Preprint Review Version 2 Preserved in Portico This version is not peer-reviewed

NKX6.1 Transcription Factor: A Crucial Regulator of Pancreatic β-Cell Development, Identity, and Proliferation

Version 1 : Received: 17 June 2020 / Approved: 21 June 2020 / Online: 21 June 2020 (14:55:19 CEST)
Version 2 : Received: 18 October 2020 / Approved: 19 October 2020 / Online: 19 October 2020 (16:04:27 CEST)

How to cite: Aigha, I.; Abdelalim, E. NKX6.1 Transcription Factor: A Crucial Regulator of Pancreatic β-Cell Development, Identity, and Proliferation. Preprints 2020, 2020060277 (doi: 10.20944/preprints202006.0277.v2). Aigha, I.; Abdelalim, E. NKX6.1 Transcription Factor: A Crucial Regulator of Pancreatic β-Cell Development, Identity, and Proliferation. Preprints 2020, 2020060277 (doi: 10.20944/preprints202006.0277.v2).

Abstract

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 toβ-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 mean 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.

Subject Areas

Diabetes; transcription factor; β-cell mass; pluripotent stem cells; pancreatic progenitors; cell therapy

Comments (1)

Comment 1
Received: 19 October 2020
Commenter: Essam Abdelalim
Commenter's Conflict of Interests: Author
Comment: We added new Figures (Figures 3 & 5) and deleted Figure 4. In addtion, we mdofied the text based on the reviewer's comments. The new version has been accepted for publication in "Stem Cell Reseaerch & Therapy" journal.
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