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Failure of extra-embryonic progenitor maintenance in the absence of dosage compensation
- Publication Year :
- 2012
- Publisher :
- The University of North Carolina at Chapel Hill University Libraries, 2012.
-
Abstract
- Proper regulation of X-linked gene expression, termed dosage compensation, is required for the normal development of mammalian embryos. Through the process of X chromosome inactivation (XCI), somatic cells of mammalian females inactivate one of their two X chromosomes in order to balance X-linked gene dosage with their male counterparts. The process of XCI is dependent upon the long non-coding RNA Xist, which is expressed from and coats the inactivated X chromosome (Xi) in cis. During mouse embryogenesis, imprinted XCI inactivates the paternally inherited X chromosome (Xp) within the extra-embryonic lineages. Consequently, females harboring a paternally derived Xist mutation (X/XXist–) die owing to failure of imprinted XCI and, presumably, poor trophoblast development. Here, we investigate the consequence of two active X chromosomes in the extra-embryonic ectoderm (ExE) of X/XXist– female embryos. At embryonic day (E) 6.5, we find that the X/XXist– ExE lacks the transcriptional regulator CDX2, a factor required to maintain the ExE in a progenitor state. In addition, spongiotrophoblast progenitors are not maintained. Surprisingly, we observe evidence of an Xi in a subpopulation of X/XXist– ExE cells. We demonstrate further that trophectodermal stem cells derived from X/XXist– embryos completely reverse normal imprinted XCI patterns. Taken together, our data suggest that, much like in the cells of the epiblast, the initial imprint that establishes imprinted XCI is probably erased in ExE cells. Conversely, unlike the epiblast, in which XCI is not required for progenitor cell maintenance, we demonstrate that dosage compensation is indispensable for the maintenance of trophoblast progenitors.
- Subjects :
- Male
RNA, Untranslated
X Chromosome
Extraembryonic Membranes
Cell Count
Biology
X-inactivation
Genomic Imprinting
Mice
X Chromosome Inactivation
Dosage Compensation, Genetic
Ectoderm
Animals
CDX2 Transcription Factor
Progenitor cell
Molecular Biology
Embryonic Stem Cells
X chromosome
Homeodomain Proteins
Dosage compensation
Development and Stem Cells
Molecular biology
Trophoblasts
Blastocyst
Epiblast
embryonic structures
Female
RNA, Long Noncoding
XIST
Stem cell
Genomic imprinting
Transcription Factors
Developmental Biology
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....4f553870e183d37a9d46900e5d8b74f7
- Full Text :
- https://doi.org/10.17615/mrhp-7z61