PDX1, Neurogenin-3, and MAFA: critical transcription regulators for beta cell development and regeneration
Abstract Transcription factors regulate gene expression through binding to specific enhancer sequences. Pancreas/duodenum homeobox protein 1 (PDX1), Neurogenin-3 (NEUROG3), and V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MAFA) are transcription factors critical for beta cell developmen...
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doaj-08f868ffc243405bb5e5a05abe56ea4f2020-11-24T23:21:57ZengBMCStem Cell Research & Therapy1757-65122017-11-01811710.1186/s13287-017-0694-zPDX1, Neurogenin-3, and MAFA: critical transcription regulators for beta cell development and regenerationYaxi Zhu0Qian Liu1Zhiguang Zhou2Yasuhiro Ikeda3Department of Molecular Medicine, Mayo Clinic, College of MedicineDepartment of Orthopedics, The Second Xiangya Hospital, Central South UniversityInstitute of Metabolism and Endocrinology, The Second Xiangya Hospital, Key Laboratory of Diabetes Immunology, Ministry of Education, Central South University, National Clinical Research Center for Metabolic DiseasesDepartment of Molecular Medicine, Mayo Clinic, College of MedicineAbstract Transcription factors regulate gene expression through binding to specific enhancer sequences. Pancreas/duodenum homeobox protein 1 (PDX1), Neurogenin-3 (NEUROG3), and V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MAFA) are transcription factors critical for beta cell development and maturation. NEUROG3 is expressed in endocrine progenitor cells and controls islet differentiation and regeneration. PDX1 is essential for the development of pancreatic exocrine and endocrine cells including beta cells. PDX1 also binds to the regulatory elements and increases insulin gene transcription. Likewise, MAFA binds to the enhancer/promoter region of the insulin gene and drives insulin expression in response to glucose. In addition to those natural roles in beta cell development and maturation, ectopic expression of PDX1, NEUROG3, and/or MAFA has been successfully used to reprogram various cell types into insulin-producing cells in vitro and in vivo, such as pancreatic exocrine cells, hepatocytes, and pluripotent stem cells. Here, we review biological properties of PDX1, NEUROG3, and MAFA, and their applications and limitations for beta cell regenerative approaches. The primary source literature for this review was acquired using a PubMed search for articles published between 1990 and 2017. Search terms include diabetes, insulin, trans-differentiation, stem cells, and regenerative medicine.http://link.springer.com/article/10.1186/s13287-017-0694-zDiabetesTrans-differentiationInduced pluripotent stem cellsEmbryonic stem cellsRegenerative medicine |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yaxi Zhu Qian Liu Zhiguang Zhou Yasuhiro Ikeda |
spellingShingle |
Yaxi Zhu Qian Liu Zhiguang Zhou Yasuhiro Ikeda PDX1, Neurogenin-3, and MAFA: critical transcription regulators for beta cell development and regeneration Stem Cell Research & Therapy Diabetes Trans-differentiation Induced pluripotent stem cells Embryonic stem cells Regenerative medicine |
author_facet |
Yaxi Zhu Qian Liu Zhiguang Zhou Yasuhiro Ikeda |
author_sort |
Yaxi Zhu |
title |
PDX1, Neurogenin-3, and MAFA: critical transcription regulators for beta cell development and regeneration |
title_short |
PDX1, Neurogenin-3, and MAFA: critical transcription regulators for beta cell development and regeneration |
title_full |
PDX1, Neurogenin-3, and MAFA: critical transcription regulators for beta cell development and regeneration |
title_fullStr |
PDX1, Neurogenin-3, and MAFA: critical transcription regulators for beta cell development and regeneration |
title_full_unstemmed |
PDX1, Neurogenin-3, and MAFA: critical transcription regulators for beta cell development and regeneration |
title_sort |
pdx1, neurogenin-3, and mafa: critical transcription regulators for beta cell development and regeneration |
publisher |
BMC |
series |
Stem Cell Research & Therapy |
issn |
1757-6512 |
publishDate |
2017-11-01 |
description |
Abstract Transcription factors regulate gene expression through binding to specific enhancer sequences. Pancreas/duodenum homeobox protein 1 (PDX1), Neurogenin-3 (NEUROG3), and V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MAFA) are transcription factors critical for beta cell development and maturation. NEUROG3 is expressed in endocrine progenitor cells and controls islet differentiation and regeneration. PDX1 is essential for the development of pancreatic exocrine and endocrine cells including beta cells. PDX1 also binds to the regulatory elements and increases insulin gene transcription. Likewise, MAFA binds to the enhancer/promoter region of the insulin gene and drives insulin expression in response to glucose. In addition to those natural roles in beta cell development and maturation, ectopic expression of PDX1, NEUROG3, and/or MAFA has been successfully used to reprogram various cell types into insulin-producing cells in vitro and in vivo, such as pancreatic exocrine cells, hepatocytes, and pluripotent stem cells. Here, we review biological properties of PDX1, NEUROG3, and MAFA, and their applications and limitations for beta cell regenerative approaches. The primary source literature for this review was acquired using a PubMed search for articles published between 1990 and 2017. Search terms include diabetes, insulin, trans-differentiation, stem cells, and regenerative medicine. |
topic |
Diabetes Trans-differentiation Induced pluripotent stem cells Embryonic stem cells Regenerative medicine |
url |
http://link.springer.com/article/10.1186/s13287-017-0694-z |
work_keys_str_mv |
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