Sambathkumar, Rangarajan, Kalo, Eric, Van Rossom, Rob, Faas, Marijke M., de Vos, Paul, and Verfaillie, Catherine M. (2016) Epigenetic Induction of Definitive and Pancreatic Endoderm Cell Fate in Human Fibroblasts. Stem Cells International, 2016. 7654321.

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Abstract

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.

Item ID:	86145
Item Type:	Article (Research - C1)
ISSN:	1687-9678
Related URLs:	https://onlinelibrary.wiley.com/doi/epdf...
Copyright Information:	Copyright © 2016 Rangarajan Sambathkumar et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Additional Information:	Rangarajan Sambathkumar and Eric Kalo contributed equally as co-first authors in this work (R. Sambathkumar and E. Kalo et al.)
Date Deposited:	16 Jul 2025 23:38
FoR Codes:	32 BIOMEDICAL AND CLINICAL SCIENCES > 3206 Medical biotechnology > 320606 Regenerative medicine (incl. stem cells) @ 60% 32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320208 Endocrinology @ 40%
SEO Codes:	20 HEALTH > 2001 Clinical health > 200105 Treatment of human diseases and conditions @ 100%
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