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 Zf...

Full description

Saved in:
Bibliographic Details
Published in:Cell 2007-04, Vol.129 (2), p.345-357
Main Authors: Galan-Caridad, Jose M., Harel, Sivan, Arenzana, Teresita L., Hou, Z. Esther, Doetsch, Fiona K., Mirny, Leonid A., Reizis, Boris
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Cell Differentiation
Cell Proliferation
Embryonic Stem Cells - cytology
Embryonic Stem Cells - metabolism
Female
Gene Expression
Gene Targeting
Hematopoietic Stem Cells - cytology
Hematopoietic Stem Cells - metabolism
Kruppel-Like Transcription Factors - genetics
Kruppel-Like Transcription Factors - metabolism
Male
Mice
Proto-Oncogene Proteins - genetics
T-Box Domain Proteins - genetics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2007.03.014