Galan-Caridad Jose M, Harel Sivan, Arenzana Teresita L, Hou Z Esther, Doetsch Fiona K, Mirny Leonid A, Reizis Boris
Department of Microbiology, Columbia University Medical Center, New York, NY 10032, USA.
Cell. 2007 Apr 20;129(2):345-57. doi: 10.1016/j.cell.2007.03.014.
Stem cells (SC) exhibit a unique capacity for self-renewal in an undifferentiated state. It is unclear whether the self-renewal of pluripotent embryonic SC (ESC) and of tissue-specific adult SC such as hematopoietic SC (HSC) is controlled by common mechanisms. The deletion of transcription factor Zfx impaired the self-renewal but not the differentiation capacity of murine ESC; conversely, Zfx overexpression facilitated ESC self-renewal by opposing differentiation. Furthermore, Zfx deletion abolished the maintenance of adult HSC but did not affect erythromyeloid progenitors or fetal HSC. Zfx-deficient ESC and HSC showed increased apoptosis and SC-specific upregulation of stress-inducible genes. Zfx directly activated common target genes in ESC and HSC, as well as ESC-specific target genes including ESC self-renewal regulators Tbx3 and Tcl1. These studies identify Zfx as a shared transcriptional regulator of ESC and HSC, suggesting a common genetic basis of self-renewal in embryonic and adult SC.
干细胞（SC）在未分化状态下表现出独特的自我更新能力。目前尚不清楚多能胚胎干细胞（ESC）和组织特异性成体干细胞（如造血干细胞（HSC））的自我更新是否受共同机制控制。转录因子Zfx的缺失损害了小鼠ESC的自我更新能力，但不影响其分化能力；相反，Zfx过表达通过对抗分化促进了ESC的自我更新。此外，Zfx缺失消除了成体HSC的维持，但不影响红系髓系祖细胞或胎儿HSC。Zfx缺陷的ESC和HSC显示出凋亡增加以及应激诱导基因的SC特异性上调。Zfx直接激活ESC和HSC中的共同靶基因，以及包括ESC自我更新调节因子Tbx3和Tcl1在内的ESC特异性靶基因。这些研究确定Zfx为ESC和HSC的共同转录调节因子，提示胚胎和成体干细胞自我更新存在共同的遗传基础。
