Department of Pathology and Immunology, Developmental, Regenerative, and Stem Cell Biology Program, Washington University School of Medicine, St. Louis, Missouri, USA.
Graduate School of Biotechnology, Kyung Hee University, Yong In, South Korea.
Curr Opin Hematol. 2018 Jul;25(4):253-258. doi: 10.1097/MOH.0000000000000430.
Recent studies have established that haematopoietic stem cells (HSCs) remain quiescent in homeostatic conditions, and minimally contribute to haematopoietic homeostasis. However, they undergo extensive cell cycle and expansion upon bone marrow transplantation or haematopoietic injury to reestablish the haematopoietic system. Molecular basis for the HSC activation and expansion is not completely understood. Here, we review the recent study elucidating the role of the developmentally critical Ets transcription factor Etv2 in reestablishing haematopoietic system upon injury through promoting HSC regeneration.
We recently demonstrated that the ETS transcription factor Etv2, a critical factor for haematopoietic and vascular development, is also required for haematopoietic regeneration. Etv2, which is silent in homeostatic HSCs, was transiently activated in regenerating HSPCs and was required for the HSC expansion and regeneration following bone marrow transplantation or haematopoietic injury. As such, while Etv2 is dispensable for maintaining HSCs in steady states, it is required for emergency haematopoiesis.
Etv2 has been identified as a novel regulator of haematopoietic regeneration. Comprehensive understanding of the upstream regulators and downstream effectors of Etv2 in haematopoietic regeneration would be critical for fundamental understanding of haematopoietic stem cell biology, and the findings will be broadly applicable to clinical practice involving haematopoietic regenerative medicine; bone marrow transplantation, gene therapy and in-vitro HSC expansion.
最近的研究表明,造血干细胞(HSCs)在稳态条件下保持静止,并且对造血稳态的贡献最小。然而,它们在骨髓移植或造血损伤后经历广泛的细胞周期和扩增,以重建造血系统。HSC 激活和扩增的分子基础尚未完全理解。在这里,我们回顾了最近的研究,该研究阐明了发育关键 ETS 转录因子 Etv2 通过促进 HSC 再生在损伤后重建造血系统中的作用。
我们最近表明,ETS 转录因子 Etv2 是造血和血管发育的关键因子,对于造血再生也是必需的。Etv2 在稳态 HSCs 中处于沉默状态,在再生的 HSPC 中短暂激活,并且在骨髓移植或造血损伤后 HSC 扩增和再生中是必需的。因此,虽然 Etv2 对于维持 HSCs 在稳定状态下是不必要的,但它对于紧急造血是必需的。
Etv2 已被确定为造血再生的新调节因子。全面了解 Etv2 在造血再生中的上游调节因子和下游效应子对于深入了解造血干细胞生物学至关重要,并且这些发现将广泛适用于涉及造血再生医学的临床实践;骨髓移植、基因治疗和体外 HSC 扩增。