Epigenetic Induction of Definitive and Pancreatic Endoderm Cell Fate in Human Fibroblasts
Reprogramming can occur by the introduction of key transcription factors (TFs) as well as by epigenetic changes. We demonstrated that histone deacetylase inhibitor (HDACi) Trichostatin A (TSA) combined with a chromatin remodeling medium (CRM) induced expression of a number of definitive endoderm and...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2016/7654321 |
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| author | Rangarajan Sambathkumar Eric Kalo Rob Van Rossom Marijke M. Faas Paul de Vos Catherine M. Verfaillie |
| author_facet | Rangarajan Sambathkumar Eric Kalo Rob Van Rossom Marijke M. Faas Paul de Vos Catherine M. Verfaillie |
| author_sort | Rangarajan Sambathkumar |
| collection | DOAJ |
| description | Reprogramming can occur by the introduction of key transcription factors (TFs) as well as by epigenetic changes. We demonstrated that histone deacetylase inhibitor (HDACi) Trichostatin A (TSA) combined with a chromatin remodeling medium (CRM) induced expression of a number of definitive endoderm and early and late pancreatic marker genes. When CRM was omitted, endoderm/pancreatic marker genes were not induced. Furthermore, treatment with DNA methyltransferase inhibitor (DNMTi) 5-azacytidine (5AZA) CRM did not affect gene expression changes, and when 5AZA was combined with TSA, no further increase in gene expression of endoderm, pancreatic endoderm, and endocrine markers was seen over levels induced with TSA alone. Interestingly, TSA-CRM did not affect expression of pluripotency and hepatocyte genes but induced some mesoderm transcripts. Upon removal of TSA-CRM, the endoderm/pancreatic gene expression profile returned to baseline. Our findings underscore the role epigenetic modification in transdifferentiation of one somatic cell into another. However, full reprogramming of fibroblasts to β-cells will require combination of this approach with TF overexpression and/or culture of the partially reprogrammed cells under β-cell specific conditions. |
| format | Article |
| id | doaj-art-11afa75483f24e8a849c760038c61e1c |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-11afa75483f24e8a849c760038c61e1c2025-02-03T01:32:40ZengWileyStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/76543217654321Epigenetic Induction of Definitive and Pancreatic Endoderm Cell Fate in Human FibroblastsRangarajan Sambathkumar0Eric Kalo1Rob Van Rossom2Marijke M. Faas3Paul de Vos4Catherine M. Verfaillie5Interdepartmental Stem Cell Institute, Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven, 3000 Leuven, BelgiumInterdepartmental Stem Cell Institute, Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven, 3000 Leuven, BelgiumInterdepartmental Stem Cell Institute, Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven, 3000 Leuven, BelgiumUniversity Medical Center Groningen (UMCG), Pathology and Medical Biology, Section of Immunoendocrinology, University of Groningen, Hanzeplein 1, EA 11, 9713 GZ Groningen, NetherlandsUniversity Medical Center Groningen (UMCG), Pathology and Medical Biology, Section of Immunoendocrinology, University of Groningen, Hanzeplein 1, EA 11, 9713 GZ Groningen, NetherlandsInterdepartmental Stem Cell Institute, Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven, 3000 Leuven, BelgiumReprogramming can occur by the introduction of key transcription factors (TFs) as well as by epigenetic changes. We demonstrated that histone deacetylase inhibitor (HDACi) Trichostatin A (TSA) combined with a chromatin remodeling medium (CRM) induced expression of a number of definitive endoderm and early and late pancreatic marker genes. When CRM was omitted, endoderm/pancreatic marker genes were not induced. Furthermore, treatment with DNA methyltransferase inhibitor (DNMTi) 5-azacytidine (5AZA) CRM did not affect gene expression changes, and when 5AZA was combined with TSA, no further increase in gene expression of endoderm, pancreatic endoderm, and endocrine markers was seen over levels induced with TSA alone. Interestingly, TSA-CRM did not affect expression of pluripotency and hepatocyte genes but induced some mesoderm transcripts. Upon removal of TSA-CRM, the endoderm/pancreatic gene expression profile returned to baseline. Our findings underscore the role epigenetic modification in transdifferentiation of one somatic cell into another. However, full reprogramming of fibroblasts to β-cells will require combination of this approach with TF overexpression and/or culture of the partially reprogrammed cells under β-cell specific conditions.http://dx.doi.org/10.1155/2016/7654321 |
| spellingShingle | Rangarajan Sambathkumar Eric Kalo Rob Van Rossom Marijke M. Faas Paul de Vos Catherine M. Verfaillie Epigenetic Induction of Definitive and Pancreatic Endoderm Cell Fate in Human Fibroblasts Stem Cells International |
| title | Epigenetic Induction of Definitive and Pancreatic Endoderm Cell Fate in Human Fibroblasts |
| title_full | Epigenetic Induction of Definitive and Pancreatic Endoderm Cell Fate in Human Fibroblasts |
| title_fullStr | Epigenetic Induction of Definitive and Pancreatic Endoderm Cell Fate in Human Fibroblasts |
| title_full_unstemmed | Epigenetic Induction of Definitive and Pancreatic Endoderm Cell Fate in Human Fibroblasts |
| title_short | Epigenetic Induction of Definitive and Pancreatic Endoderm Cell Fate in Human Fibroblasts |
| title_sort | epigenetic induction of definitive and pancreatic endoderm cell fate in human fibroblasts |
| url | http://dx.doi.org/10.1155/2016/7654321 |
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