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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.; Chenoweth, Josh G.; Colantuoni, Carlo; Masjkur, Jimmy; Chrousos, George; Bornstein, Stefan R.; McKay, Ronald D.; Androutsellis-Theotokis, Andreas

Authors

Steven W. Poser

Josh G. Chenoweth

Carlo Colantuoni

Jimmy Masjkur

George Chrousos

Stefan R. Bornstein

Ronald D. McKay

Andreas Androutsellis-Theotokis



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.

Citation

Poser, S. W., Chenoweth, J. G., Colantuoni, C., Masjkur, J., Chrousos, G., Bornstein, S. R., …Androutsellis-Theotokis, A. (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), doi:10.5966/sctm.2015-0105

Journal Article Type Article
Acceptance Date Jul 8, 2015
Online Publication Date Sep 14, 2015
Publication Date Nov 1, 2015
Deposit Date May 12, 2017
Journal STEM CELLS
Print ISSN 1066-5099
Electronic ISSN 1549-4918
Publisher AlphaMed Press
Peer Reviewed Peer Reviewed
Volume 4
Issue 11
DOI https://doi.org/10.5966/sctm.2015-0105
Keywords Cellular reprogramming; Cellular transdifferentiation; Induced pluripotent stem cells; Signal transduction; STAT3 transcription factor; Hes3 protein; Pancreatic islets
Public URL http://eprints.nottingham.ac.uk/id/eprint/42834
Publisher URL http://onlinelibrary.wiley.com/doi/10.5966/sctm.2015-0105/full
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf