Nuclear Transfer‐Derived Epiblast Stem Cells Are Transcriptionally and Epigenetically Distinguishable from Their Fertilized‐Derived Counterparts
Mouse embryonic pluripotent stem cells can be obtained from the inner cell mass at the blastocyst stage (embryonic stem cells, ESCs) or from the late epiblast of postimplantation embryos (epiblast stem cells, EpiSCs). During normal development, the transition between these two stages is marked by ma...
Saved in:
| Published in: | Stem cells (Dayton, Ohio) Vol. 28; no. 4; pp. 743 - 752 |
|---|---|
| Main Authors: | , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
01-04-2010
AlphaMed Press |
| Subjects: | |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Mouse embryonic pluripotent stem cells can be obtained from the inner cell mass at the blastocyst stage (embryonic stem cells, ESCs) or from the late epiblast of postimplantation embryos (epiblast stem cells, EpiSCs). During normal development, the transition between these two stages is marked by major epigenetic and transcriptional changes including DNA de novo methylation. These modifications represent an epigenetic mark conserved in ESCs and EpiSCs. Pluripotent ESCs derived from blastocysts generated by nuclear transfer (NT) have been shown to be correctly reprogrammed. However, NT embryos frequently undergo abnormal development. In the present study, we have examined whether pluripotent cells could be derived from the epiblast of postimplantation NT embryos and whether the reprogramming process would affect the epigenetic changes occurring at this stage, which could explain abnormal development of NT embryos. We showed that EpiSCs could be derived with the same efficiency from NT embryos and from their fertilized counterparts. However, gene expression profile analyses showed divergence between fertilized‐ and nuclear transfer‐EpiSCs with a surprising bias in the distribution of the differentially expressed genes, 30% of them being localized on chromosome 11. A majority of these genes were downregulated in NT‐EpiSCs and imprinted genes represented a significant fraction of them. Notably, analysis of the epigenetic status of a downregulated imprinted gene in NT‐EpiSCs revealed complete methylation of the two alleles. Therefore, EpiSCs derived from NT embryos appear to be incorrectly reprogrammed, indicating that abnormal epigenetic marks are imposed on cells in NT embryos during the transition from early to late epiblast. STEM CELLS 2010;28:743–75228:743–752 |
|---|---|
| Bibliography: | First published online in STEM CELLS J.M.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing; X.P.D. and V.B.: provision of study material; J.M. and X.P.D.: contributed equally to this work; L.J. and J.L.: data analysis and interpretation; A.B.: karyotype analysis; H.J.: bisulfite conversion and sequence analysis; L.V.: conception and design, text editing; I.G.M.B. and R.P.: help with EpiSC derivation, scientific advice; Q.Z.: financial and administrative support, scientific advice; J.R.: financial and administrative support, data analysis and interpretation, manuscript writing, final approval of manuscript; A.J.: conception and design, data analysis and interpretation, manuscript writing, final approval of manuscript. Disclosure of potential conflicts of interest is found at the end of this article. Telephone: 86‐10‐64807050; Fax: 86‐10‐64807316 Telephone: 33 1 34 65 25 68; Fax: 33 1 34 65 23 64 EXPRESS February 16, 2010. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ISSN: | 1066-5099 1549-4918 |
| DOI: | 10.1002/stem.400 |