PDX1 is the cornerstone of pancreatic β-cell functions and identity
Diabetes has been a worldwide healthcare problem for many years. Current methods of treating diabetes are still largely directed at symptoms, aiming to control the manifestations of the pathology. This creates an overall need to find alternative measures that can impact on the causes of the disease,...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2022.1091757/full |
| _version_ | 1811183953406590976 |
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| author | Nour Ebrahim Nour Ebrahim Ksenia Shakirova Erdem Dashinimaev Erdem Dashinimaev |
| author_facet | Nour Ebrahim Nour Ebrahim Ksenia Shakirova Erdem Dashinimaev Erdem Dashinimaev |
| author_sort | Nour Ebrahim |
| collection | DOAJ |
| description | Diabetes has been a worldwide healthcare problem for many years. Current methods of treating diabetes are still largely directed at symptoms, aiming to control the manifestations of the pathology. This creates an overall need to find alternative measures that can impact on the causes of the disease, reverse diabetes, or make it more manageable. Understanding the role of key players in the pathogenesis of diabetes and the related β-cell functions is of great importance in combating diabetes. PDX1 is a master regulator in pancreas organogenesis, the maturation and identity preservation of β-cells, and of their role in normal insulin function. Mutations in the PDX1 gene are correlated with many pancreatic dysfunctions, including pancreatic agenesis (homozygous mutation) and MODY4 (heterozygous mutation), while in other types of diabetes, PDX1 expression is reduced. Therefore, alternative approaches to treat diabetes largely depend on knowledge of PDX1 regulation, its interaction with other transcription factors, and its role in obtaining β-cells through differentiation and transdifferentiation protocols. In this article, we review the basic functions of PDX1 and its regulation by genetic and epigenetic factors. Lastly, we summarize different variations of the differentiation protocols used to obtain β-cells from alternative cell sources, using PDX1 alone or in combination with various transcription factors and modified culture conditions. This review shows the unique position of PDX1 as a potential target in the genetic and cellular treatment of diabetes. |
| first_indexed | 2024-04-11T13:06:27Z |
| format | Article |
| id | doaj.art-bf212a89d20e468b8a5eed05f8efa9ca |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-04-11T13:06:27Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-bf212a89d20e468b8a5eed05f8efa9ca2022-12-22T04:22:46ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2022-12-01910.3389/fmolb.2022.10917571091757PDX1 is the cornerstone of pancreatic β-cell functions and identityNour Ebrahim0Nour Ebrahim1Ksenia Shakirova2Erdem Dashinimaev3Erdem Dashinimaev4Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, Moscow, RussiaMoscow Institute of Physics and Technology (State University), Dolgoprudny, RussiaCenter for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, Moscow, RussiaCenter for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, Moscow, RussiaMoscow Institute of Physics and Technology (State University), Dolgoprudny, RussiaDiabetes has been a worldwide healthcare problem for many years. Current methods of treating diabetes are still largely directed at symptoms, aiming to control the manifestations of the pathology. This creates an overall need to find alternative measures that can impact on the causes of the disease, reverse diabetes, or make it more manageable. Understanding the role of key players in the pathogenesis of diabetes and the related β-cell functions is of great importance in combating diabetes. PDX1 is a master regulator in pancreas organogenesis, the maturation and identity preservation of β-cells, and of their role in normal insulin function. Mutations in the PDX1 gene are correlated with many pancreatic dysfunctions, including pancreatic agenesis (homozygous mutation) and MODY4 (heterozygous mutation), while in other types of diabetes, PDX1 expression is reduced. Therefore, alternative approaches to treat diabetes largely depend on knowledge of PDX1 regulation, its interaction with other transcription factors, and its role in obtaining β-cells through differentiation and transdifferentiation protocols. In this article, we review the basic functions of PDX1 and its regulation by genetic and epigenetic factors. Lastly, we summarize different variations of the differentiation protocols used to obtain β-cells from alternative cell sources, using PDX1 alone or in combination with various transcription factors and modified culture conditions. This review shows the unique position of PDX1 as a potential target in the genetic and cellular treatment of diabetes.https://www.frontiersin.org/articles/10.3389/fmolb.2022.1091757/fullPDX1pancreasβ-cellsinsulindiabetes |
| spellingShingle | Nour Ebrahim Nour Ebrahim Ksenia Shakirova Erdem Dashinimaev Erdem Dashinimaev PDX1 is the cornerstone of pancreatic β-cell functions and identity Frontiers in Molecular Biosciences PDX1 pancreas β-cells insulin diabetes |
| title | PDX1 is the cornerstone of pancreatic β-cell functions and identity |
| title_full | PDX1 is the cornerstone of pancreatic β-cell functions and identity |
| title_fullStr | PDX1 is the cornerstone of pancreatic β-cell functions and identity |
| title_full_unstemmed | PDX1 is the cornerstone of pancreatic β-cell functions and identity |
| title_short | PDX1 is the cornerstone of pancreatic β-cell functions and identity |
| title_sort | pdx1 is the cornerstone of pancreatic β cell functions and identity |
| topic | PDX1 pancreas β-cells insulin diabetes |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2022.1091757/full |
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