title: Proper activation of MafA is required for optimal differentiation and maturation of pancreatic β-cells.
abstract: A key therapeutic approach for the treatment of Type 1 diabetes (T1D) is transplantation of functional islet β-cells. Despite recent advances in generating stem cell-derived glucose-responsive insulin(+) cells, their further maturation to fully functional adult β-cells still remains a daunting task. Conquering this hurdle will require a better understanding of the mechanisms driving maturation of embryonic insulin(+) cells into adult β-cells, and the implementation of that knowledge to improve current differentiation protocols. Here, we will review our current understanding of β-cell maturation, and discuss the contribution of key β-cell transcription factor MafA, to this process. The fundamental importance of MafA in regulating adult β-cell maturation and function indicates that enhancing MafA expression may improve the generation of definitive β-cells for transplantation. Additionally, we suggest that the temporal control of MafA induction at a specific stage of β-cell differentiation will be the next critical challenge for achieving optimum maturation of β-cells.
authors.affiliation: Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA. Electronic address: elkhattabilham@gmail.com.
authors.forename: Ilham
authors.initials: I
authors.lastname: El Khattabi
authors.affiliation: Cardiovascular and Metabolic Diseases, MedImmune, Gaithersburg, MD 20878, USA. Electronic address: sharmaar@medimmune.com.
authors.forename: Arun
authors.initials: A
authors.lastname: Sharma
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D051473:Maf Transcription Factors, Large / Q000235:genetics / Q000378:metabolism*
chemical_list: D051473:Maf Transcription Factors, Large
keywords: MafA; insulin transcription factor; stem cell differentiation; β-cell differentiation; β-cell maturation; β-cells