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Transient CREB-mediated transcription is key in direct neuronal reprogramming.
Neurogenesis 4:e1285383 (2017)
Combinations of neuronal determinants and/or small-molecules such as Forskolin (Fk) can be used to convert different cell types into neurons. As Fk is known to activate cAMP-dependent pathways including CREB-activity, we aimed here to determine the role of CREB in reprogramming - including its temporal profile. We show that transient expression of the dominant-positive CREB-VP16 followed by its inactivation mediated by the dominant-negative ICER improves neuronal conversion of astrocytes mediated by the neurogenic determinant Ascl1. Contrarily, persistent over-activation by CREB-VP16 or persistent inhibition by ICER interferes with neuronal reprogramming, with the latter enhancing cell death. Taken together our work shows transient CREB activation as a key effector in neuronal reprogramming.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Bcl-2 ; Creb ; Forskolin ; Icer ; Direct Reprogramming ; Immediate Early Genes ; Neurogenesis
ISSN (print) / ISBN
2326-2133
e-ISSN
2326-2133
Zeitschrift
Neurogenesis
Quellenangaben
Band: 4,
Heft: 1,
Artikelnummer: e1285383
Verlag
Routledge, Taylor & Francis Group
Verlagsort
Abingdon, Oxon [u.a.]
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Stem Cell Research (ISF)