Zfx controls the self-renewal of embryonic and hematopoietic stem cells.
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.
Galan-Caridad
Jose M
JM
Department of Microbiology, Columbia University Medical Center, New York, NY 10032, USA.
Harel
Sivan
S
Arenzana
Teresita L
TL
Hou
Z Esther
ZE
Doetsch
Fiona K
FK
Mirny
Leonid A
LA
Reizis
Boris
B
D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D049109:Cell Proliferation; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D018390:Gene Targeting; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000235:genetics; D020825:T-Box Domain Proteins / Q000235:genetics
D051741:Kruppel-Like Transcription Factors; D011518:Proto-Oncogene Proteins; D020825:T-Box Domain Proteins; C491460:Tbx3 protein, mouse; C490393:Tcl1 protein, mouse; C062076:zinc finger protein, X-linked