Stem Cell and Cancer Group, IMIM, Barcelona, Spain.
Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, U.K.
Biochem Soc Trans. 2022 Apr 29;50(2):703-712. doi: 10.1042/BST20210363.
Haematopoietic stem and progenitor cells (HSPCs) sustain haematopoiesis by generating precise numbers of mature blood cells throughout the lifetime of an individual. In vertebrates, HSPCs arise during embryonic development from a specialised endothelial cell population, the haemogenic endothelium (HE). Signalling by the Transforming Growth Factor β (TGFβ) pathway is key to regulate haematopoiesis in the adult bone marrow, but evidence for a role in the formation of HSPCs has only recently started to emerge. In this review, we examine recent work in various model systems that demonstrate a key role for TGFβ signalling in HSPC emergence from the HE. The current evidence underpins two seemingly contradictory views of TGFβ function: as a negative regulator of HSPCs by limiting haematopoietic output from HE, and as a positive regulator, by programming the HE towards the haematopoietic fate. Understanding how to modulate the requirement for TGFβ signalling in HSC emergence may have critical implications for the generation of these cells in vitro for therapeutic use.
造血干细胞和祖细胞 (HSPCs) 通过在个体的整个生命周期中生成精确数量的成熟血细胞来维持造血。在脊椎动物中，HSPCs 是从专门的内皮细胞群——造血内皮细胞 (HE) 中在胚胎发育过程中产生的。转化生长因子 β (TGFβ) 途径的信号对于调节成人骨髓中的造血至关重要，但该途径在 HSPC 形成中的作用的证据直到最近才开始出现。在这篇综述中，我们检查了各种模型系统中的最新工作，这些工作表明 TGFβ 信号在 HSPC 从 HE 中出现中的关键作用。目前的证据支持 TGFβ 功能的两种看似矛盾的观点：作为 HE 中造血输出的负调节剂，限制 HSPC 的产生，以及作为正向调节剂，通过将 HE 编程为造血命运。了解如何调节 TGFβ 信号在 HSC 出现中的需求，对于体外生成这些细胞以用于治疗可能具有重要意义。
