current knowledge.

Using Eukaryotic Expression Systems to Generate Human α1,3-Fucosyltransferases That Effectively Create Selectin-Binding Glycans on Stem Cells

“…In these studies, the cells were injected into one femur and engraftment was observed in both femurs, suggesting that stem cells from the initially injected femur migrated to the contralateral femur that wasn't injected. Through the development of improved protocols to derive HSPCs and such technologies as those outlined here, these sources of HSPCs could be that much closer to clinical use 73 .…”

Generation and clinical potential of functional T lymphocytes from gene-edited pluripotent stem cells

“…Transcription factors (TFs) are the core organizers of cell fate [ 97 , 98 ]. Among them, Runx1 is the master regulator of embryonic hematopoietic development [ 99 , 100 ], This factor helps the generation of T cells from PSCs. Transient expression of Runx1 during hematopoietic commitment, enforced the emergence of pre-HSC-like (CD31 + CD41 low CD45 − c-Kit + CD201 high ) inducible hemogenic endothelial cells (iHECs) and HPC-like cells, but not T cells in vitro or in vivo in the further differentiation, indicating that Runx1 alone is not sufficient to initiate the PSC-to-iT program.…”

Crosstalk Between the Hepatic and Hematopoietic Systems During Embryonic Development

“…In vitro generation of HSCs would overcome some of the current clinical difficulties that transplantation faces, however, despite countless efforts to derive HSCs from pluripotent stem cell sources, generation of HSC in vitro has not yet been achieved -reviewed in Freire and Butler (2020). Another possibility to obtain higher numbers of HSCs would be to expand them ex vivo prior to transplantation.…”