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Pancreatic Progenitor Commitment Is Marked by an Increase in Ink4a/Arf Expression

The identification of the molecular mechanisms controlling early cell fate decisions in mammals is of paramount importance as the ability to determine specific lineage differentiation represents a significant opportunity for new therapies. Pancreatic Progenitor Cells (PPCs) constitute a regenerative...

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Autores principales: Montano, Elena, Pollice, Alessandra, Lucci, Valeria, Falco, Geppino, Affinito, Ornella, La Mantia, Girolama, Vivo, Maria, Angrisano, Tiziana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392192/
https://www.ncbi.nlm.nih.gov/pubmed/34439790
http://dx.doi.org/10.3390/biom11081124
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author Montano, Elena
Pollice, Alessandra
Lucci, Valeria
Falco, Geppino
Affinito, Ornella
La Mantia, Girolama
Vivo, Maria
Angrisano, Tiziana
author_facet Montano, Elena
Pollice, Alessandra
Lucci, Valeria
Falco, Geppino
Affinito, Ornella
La Mantia, Girolama
Vivo, Maria
Angrisano, Tiziana
author_sort Montano, Elena
collection PubMed
description The identification of the molecular mechanisms controlling early cell fate decisions in mammals is of paramount importance as the ability to determine specific lineage differentiation represents a significant opportunity for new therapies. Pancreatic Progenitor Cells (PPCs) constitute a regenerative reserve essential for the maintenance and regeneration of the pancreas. Besides, PPCs represent an excellent model for understanding pathological pancreatic cellular remodeling. Given the lack of valid markers of early endoderm, the identification of new ones is of fundamental importance. Both products of the Ink4a/Arf locus, in addition to being critical cell-cycle regulators, appear to be involved in several disease pathologies. Moreover, the locus’ expression is epigenetically regulated in ES reprogramming processes, thus constituting the ideal candidates to modulate PPCs homeostasis. In this study, starting from mouse embryonic stem cells (mESCs), we analyzed the early stages of pancreatic commitment. By inducing mESCs commitment to the pancreatic lineage, we observed that both products of the Cdkn2a locus, Ink4a and Arf, mark a naïve pancreatic cellular state that resembled PPC-like specification. Treatment with epi-drugs suggests a role for chromatin remodeling in the CDKN2a (Cycline Dependent Kinase Inhibitor 2A) locus regulation in line with previous observations in other cellular systems. Our data considerably improve the comprehension of pancreatic cellular ontogeny, which could be critical for implementing pluripotent stem cells programming and reprogramming toward pancreatic lineage commitment.
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spelling pubmed-83921922021-08-28 Pancreatic Progenitor Commitment Is Marked by an Increase in Ink4a/Arf Expression Montano, Elena Pollice, Alessandra Lucci, Valeria Falco, Geppino Affinito, Ornella La Mantia, Girolama Vivo, Maria Angrisano, Tiziana Biomolecules Article The identification of the molecular mechanisms controlling early cell fate decisions in mammals is of paramount importance as the ability to determine specific lineage differentiation represents a significant opportunity for new therapies. Pancreatic Progenitor Cells (PPCs) constitute a regenerative reserve essential for the maintenance and regeneration of the pancreas. Besides, PPCs represent an excellent model for understanding pathological pancreatic cellular remodeling. Given the lack of valid markers of early endoderm, the identification of new ones is of fundamental importance. Both products of the Ink4a/Arf locus, in addition to being critical cell-cycle regulators, appear to be involved in several disease pathologies. Moreover, the locus’ expression is epigenetically regulated in ES reprogramming processes, thus constituting the ideal candidates to modulate PPCs homeostasis. In this study, starting from mouse embryonic stem cells (mESCs), we analyzed the early stages of pancreatic commitment. By inducing mESCs commitment to the pancreatic lineage, we observed that both products of the Cdkn2a locus, Ink4a and Arf, mark a naïve pancreatic cellular state that resembled PPC-like specification. Treatment with epi-drugs suggests a role for chromatin remodeling in the CDKN2a (Cycline Dependent Kinase Inhibitor 2A) locus regulation in line with previous observations in other cellular systems. Our data considerably improve the comprehension of pancreatic cellular ontogeny, which could be critical for implementing pluripotent stem cells programming and reprogramming toward pancreatic lineage commitment. MDPI 2021-07-30 /pmc/articles/PMC8392192/ /pubmed/34439790 http://dx.doi.org/10.3390/biom11081124 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Montano, Elena
Pollice, Alessandra
Lucci, Valeria
Falco, Geppino
Affinito, Ornella
La Mantia, Girolama
Vivo, Maria
Angrisano, Tiziana
Pancreatic Progenitor Commitment Is Marked by an Increase in Ink4a/Arf Expression
title Pancreatic Progenitor Commitment Is Marked by an Increase in Ink4a/Arf Expression
title_full Pancreatic Progenitor Commitment Is Marked by an Increase in Ink4a/Arf Expression
title_fullStr Pancreatic Progenitor Commitment Is Marked by an Increase in Ink4a/Arf Expression
title_full_unstemmed Pancreatic Progenitor Commitment Is Marked by an Increase in Ink4a/Arf Expression
title_short Pancreatic Progenitor Commitment Is Marked by an Increase in Ink4a/Arf Expression
title_sort pancreatic progenitor commitment is marked by an increase in ink4a/arf expression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392192/
https://www.ncbi.nlm.nih.gov/pubmed/34439790
http://dx.doi.org/10.3390/biom11081124
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