NKX6.1 transcription factor: a crucial regulator of pancreatic ? cell development, identity, and proliferation.

ABSTRACT: Understanding the biology underlying the mechanisms and pathways regulating pancreatic ? cell development is necessary to understand the pathology of diabetes mellitus (DM), which is characterized by the progressive reduction in insulin-producing ? cell mass. Pluripotent stem cells (PSCs) can potentially offer an unlimited supply of functional ? cells for cellular therapy and disease modeling of DM. Homeobox protein NKX6.1 is a transcription factor (TF) that plays a critical role in pancreatic ? cell function and proliferation. In human pancreatic islet, NKX6.1 expression is exclusive to ? cells and is undetectable in other islet cells. Several reports showed that activation of NKX6.1 in PSC-derived pancreatic progenitors (MPCs), expressing PDX1 (PDX1+/NKX6.1+), warrants their future commitment to monohormonal ? cells. However, further differentiation of MPCs lacking NKX6.1 expression (PDX1+/NKX6.1-) results in an undesirable generation of non-functional polyhormonal ? cells. The importance of NKX6.1 as a crucial regulator in MPC specification into functional ? cells directs attentions to further investigating its mechanism and enhancing NKX6.1 expression as a means to increase ? cell function and mass. Here, we shed light on the role of NKX6.1 during pancreatic ? cell development and in directing the MPCs to functional monohormonal lineage. Furthermore, we address the transcriptional mechanisms and targets of NKX6.1 as well as its association with diabetes.

SUBMITTER: Aigha II 

PROVIDER: S-EPMC7597038 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature