title: Transdifferentiation of pancreatic α-cells into insulin-secreting cells: From experimental models to underlying mechanisms.
abstract: Pancreatic insulin-secreting β-cells are essential regulators of glucose metabolism. New strategies are currently being investigated to create insulin-producing β cells to replace deficient β cells, including the differentiation of either stem or progenitor cells, and the newly uncovered transdifferentiation of mature non-β islet cell types. However, in order to correctly drive any cell to adopt a new β-cell fate, a better understanding of the in vivo mechanisms involved in the plasticity and biology of islet cells is urgently required. Here, we review the recent studies reporting the phenomenon of transdifferentiation of α cells into β cells by focusing on the major candidates and contexts revealed to be involved in adult β-cell regeneration through this process. The possible underlying mechanisms of transdifferentiation and the interactions between several key factors involved in the process are also addressed. We propose that it is of importance to further study the molecular and cellular mechanisms underlying α- to β-cell transdifferentiation, in order to make β-cell regeneration from α cells a relevant and realizable strategy for developing cell-replacement therapy.
authors.affiliation: Jieli Lu, Chang-Xian Zhang, Sino-French Life Science and Genomic Center, the E-Institute of Shanghai, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai 200025, China.
authors.forename: Jieli
authors.initials: J
authors.lastname: Lu
authors.affiliation: Jieli Lu, Chang-Xian Zhang, Sino-French Life Science and Genomic Center, the E-Institute of Shanghai, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai 200025, China.
authors.forename: Rami
authors.initials: R
authors.lastname: Jaafer
authors.affiliation: Jieli Lu, Chang-Xian Zhang, Sino-French Life Science and Genomic Center, the E-Institute of Shanghai, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai 200025, China.
authors.forename: Rémy
authors.initials: R
authors.lastname: Bonnavion
authors.affiliation: Jieli Lu, Chang-Xian Zhang, Sino-French Life Science and Genomic Center, the E-Institute of Shanghai, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai 200025, China.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bertolino
authors.affiliation: Jieli Lu, Chang-Xian Zhang, Sino-French Life Science and Genomic Center, the E-Institute of Shanghai, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai 200025, China.
authors.forename: Chang-Xian
authors.initials: CX
authors.lastname: Zhang
keywords: Cell-replacement therapy; Diabetes mellitus; Transdifferentiation; α-cell; β-cell