Zhou Ya, Mao Bin, Chen Yijin, Xue Yuan, Chen Bo, Zhang Yonggang, Ma Feng
Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu 610052, China.
State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC, Tianjin 300020, China.
Blood Sci. 2020 Jan 16;2(1):1-6. doi: 10.1097/BS9.0000000000000040. eCollection 2020 Jan.
GATA2, a principal member of the GATA family, plays important roles in the generation and maintenance of hematopoietic stem/progenitor cells. Among the three mRNA transcripts, the distal first exon of GATA2 (IS exon) is specific for hematopoietic and neuronal cells. GATA2 mutants with abnormal expression are often present in acute myeloid leukemia-related familial diseases and myelodysplastic syndrome, indicating the crucial significance of GATA2 in the proper maintenance of blood system functions. This article offers an overview of the regulation dynamics and function of GATA2 in the generation, proliferation, and function of hematopoietic stem cells in both mouse and human models. We acknowledge the current progress in the cell fate determination mechanism by dynamic GATA2 expression. The gene modification approaches for inspecting the role of GATA2 in definitive hematopoiesis demonstrate the potential for acquiring hPSC-derived hematopoietic stem cells via manipulated GATA2 regulation.
GATA2是GATA家族的主要成员,在造血干/祖细胞的产生和维持中发挥重要作用。在三种mRNA转录本中,GATA2的远端第一个外显子(IS外显子)对造血细胞和神经细胞具有特异性。表达异常的GATA2突变体常出现在急性髓系白血病相关的家族性疾病和骨髓增生异常综合征中,这表明GATA2在正常维持血液系统功能方面具有至关重要的意义。本文概述了GATA2在小鼠和人类模型中造血干细胞的产生、增殖和功能方面的调控动态及功能。我们认可通过动态GATA2表达在细胞命运决定机制方面取得的当前进展。用于检查GATA2在确定性造血中作用的基因编辑方法证明了通过调控GATA2获得人多能干细胞衍生的造血干细胞的潜力。