Single-Cell Approaches to Deconvolute the Development of HSCs

Abstract

Hematopoietic stem cells (HSCs) play a core role in blood development. The ability to efficiently produce HSCs from various pluripotent stem cell sources is the Holy Grail in the hematology field. However, in vitro or in vivo HSC production remains low, which may be attributable to the lack of understanding of hematopoiesis. Here, we review the recent progress in this area and introduce advanced technologies, such as single-cell RNA-seq, spatial transcriptomics, and molecular barcoding, which may help to acquire missing information about HSC generation. We finally discuss unresolved questions, the answers to which may be conducive to HSC production, providing a promising path toward HSC-based immunotherapies.

Hematopoietic Cells from Pluripotent Stem Cells: Hope and Promise for the Treatment of Inherited Blood Disorders

“…PSCs that are derived from somatic cells are called induced PSCs (iPSCs); they are relatively more accessible than ESCs and present advantages such as the possibility to generate autologous cells belonging to the desired tissue. Discovery and development of iPSCs have been extensively reviewed elsewhere [38]. Briefly, in 2006 Yamanaka et al described the possibility to reprogram differentiated murine embryonic fibroblasts into iPSCs in culture following viral-mediated transduction of a cocktail of four main transcriptor factors, namely Oct3/4, Sox2, c-Myc and Klf4 [39].…”

“…We are confident that the continuous refinement and amelioration of current protocols will reach the goal of obtaining HSCs with long-term repopulating capacity. A brief overview of methods to generate HSPCs from PSCs is provided below; detailed protocols have been recently reviewed elsewhere [38,60,69,70]. Although developmental steps to generate primitive and definitive hematopoiesis are the same for mammals, timing and requirement of specific molecules and growth factors vary between mouse and human.…”