Cargando…

Enhanced Generation of Induced Pluripotent Stem Cells from a Subpopulation of Human Fibroblasts

BACKGROUND: The derivation of induced pluripotent stem cells (iPSCs) provides new possibilities for basic research and novel cell-based therapies. Limitations, however, include our current lack of understanding regarding the underlying mechanisms and the inefficiency of reprogramming. METHODOLOGY/PR...

Descripción completa

Detalles Bibliográficos
Autores principales: Byrne, James A., Nguyen, Ha Nam, Reijo Pera, Renee A.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744017/
https://www.ncbi.nlm.nih.gov/pubmed/19774082
http://dx.doi.org/10.1371/journal.pone.0007118
_version_ 1782171891231883264
author Byrne, James A.
Nguyen, Ha Nam
Reijo Pera, Renee A.
author_facet Byrne, James A.
Nguyen, Ha Nam
Reijo Pera, Renee A.
author_sort Byrne, James A.
collection PubMed
description BACKGROUND: The derivation of induced pluripotent stem cells (iPSCs) provides new possibilities for basic research and novel cell-based therapies. Limitations, however, include our current lack of understanding regarding the underlying mechanisms and the inefficiency of reprogramming. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report identification and isolation of a subpopulation of human dermal fibroblasts that express the pluripotency marker stage specific embryonic antigen 3 (SSEA3). Fibroblasts that expressed SSEA3 demonstrated an enhanced iPSC generation efficiency, while no iPSC derivation was obtained from the fibroblasts that did not express SSEA3. Transcriptional analysis revealed NANOG expression was significantly increased in the SSEA3 expressing fibroblasts, suggesting a possible mechanistic explanation for the differential reprogramming. CONCLUSIONS/SIGNIFICANCE: To our knowledge, this study is the first to identify a pluripotency marker in a heterogeneous population of human dermal fibroblasts, to isolate a subpopulation of cells that have a significantly increased propensity to reprogram to pluripotency and to identify a possible mechanism to explain this differential reprogramming. This discovery provides a method to significantly increase the efficiency of reprogramming, enhancing the feasibility of the potential applications based on this technology, and a tool for basic research studies to understand the underlying reprogramming mechanisms.
format Text
id pubmed-2744017
institution National Center for Biotechnology Information
language English
publishDate 2009
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-27440172009-09-23 Enhanced Generation of Induced Pluripotent Stem Cells from a Subpopulation of Human Fibroblasts Byrne, James A. Nguyen, Ha Nam Reijo Pera, Renee A. PLoS One Research Article BACKGROUND: The derivation of induced pluripotent stem cells (iPSCs) provides new possibilities for basic research and novel cell-based therapies. Limitations, however, include our current lack of understanding regarding the underlying mechanisms and the inefficiency of reprogramming. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report identification and isolation of a subpopulation of human dermal fibroblasts that express the pluripotency marker stage specific embryonic antigen 3 (SSEA3). Fibroblasts that expressed SSEA3 demonstrated an enhanced iPSC generation efficiency, while no iPSC derivation was obtained from the fibroblasts that did not express SSEA3. Transcriptional analysis revealed NANOG expression was significantly increased in the SSEA3 expressing fibroblasts, suggesting a possible mechanistic explanation for the differential reprogramming. CONCLUSIONS/SIGNIFICANCE: To our knowledge, this study is the first to identify a pluripotency marker in a heterogeneous population of human dermal fibroblasts, to isolate a subpopulation of cells that have a significantly increased propensity to reprogram to pluripotency and to identify a possible mechanism to explain this differential reprogramming. This discovery provides a method to significantly increase the efficiency of reprogramming, enhancing the feasibility of the potential applications based on this technology, and a tool for basic research studies to understand the underlying reprogramming mechanisms. Public Library of Science 2009-09-23 /pmc/articles/PMC2744017/ /pubmed/19774082 http://dx.doi.org/10.1371/journal.pone.0007118 Text en Byrne et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Byrne, James A.
Nguyen, Ha Nam
Reijo Pera, Renee A.
Enhanced Generation of Induced Pluripotent Stem Cells from a Subpopulation of Human Fibroblasts
title Enhanced Generation of Induced Pluripotent Stem Cells from a Subpopulation of Human Fibroblasts
title_full Enhanced Generation of Induced Pluripotent Stem Cells from a Subpopulation of Human Fibroblasts
title_fullStr Enhanced Generation of Induced Pluripotent Stem Cells from a Subpopulation of Human Fibroblasts
title_full_unstemmed Enhanced Generation of Induced Pluripotent Stem Cells from a Subpopulation of Human Fibroblasts
title_short Enhanced Generation of Induced Pluripotent Stem Cells from a Subpopulation of Human Fibroblasts
title_sort enhanced generation of induced pluripotent stem cells from a subpopulation of human fibroblasts
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744017/
https://www.ncbi.nlm.nih.gov/pubmed/19774082
http://dx.doi.org/10.1371/journal.pone.0007118
work_keys_str_mv AT byrnejamesa enhancedgenerationofinducedpluripotentstemcellsfromasubpopulationofhumanfibroblasts
AT nguyenhanam enhancedgenerationofinducedpluripotentstemcellsfromasubpopulationofhumanfibroblasts
AT reijoperareneea enhancedgenerationofinducedpluripotentstemcellsfromasubpopulationofhumanfibroblasts