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Highly rapid and efficient conversion of human fibroblasts to keratinocyte like cells

Cell fate commitment during development is achieved through the expression of lineage specific transcription factors. Recent studies have suggested that expression of combinations of these lineage specific transcription factors can convert adult somatic cells from one type to another. Here we report...

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Detalles Bibliográficos
Autores principales: Chen, Yifang, Mistry, Devendra S., Sen, George L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3875612/
https://www.ncbi.nlm.nih.gov/pubmed/23921950
http://dx.doi.org/10.1038/jid.2013.327
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author Chen, Yifang
Mistry, Devendra S.
Sen, George L.
author_facet Chen, Yifang
Mistry, Devendra S.
Sen, George L.
author_sort Chen, Yifang
collection PubMed
description Cell fate commitment during development is achieved through the expression of lineage specific transcription factors. Recent studies have suggested that expression of combinations of these lineage specific transcription factors can convert adult somatic cells from one type to another. Here we report that the combination of p63, a master regulator of epidermal development and differentiation, and KLF4, a regulator of epidermal differentiation is sufficient to convert dermal fibroblasts to a keratinocyte phenotype. Induced keratinocytes expressed keratinocyte specific proteins and had a transcriptome similar to keratinocytes. Reprogramming to a keratinocyte phenotype was rapid and efficient with a vast majority of cells morphologically resembling and expressing keratinocyte specific genes within a week of p63 and KLF4 transduction. Furthermore, p63 and KLF4 are capable of inducing a keratinocyte phenotype even in a cancerous cell line highlighting their importance for epidermal specification. The robustness of the conversion process also allows the use of this as a model system to study the mechanisms of reprogramming.
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spelling pubmed-38756122014-08-01 Highly rapid and efficient conversion of human fibroblasts to keratinocyte like cells Chen, Yifang Mistry, Devendra S. Sen, George L. J Invest Dermatol Article Cell fate commitment during development is achieved through the expression of lineage specific transcription factors. Recent studies have suggested that expression of combinations of these lineage specific transcription factors can convert adult somatic cells from one type to another. Here we report that the combination of p63, a master regulator of epidermal development and differentiation, and KLF4, a regulator of epidermal differentiation is sufficient to convert dermal fibroblasts to a keratinocyte phenotype. Induced keratinocytes expressed keratinocyte specific proteins and had a transcriptome similar to keratinocytes. Reprogramming to a keratinocyte phenotype was rapid and efficient with a vast majority of cells morphologically resembling and expressing keratinocyte specific genes within a week of p63 and KLF4 transduction. Furthermore, p63 and KLF4 are capable of inducing a keratinocyte phenotype even in a cancerous cell line highlighting their importance for epidermal specification. The robustness of the conversion process also allows the use of this as a model system to study the mechanisms of reprogramming. 2013-08-06 2014-02 /pmc/articles/PMC3875612/ /pubmed/23921950 http://dx.doi.org/10.1038/jid.2013.327 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Chen, Yifang
Mistry, Devendra S.
Sen, George L.
Highly rapid and efficient conversion of human fibroblasts to keratinocyte like cells
title Highly rapid and efficient conversion of human fibroblasts to keratinocyte like cells
title_full Highly rapid and efficient conversion of human fibroblasts to keratinocyte like cells
title_fullStr Highly rapid and efficient conversion of human fibroblasts to keratinocyte like cells
title_full_unstemmed Highly rapid and efficient conversion of human fibroblasts to keratinocyte like cells
title_short Highly rapid and efficient conversion of human fibroblasts to keratinocyte like cells
title_sort highly rapid and efficient conversion of human fibroblasts to keratinocyte like cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3875612/
https://www.ncbi.nlm.nih.gov/pubmed/23921950
http://dx.doi.org/10.1038/jid.2013.327
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