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

• Published in: Stem cell research & therapy Vol. 11; no. 1; p. 459
• Main Authors: Aigha, Idil I, Abdelalim, Essam M
• Format: Journal Article
• Language: English
• Published: England BioMed Central 29.10.2020; BMC
• Subjects: Beta cells; Cell Differentiation; Cell Proliferation; Cell therapy; Diabetes; Diabetes mellitus; Glucose; Homeobox; Homeodomain Proteins - genetics; Humans; Insulin; Insulin-Secreting Cells; Islet cells; Nkx6.1 protein; Pancreas; Pancreatic progenitors; Pathogenesis; Pluripotency; Pluripotent stem cells; Polypeptides; Review; Stem cells; Trans-Activators - genetics; Transcription factor; Transcription factors; Transplants & implants; β cell mass; Pancreatic progenitors; Cell therapy; Diabetes; Pluripotent stem cells; Transcription factor; β cell mass
• ISSN: 1757-6512; 1757-6512
• DOI: 10.1186/s13287-020-01977-0

Understanding the biology underlying the mechanisms and pathways regulating pancreatic β cell development is necessary to understand the pathology of diabetes mellitus (DM), which is characterized by the progressive reduction in insulin-producing β cell mass. Pluripotent stem cells (PSCs) can potentially offer an unlimited supply of functional β 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 β cell function and proliferation. In human pancreatic islet, NKX6.1 expression is exclusive to β 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 β cells. However, further differentiation of MPCs lacking NKX6.1 expression (PDX1 /NKX6.1 ) results in an undesirable generation of non-functional polyhormonal β cells. The importance of NKX6.1 as a crucial regulator in MPC specification into functional β cells directs attentions to further investigating its mechanism and enhancing NKX6.1 expression as a means to increase β cell function and mass. Here, we shed light on the role of NKX6.1 during pancreatic β 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.