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Review
. 2024 Dec 9:12:1510198.
doi: 10.3389/fcell.2024.1510198. eCollection 2024.

Deciphering hematopoietic stem cell development: key signaling pathways and mechanisms

Saori Morino-Koga  1 , Tomomasa Yokomizo  2
Affiliations
Review

Deciphering hematopoietic stem cell development: key signaling pathways and mechanisms

Saori Morino-Koga et al. Front Cell Dev Biol. .

Abstract

Most blood cells derive from hematopoietic stem cells (HSCs), originating from endothelial cells. The induction of HSCs from endothelial cells occurs during mid-gestation, and research has revealed multiple steps in this induction process. Hemogenic endothelial cells emerge within the endothelium, transition to hematopoietic cells (pre-HSCs), and subsequently mature into functional HSCs. Reports indicate transcription factors and external signals are involved in these processes. In this review, we discuss the timing and role of these transcription factors and summarize the external signals that have demonstrated efficacy in an in vitro culture. A precise understanding of the signals at each step is expected to advance the development of methods for inducing HSCs from pluripotent stem cells.

Keywords: aorta-gonad-mesonephros (AGM); endothelial-to-hematopoietic transition (EHT); erythro-myeloid progenitor (EMP); hematopoietic stem cell (HSC); hematopoietic stem cell precursor (pre-HSC); intra-aortic hematopoietic cluster (IAHC).

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

FIGURE 1
FIGURE 1
Transition of cell-surface antigens during HSC development. Hemogenic endothelium expressing endothelial cell markers undergoes EHT and differentiates into pre-HSC-I and pre-HPCs. During this process, some endothelial cell markers are retained while the expression of blood cell markers increases. Pre-HSC-I then differentiates into pre-HSC-II, which express CD45, and ultimately mature into HSCs. VEcad, VE-cadherin.
FIGURE 2
FIGURE 2
scRNA-seq analysis of blood and endothelial cells from E10.5 and E11.5 mouse embryos. The expression patterns of various marker genes: hemogenic endothelium and HPC (Spi1), endothelial cells and pre-HSCs (Mecom), Notch ligands (Dll1, Dll4, Jag1, Jag2), and Notch receptors (Notch1 and Notch4). HPC, hematopoietic progenitor cells; EryP, primitive erythrocytes; EryD, definitive erythrocytes; G/M, granulocytes and monocytes; Mk, megakaryocytes.
FIGURE 3
FIGURE 3
Signaling molecules and transcription factors required for HSC generation in mice. Solid lines indicate the signaling molecules involved in development, while dashed lines indicate those with unclear involvement. RA, retinoic acid; TPO, thrombopoietin; CA, catecholamine.
See this image and copyright information in PMC

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