Epigenetic and phenotypic profile of fibroblasts derived from induced pluripotent stem cells.

Human induced pluripotent stem (hiPS) cells offer a novel source of patient-specific cells for regenerative medicine. However, the biological potential of iPS-derived cells and their similarities to cells differentiated from human embryonic stem (hES) cells remain unclear. We derived fibroblast-like...

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Autores principales: Kyle J Hewitt, Yulia Shamis, Ryan B Hayman, Mariam Margvelashvili, Shumin Dong, Mark W Carlson, Jonathan A Garlick
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Publicado: Public Library of Science (PLoS) 2011
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Acceso en línea:https://doaj.org/article/2a7cb5367ce34251aacea31d4b8a9af2
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spelling oai:doaj.org-article:2a7cb5367ce34251aacea31d4b8a9af22021-11-18T06:58:08ZEpigenetic and phenotypic profile of fibroblasts derived from induced pluripotent stem cells.1932-620310.1371/journal.pone.0017128https://doaj.org/article/2a7cb5367ce34251aacea31d4b8a9af22011-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21386890/?tool=EBIhttps://doaj.org/toc/1932-6203Human induced pluripotent stem (hiPS) cells offer a novel source of patient-specific cells for regenerative medicine. However, the biological potential of iPS-derived cells and their similarities to cells differentiated from human embryonic stem (hES) cells remain unclear. We derived fibroblast-like cells from two hiPS cell lines and show that their phenotypic properties and patterns of DNA methylation were similar to that of mature fibroblasts and to fibroblasts derived from hES cells. iPS-derived fibroblasts (iPDK) and their hES-derived counterparts (EDK) showed similar cell morphology throughout differentiation, and patterns of gene expression and cell surface markers were characteristic of mature fibroblasts. Array-based methylation analysis was performed for EDK, iPDK and their parental hES and iPS cell lines, and hierarchical clustering revealed that EDK and iPDK had closely-related methylation profiles. DNA methylation analysis of promoter regions associated with extracellular matrix (ECM)-production (COL1A1) by iPS- and hESC-derived fibroblasts and fibroblast lineage commitment (PDGFRβ), revealed promoter demethylation linked to their expression, and patterns of transcription and methylation of genes related to the functional properties of mature stromal cells were seen in both hiPS- and hES-derived fibroblasts. iPDK cells also showed functional properties analogous to those of hES-derived and mature fibroblasts, as seen by their capacity to direct the morphogenesis of engineered human skin equivalents. Characterization of the functional behavior of ES- and iPS-derived fibroblasts in engineered 3D tissues demonstrates the utility of this tissue platform to predict the capacity of iPS-derived cells before their therapeutic application.Kyle J HewittYulia ShamisRyan B HaymanMariam MargvelashviliShumin DongMark W CarlsonJonathan A GarlickPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 2, p e17128 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Kyle J Hewitt
Yulia Shamis
Ryan B Hayman
Mariam Margvelashvili
Shumin Dong
Mark W Carlson
Jonathan A Garlick
Epigenetic and phenotypic profile of fibroblasts derived from induced pluripotent stem cells.
description Human induced pluripotent stem (hiPS) cells offer a novel source of patient-specific cells for regenerative medicine. However, the biological potential of iPS-derived cells and their similarities to cells differentiated from human embryonic stem (hES) cells remain unclear. We derived fibroblast-like cells from two hiPS cell lines and show that their phenotypic properties and patterns of DNA methylation were similar to that of mature fibroblasts and to fibroblasts derived from hES cells. iPS-derived fibroblasts (iPDK) and their hES-derived counterparts (EDK) showed similar cell morphology throughout differentiation, and patterns of gene expression and cell surface markers were characteristic of mature fibroblasts. Array-based methylation analysis was performed for EDK, iPDK and their parental hES and iPS cell lines, and hierarchical clustering revealed that EDK and iPDK had closely-related methylation profiles. DNA methylation analysis of promoter regions associated with extracellular matrix (ECM)-production (COL1A1) by iPS- and hESC-derived fibroblasts and fibroblast lineage commitment (PDGFRβ), revealed promoter demethylation linked to their expression, and patterns of transcription and methylation of genes related to the functional properties of mature stromal cells were seen in both hiPS- and hES-derived fibroblasts. iPDK cells also showed functional properties analogous to those of hES-derived and mature fibroblasts, as seen by their capacity to direct the morphogenesis of engineered human skin equivalents. Characterization of the functional behavior of ES- and iPS-derived fibroblasts in engineered 3D tissues demonstrates the utility of this tissue platform to predict the capacity of iPS-derived cells before their therapeutic application.
format article
author Kyle J Hewitt
Yulia Shamis
Ryan B Hayman
Mariam Margvelashvili
Shumin Dong
Mark W Carlson
Jonathan A Garlick
author_facet Kyle J Hewitt
Yulia Shamis
Ryan B Hayman
Mariam Margvelashvili
Shumin Dong
Mark W Carlson
Jonathan A Garlick
author_sort Kyle J Hewitt
title Epigenetic and phenotypic profile of fibroblasts derived from induced pluripotent stem cells.
title_short Epigenetic and phenotypic profile of fibroblasts derived from induced pluripotent stem cells.
title_full Epigenetic and phenotypic profile of fibroblasts derived from induced pluripotent stem cells.
title_fullStr Epigenetic and phenotypic profile of fibroblasts derived from induced pluripotent stem cells.
title_full_unstemmed Epigenetic and phenotypic profile of fibroblasts derived from induced pluripotent stem cells.
title_sort epigenetic and phenotypic profile of fibroblasts derived from induced pluripotent stem cells.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/2a7cb5367ce34251aacea31d4b8a9af2
work_keys_str_mv AT kylejhewitt epigeneticandphenotypicprofileoffibroblastsderivedfrominducedpluripotentstemcells
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