Developmental Potential of Gcn5(-/-) Embryonic Stem Cells in Vivo and in Vitro.
From: Program in Genes and Development, Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
Developmental dynamics : an official publication of the American Association of Anatomists
- Publish Date: Jun 2007
- ISSN: 1058-8388
- Volume: 236
- Issue: 6
- Pages: 1547-57
- Medium: Print
- Language: English
- Citation (JAMA): Lin Wenchu, Srajer Geraldine, Evrard Yvonne A, et al. Developmental Potential of Gcn5(-/-) Embryonic Stem Cells in Vivo and in Vitro.. Dev. Dyn. Jun 2007;236:1547-57
Abstract
Gcn5 is a prototypical histone acetyltransferase (HAT) that serves as a coactivator for multiple DNA-bound transcription factors. We previously determined that deletion of Gcn512 (hereafter referred to as Gcn5) causes embryonic lethality in mice. Gcn5 null embryos undergo gastrulation but exhibit high levels of apoptosis, leading to loss of mesodermal lineages. To further define the functions of Gcn5 during development, we created Gcn5(-/-) mouse embryonic stem (ES) cells. These cells survived in vitro and formed embryoid bodies (EBs) that expressed markers for ectodermal, mesodermal, and endodermal lineages. Gcn5(-/-) EBs were misshapen and smaller than wild-type EBs by day 6, with an increased proportion of cells in G2/M. Expression of Oct 4 and Nodal was prematurely curtailed in Gcn5(-/-) EBs, indicating early loss of pluripotent ES cells. Gcn5(-/-) EBs differentiated efficiently into skeletal and cardiac muscle, which derive from mesoderm. High percentage Gcn5(-/-) chimeric embryos created by injection of Gcn5(-/-) ES cells into wild-type blastocysts were delayed in development and died early. Interestingly, elevated levels of apoptosis were observed specifically in Gcn5 null cells within the chimeric embryos. Collectively, these data indicate that Gcn5 may be required to maintain pluripotent states and that loss of Gcn5 invokes a cell-autonomous pathway of cell death in vivo.
Mesh Headings (Keywords): Acetylation, Animals, Apoptosis, Cell Cycle Proteins, Cell Differentiation, Cell Lineage, Cells, Cultured, Embryo, Mammalian, Embryonic Stem Cells, Gene Expression Regulation, Developmental, Histone Acetyltransferases, Mice, Mice, Inbred C57BL, Mice, Knockout, Muscle, Skeletal, Proteins, Transcription Factors, p300-CBP Transcription Factors
Check for Full Text / PubMed Unique Identifier (PMID): 17440986
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