Deciphering Hematopoietic Stem Cell Development: Key Signaling Pathways and Mechanisms

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2024 Dec 24

PMID 39717844

Authors

Saori Morino-Koga

Tomomasa Yokomizo

Affiliations

Soon will be listed here.

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 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.

References

He Q, Zhang C, Wang L, Zhang P, Ma D, Lv J . Inflammatory signaling regulates hematopoietic stem and progenitor cell emergence in vertebrates. Blood. 2014; 125(7):1098-106. DOI: 10.1182/blood-2014-09-601542. View

North T, Gu T, Stacy T, Wang Q, Howard L, Binder M . Cbfa2 is required for the formation of intra-aortic hematopoietic clusters. Development. 1999; 126(11):2563-75. DOI: 10.1242/dev.126.11.2563. View

Coulombe P, Cole G, Fentiman A, Parker J, Yung E, Bilenky M . Meis1 establishes the pre-hemogenic endothelial state prior to Runx1 expression. Nat Commun. 2023; 14(1):4537. PMC: 10374625. DOI: 10.1038/s41467-023-40283-0. View

Lengerke C, Schmitt S, Bowman T, Jang I, Maouche-Chretien L, McKinney-Freeman S . BMP and Wnt specify hematopoietic fate by activation of the Cdx-Hox pathway. Cell Stem Cell. 2008; 2(1):72-82. DOI: 10.1016/j.stem.2007.10.022. View

Thambyrajah R, Mazan M, Patel R, Moignard V, Stefanska M, Marinopoulou E . GFI1 proteins orchestrate the emergence of haematopoietic stem cells through recruitment of LSD1. Nat Cell Biol. 2015; 18(1):21-32. DOI: 10.1038/ncb3276. View

Chanda B, Ditadi A, Iscove N, Keller G . Retinoic acid signaling is essential for embryonic hematopoietic stem cell development. Cell. 2013; 155(1):215-27. DOI: 10.1016/j.cell.2013.08.055. View

McGarvey A, Rybtsov S, Souilhol C, Tamagno S, Rice R, Hills D . A molecular roadmap of the AGM region reveals BMPER as a novel regulator of HSC maturation. J Exp Med. 2017; 214(12):3731-3751. PMC: 5716029. DOI: 10.1084/jem.20162012. View

Rho S, Kobayashi I, Oguri-Nakamura E, Ando K, Fujiwara M, Kamimura N . Rap1b Promotes Notch-Signal-Mediated Hematopoietic Stem Cell Development by Enhancing Integrin-Mediated Cell Adhesion. Dev Cell. 2019; 49(5):681-696.e6. DOI: 10.1016/j.devcel.2019.03.023. View

Lee Y, DiMaulo-Milk E, Leslie J, Ding L . Hematopoietic stem cells temporally transition to thrombopoietin dependence in the fetal liver. Sci Adv. 2022; 8(11):eabm7688. PMC: 8926339. DOI: 10.1126/sciadv.abm7688. View

10.

Mariani S, Li Z, Rice S, Krieg C, Fragkogianni S, Robinson M . Pro-inflammatory Aorta-Associated Macrophages Are Involved in Embryonic Development of Hematopoietic Stem Cells. Immunity. 2019; 50(6):1439-1452.e5. PMC: 6591003. DOI: 10.1016/j.immuni.2019.05.003. View

11.

Shivdasani R, Mayer E, Orkin S . Absence of blood formation in mice lacking the T-cell leukaemia oncoprotein tal-1/SCL. Nature. 1995; 373(6513):432-4. DOI: 10.1038/373432a0. View

12.

Frame J, Kubaczka C, Long T, Esain V, Soto R, Hachimi M . Metabolic Regulation of Inflammasome Activity Controls Embryonic Hematopoietic Stem and Progenitor Cell Production. Dev Cell. 2020; 55(2):133-149.e6. PMC: 8008739. DOI: 10.1016/j.devcel.2020.07.015. View

13.

Chen M, Li Y, De Obaldia M, Yang Q, Yzaguirre A, Yamada-Inagawa T . Erythroid/myeloid progenitors and hematopoietic stem cells originate from distinct populations of endothelial cells. Cell Stem Cell. 2011; 9(6):541-52. PMC: 3576591. DOI: 10.1016/j.stem.2011.10.003. View

14.

Fadlullah M, Neo W, Lie-A-Ling M, Thambyrajah R, Patel R, Mevel R . Murine AGM single-cell profiling identifies a continuum of hemogenic endothelium differentiation marked by ACE. Blood. 2021; 139(3):343-356. PMC: 9159109. DOI: 10.1182/blood.2020007885. View

15.

Kobayashi M, Wei H, Yamanashi T, Azevedo Portilho N, Cornelius S, Valiente N . HSC-independent definitive hematopoiesis persists into adult life. Cell Rep. 2023; 42(3):112239. PMC: 10122268. DOI: 10.1016/j.celrep.2023.112239. View

16.

Bresciani E, Carrington B, Yu K, Kim E, Zhen T, Guzman V . Redundant mechanisms driven independently by RUNX1 and GATA2 for hematopoietic development. Blood Adv. 2021; 5(23):4949-4962. PMC: 9153008. DOI: 10.1182/bloodadvances.2020003969. View

17.

Okada H, Watanabe T, Niki M, Takano H, Chiba N, Yanai N . AML1(-/-) embryos do not express certain hematopoiesis-related gene transcripts including those of the PU.1 gene. Oncogene. 1998; 17(18):2287-93. DOI: 10.1038/sj.onc.1202151. View

18.

Lv J, Wang L, Gao Y, Ding Y, Liu F . 5-hydroxytryptamine synthesized in the aorta-gonad-mesonephros regulates hematopoietic stem and progenitor cell survival. J Exp Med. 2016; 214(2):529-545. PMC: 5294845. DOI: 10.1084/jem.20150906. View

19.

Robert-Moreno A, Espinosa L, de la Pompa J, Bigas A . RBPjkappa-dependent Notch function regulates Gata2 and is essential for the formation of intra-embryonic hematopoietic cells. Development. 2005; 132(5):1117-26. DOI: 10.1242/dev.01660. View

20.

Hoogenkamp M, Lichtinger M, Krysinska H, Lancrin C, Clarke D, Williamson A . Early chromatin unfolding by RUNX1: a molecular explanation for differential requirements during specification versus maintenance of the hematopoietic gene expression program. Blood. 2009; 114(2):299-309. PMC: 2714206. DOI: 10.1182/blood-2008-11-191890. View