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血细胞发生的转录控制。

Transcriptional control of blood cell emergence.

机构信息

Developmental Haematopoiesis Group, Faculty of Biology, Medicine and Health, the University of Manchester, UK.

Cancer Research UK Stem Cell Biology Group, Cancer Research UK Manchester Institute, The University of Manchester, Macclesfield, UK.

出版信息

FEBS Lett. 2019 Dec;593(23):3304-3315. doi: 10.1002/1873-3468.13585. Epub 2019 Aug 31.

Abstract

The haematopoietic system is established during embryonic life through a series of developmental steps that culminates with the generation of haematopoietic stem cells. Characterisation of the transcriptional network that regulates blood cell emergence has led to the identification of transcription factors essential for this process. Among the many factors wired within this complex regulatory network, ETV2, SCL and RUNX1 are the central components. All three factors are absolutely required for blood cell generation, each one controlling a precise step of specification from the mesoderm germ layer to fully functional blood progenitors. Insight into the transcriptional control of blood cell emergence has been used for devising protocols to generate blood cells de novo, either through reprogramming of somatic cells or through forward programming of pluripotent stem cells. Interestingly, the physiological process of blood cell generation and its laboratory-engineered counterpart have very little in common.

摘要

造血系统是在胚胎期通过一系列发育步骤建立的,最终产生造血干细胞。对调节血细胞发生的转录网络的特征描述导致了对这个过程至关重要的转录因子的鉴定。在这个复杂的调控网络中,有许多因素相互关联,其中 ETV2、SCL 和 RUNX1 是核心成分。这三个因素对于血细胞的生成都是绝对必需的,它们各自控制着从中胚层到完全功能性的造血祖细胞的精确分化步骤。对血细胞发生的转录控制的深入了解已被用于设计从头生成血细胞的方案,无论是通过体细胞重编程还是通过多能干细胞的正向编程。有趣的是,血细胞生成的生理过程及其在实验室中的工程化对应物几乎没有共同之处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97de/6916194/98a7a87272cb/FEB2-593-3304-g001.jpg

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