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2015 ; 4
(11
): 1251-7
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gab.com Text
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English Wikipedia
Concise Review: Reprogramming, Behind the Scenes: Noncanonical Neural Stem Cell
Signaling Pathways Reveal New, Unseen Regulators of Tissue Plasticity With
Therapeutic Implications
#MMPMID26371344
Poser SW
; Chenoweth JG
; Colantuoni C
; Masjkur J
; Chrousos G
; Bornstein SR
; McKay RD
; Androutsellis-Theotokis A
Stem Cells Transl Med
2015[Nov]; 4
(11
): 1251-7
PMID26371344
show ga
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 ?-like cells). Specifically for
acinar-to-?-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. SIGNIFICANCE: Reprogramming is a powerful approach to
change cell identity, with implications in both basic and applied biology. Most
efforts involve the forced expression of key transcription factors, but recently,
success has been reported with manipulating signal transduction pathways that
might intercept them. It is important to start connecting the function of the
classic reprogramming genes to signaling pathways that also mediate
reprogramming, unifying the sciences of signal transduction, stem cell biology,
and epigenetics. Neural stem cell studies have revealed the operation of
noncanonical signaling pathways that are now appreciated to also operate during
reprogramming, offering new mechanistic explanations.