Preprint Review Version 2 Preserved in Portico This version is not peer-reviewed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

Keywords

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

Subject

LIFE SCIENCES, Cell & Developmental Biology

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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