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Mga is essential for the survival of pluripotent cells during peri-implantation development.
Development 142, 31-40 (2015)
The maintenance and control of pluripotency is of great interest in stem cell biology. The dual specificity T-box/basic-helix-loop-helix-zipper transcription factor Mga is expressed in the pluripotent cells of the inner cell mass (ICM) and epiblast of the peri-implantation mouse embryo, but its function has not been investigated previously. Here, we use a loss-of-function allele and RNA knockdown to demonstrate that Mga depletion leads to the death of proliferating pluripotent ICM cells in vivo and in vitro, and the death of embryonic stem cells (ESCs) in vitro. Additionally, quiescent pluripotent cells lacking Mga are lost during embryonic diapause. Expression of Odc1, the rate-limiting enzyme in the conversion of ornithine into putrescine in the synthesis of polyamines, is reduced in Mga mutant cells, and the survival of mutant ICM cells as well as ESCs is rescued in culture by the addition of exogenous putrescine. These results suggest a mechanism whereby Mga influences pluripotent cell survival through regulation of the polyamine pool in pluripotent cells of the embryo, whether they are in a proliferative or quiescent state.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Basic-helix-loop-helix-zipper ; Escs ; Mga ; Mouse ; Odc ; Pluripotency ; T-box ; Transcription Factor; Embryonic Stem-cells; Ornithine-decarboxylase Gene; Early Mouse Development; C-myc Expression; Transcription Factor; Self-renewal; Polyamine Metabolism; Ground-state; Max; Network
Language
english
Publication Year
2015
HGF-reported in Year
2015
ISSN (print) / ISBN
0950-1991
e-ISSN
1477-9129
Quellenangaben
Volume: 142,
Issue: 1,
Pages: 31-40
Publisher
Company of Biologists
Publishing Place
Cambridge
Reviewing status
Peer reviewed
Institute(s)
Institute of Developmental Genetics (IDG)
POF-Topic(s)
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30204 - Cell Programming and Repair
30204 - Cell Programming and Repair
Research field(s)
Genetics and Epidemiology
PSP Element(s)
G-520600-001
G-500500-001
G-500500-001
PubMed ID
25516968
WOS ID
WOS:000348240500008
Erfassungsdatum
2015-01-05