Cargando…
Nuclear transcriptome profiling of induced pluripotent stem cells and embryonic stem cells identify non-coding loci resistant to reprogramming
Identification of functionally relevant differences between induced pluripotent stem cells (iPSC) and reference embryonic stem cells (ESC) remains a central question for therapeutic applications. Differences in gene expression between iPSC and ESC have been examined by microarray and more recently w...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613594/ https://www.ncbi.nlm.nih.gov/pubmed/25664506 http://dx.doi.org/10.4161/15384101.2014.988031 |
_version_ | 1782396300964134912 |
---|---|
author | Fort, Alexandre Yamada, Daisuke Hashimoto, Kosuke Koseki, Haruhiko Carninci, Piero |
author_facet | Fort, Alexandre Yamada, Daisuke Hashimoto, Kosuke Koseki, Haruhiko Carninci, Piero |
author_sort | Fort, Alexandre |
collection | PubMed |
description | Identification of functionally relevant differences between induced pluripotent stem cells (iPSC) and reference embryonic stem cells (ESC) remains a central question for therapeutic applications. Differences in gene expression between iPSC and ESC have been examined by microarray and more recently with RNA-SEQ technologies. We here report an in depth analyses of nuclear and cytoplasmic transcriptomes, using the CAGE (cap analysis of gene expression) technology, for 5 iPSC clones derived from mouse lymphocytes B and 3 ESC lines. This approach reveals nuclear transcriptomes significantly more complex in ESC than in iPSC. Hundreds of yet not annotated putative non-coding RNAs and enhancer-associated transcripts specifically transcribed in ESC have been detected and supported with epigenetic and chromatin-chromatin interactions data. We identified super-enhancers transcriptionally active specifically in ESC and associated with genes implicated in the maintenance of pluripotency. Similarly, we detected non-coding transcripts of yet unknown function being regulated by ESC specific super-enhancers. Taken together, these results demonstrate that current protocols of iPSC reprogramming do not trigger activation of numerous cis-regulatory regions. It thus reinforces the need for already suggested deeper monitoring of the non-coding transcriptome when characterizing iPSC clones. Such differences in regulatory transcript expression may indeed impact their potential for clinical applications. |
format | Online Article Text |
id | pubmed-4613594 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-46135942016-02-03 Nuclear transcriptome profiling of induced pluripotent stem cells and embryonic stem cells identify non-coding loci resistant to reprogramming Fort, Alexandre Yamada, Daisuke Hashimoto, Kosuke Koseki, Haruhiko Carninci, Piero Cell Cycle Extra View Identification of functionally relevant differences between induced pluripotent stem cells (iPSC) and reference embryonic stem cells (ESC) remains a central question for therapeutic applications. Differences in gene expression between iPSC and ESC have been examined by microarray and more recently with RNA-SEQ technologies. We here report an in depth analyses of nuclear and cytoplasmic transcriptomes, using the CAGE (cap analysis of gene expression) technology, for 5 iPSC clones derived from mouse lymphocytes B and 3 ESC lines. This approach reveals nuclear transcriptomes significantly more complex in ESC than in iPSC. Hundreds of yet not annotated putative non-coding RNAs and enhancer-associated transcripts specifically transcribed in ESC have been detected and supported with epigenetic and chromatin-chromatin interactions data. We identified super-enhancers transcriptionally active specifically in ESC and associated with genes implicated in the maintenance of pluripotency. Similarly, we detected non-coding transcripts of yet unknown function being regulated by ESC specific super-enhancers. Taken together, these results demonstrate that current protocols of iPSC reprogramming do not trigger activation of numerous cis-regulatory regions. It thus reinforces the need for already suggested deeper monitoring of the non-coding transcriptome when characterizing iPSC clones. Such differences in regulatory transcript expression may indeed impact their potential for clinical applications. Taylor & Francis 2015-02-09 /pmc/articles/PMC4613594/ /pubmed/25664506 http://dx.doi.org/10.4161/15384101.2014.988031 Text en © 2015 The Author(s). Published with license by Taylor & Francis Group, LLC http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted. |
spellingShingle | Extra View Fort, Alexandre Yamada, Daisuke Hashimoto, Kosuke Koseki, Haruhiko Carninci, Piero Nuclear transcriptome profiling of induced pluripotent stem cells and embryonic stem cells identify non-coding loci resistant to reprogramming |
title | Nuclear transcriptome profiling of induced pluripotent stem cells and embryonic stem cells identify non-coding loci resistant to reprogramming |
title_full | Nuclear transcriptome profiling of induced pluripotent stem cells and embryonic stem cells identify non-coding loci resistant to reprogramming |
title_fullStr | Nuclear transcriptome profiling of induced pluripotent stem cells and embryonic stem cells identify non-coding loci resistant to reprogramming |
title_full_unstemmed | Nuclear transcriptome profiling of induced pluripotent stem cells and embryonic stem cells identify non-coding loci resistant to reprogramming |
title_short | Nuclear transcriptome profiling of induced pluripotent stem cells and embryonic stem cells identify non-coding loci resistant to reprogramming |
title_sort | nuclear transcriptome profiling of induced pluripotent stem cells and embryonic stem cells identify non-coding loci resistant to reprogramming |
topic | Extra View |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613594/ https://www.ncbi.nlm.nih.gov/pubmed/25664506 http://dx.doi.org/10.4161/15384101.2014.988031 |
work_keys_str_mv | AT fortalexandre nucleartranscriptomeprofilingofinducedpluripotentstemcellsandembryonicstemcellsidentifynoncodinglociresistanttoreprogramming AT yamadadaisuke nucleartranscriptomeprofilingofinducedpluripotentstemcellsandembryonicstemcellsidentifynoncodinglociresistanttoreprogramming AT hashimotokosuke nucleartranscriptomeprofilingofinducedpluripotentstemcellsandembryonicstemcellsidentifynoncodinglociresistanttoreprogramming AT kosekiharuhiko nucleartranscriptomeprofilingofinducedpluripotentstemcellsandembryonicstemcellsidentifynoncodinglociresistanttoreprogramming AT carnincipiero nucleartranscriptomeprofilingofinducedpluripotentstemcellsandembryonicstemcellsidentifynoncodinglociresistanttoreprogramming |