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Direct Reprogramming of Somatic Cells into Induced β-Cells: An Overview

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Cell Biology and Translational Medicine, Volume 19

Abstract

The persistent shortage of insulin-producing islet mass or β-cells for transplantation in the ever-growing diabetic population worldwide is a matter of concern. To date, permanent cure to this medical complication is not available and soon after the establishment of lineage-specific reprogramming, direct β-cell reprogramming became a viable alternative for β-cell regeneration. Direct reprogramming is a straightforward and powerful technique that can provide an unlimited supply of cells by transdifferentiating terminally differentiated cells toward the desired cell type. This approach has been extensively used by multiple groups to reprogram non-β-cells toward insulin-producing β-cells. The β-cell identity has been achieved by various studies via ectopic expression of one or more pancreatic-specific transcription factors in somatic cells, bypassing the pluripotent state. This work highlights the importance of the direct reprogramming approaches (both integrative and non-integrative) in generating autologous β-cells for various applications. An in-depth understanding of the strategies and cell sources could prove beneficial for the efficient generation of integration-free functional insulin-producing β-cells for diabetic patients lacking endogenous β-cells.

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Abbreviations

Ad:

Adenovirus

ESCs:

Embryonic stem cells

GLP1:

Glucagon-like peptide 1

GLUT2:

Glucose transporter 2

GTPase:

Guanosine triphosphate binding protein

HNF-4α:

Hepatocyte nuclear factor-4 α

IFN-γ:

Interferon-γ

IL-1β:

Interleukin-1β

MAPK:

Mitogen-activated protein kinase

NOD-SCID:

Nonobese diabetic-severe combined immunodeficiency

PI3K:

Phosphoinositide 3-kinase/phosphatidylinositol 3-kinase

PP:

Pancreatic polypeptide

STAT:

Signal transducer and activator of transcription

TGFβ:

Transforming growth factor β

TNFα:

Tumor necrosis factor-α

VP16:

Virus protein 16

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Acknowledgments

We thank all the members of the Laboratory for Stem Cell Engineering and Regenerative Medicine (SCERM) for their critical reading and excellent support. This work was financially supported by the Ministry of Science and Technology, Govt. of India (Ref. No.: BT/COE/34/SP28408/2018) under the North East Center for Biological Sciences and Healthcare Engineering (NECBH) outreach program hosted by Indian Institute of Technology Guwahati (IITG), Guwahati, Assam sponsored by Department of Biotechnology (DBT), Govt. of India (NECBH/2019-20/136). This work was partially funded by IIT Guwahati Institutional Top-Up on Start-Up Grant.

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Correspondence to Rajkumar P. Thummer .

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The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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GN was responsible for conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing, and final approval of the manuscript; RKR was responsible for conception and design, collection and/or assembly of data, and final approval of the manuscript; RPT was responsible for conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing, final editing and approval of the manuscript and financial support. All the authors gave consent for publication.

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Narayan, G., Ronima K R, Thummer, R.P. (2022). Direct Reprogramming of Somatic Cells into Induced β-Cells: An Overview. In: Turksen, K. (eds) Cell Biology and Translational Medicine, Volume 19. Advances in Experimental Medicine and Biology(), vol 1410. Springer, Cham. https://doi.org/10.1007/5584_2022_756

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