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Pancreatic Progenitor Commitment Is Marked by an Increase in Ink4a/Arf Expression
- Source :
- Biomolecules, Vol 11, Iss 1124, p 1124 (2021), Biomolecules, Volume 11, Issue 8
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Gene Expression
Biochemistry
Epigenesis, Genetic
Mice
0302 clinical medicine
Insulin-Secreting Cells
Induced pluripotent stem cell
ARF
Cell Differentiation
Mouse Embryonic Stem Cells
Nanog Homeobox Protein
embryonic stem cells
QR1-502
Cell biology
Hepatocyte Nuclear Factor 6
medicine.anatomical_structure
030220 oncology & carcinogenesis
Hepatocyte Nuclear Factor 3-beta
Intercellular Signaling Peptides and Proteins
Pancreas
Reprogramming
Cdkn2a
Embryonic stem cells
INK4a
Pancreatic Progenitor Cells
Animals
Biomarkers
Cell Lineage
Cyclin-Dependent Kinase Inhibitor p16
Genetic Loci
Homeodomain Proteins
Octamer Transcription Factor-3
Primary Cell Culture
Trans-Activators
Cell fate determination
Biology
Microbiology
Chromatin remodeling
Article
03 medical and health sciences
Genetic
medicine
Progenitor cell
Molecular Biology
Regeneration (biology)
Embryonic stem cell
030104 developmental biology
Epigenesis
Subjects
Details
- Language :
- English
- Volume :
- 11
- Issue :
- 1124
- Database :
- OpenAIRE
- Journal :
- Biomolecules
- Accession number :
- edsair.doi.dedup.....3dde5e82bc083ae5bc7beec094850426