Kyunghee Choi1,2. 1. Department of Pathology and Immunology, Developmental, Regenerative, and Stem Cell Biology Program, Washington University School of Medicine, St. Louis, Missouri, USA. 2. Graduate School of Biotechnology, Kyung Hee University, Yong In, South Korea.
Abstract
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: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.