Concise review: Reprogramming, behind the scenes: noncanonical neural stem cell signaling pathways reveal new, unseen regulators of tissue plasticity with therapeutic implications

Poser, Steven W. and Chenoweth, Josh G. and Colantuoni, Carlo and Masjkur, Jimmy and Chrousos, George and Bornstein, Stefan R. and McKay, Ronald D. and Androutsellis-Theotokis, Andreas (2015) Concise review: Reprogramming, behind the scenes: noncanonical neural stem cell signaling pathways reveal new, unseen regulators of tissue plasticity with therapeutic implications. STEM CELLS, 4 (11). pp. 1251-1257. ISSN 1549-4918

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Abstract

Interest is great in the new molecular concepts that explain, at the level of signal transduction, the process of reprogramming. Usually, transcription factors with developmental importance are used, but these approaches give limited information on the signaling networks involved, which could reveal new therapeutic opportunities. Recent findings involving reprogramming by genetic means and soluble factors with well-studied downstream signaling mechanisms, including signal transducer and activator of transcription 3 (STAT3) and hairy and enhancer of split 3 (Hes3), shed new light into the molecular mechanisms that might be involved. We examine the appropriateness of common culture systems and their ability to reveal unusual (noncanonical) signal transduction pathways that actually operate in vivo. We then discuss such novel pathways and their importance in various plastic cell types, culminating in their emerging roles in reprogramming mechanisms. We also discuss a number of reprogramming paradigms (mouse induced pluripotent stem cells, direct conversion to neural stem cells, and in vivo conversion of acinar cells to b-like cells). Specifically for acinar-to-b-cell reprogramming paradigms, we discuss the common view of the underlying mechanism (involving the Janus kinase-STAT pathway that leads to STAT3-tyrosine phosphorylation) and present alternative interpretations that implicate STAT3-serine phosphorylation alone or serine and tyrosine phosphorylation occurring in sequential order. The implications for drug design and therapy are important given that different phosphorylation sites on STAT3 intercept different signaling pathways. We introduce a new molecular perspective in the field of reprogramming with broad implications in basic, biotechnological, and translational research.

Item Type: Article
Keywords: Cellular reprogramming; Cellular transdifferentiation; Induced pluripotent stem cells; Signal transduction; STAT3 transcription factor; Hes3 protein; Pancreatic islets
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Cancer and Stem Cells
Identification Number: 10.5966/sctm.2015-0105
Depositing User: Eprints, Support
Date Deposited: 12 May 2017 14:03
Last Modified: 13 Oct 2017 00:40
URI: http://eprints.nottingham.ac.uk/id/eprint/42834

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