PuSH - Publication Server of Helmholtz Zentrum München

Masserdotti, G. ; Gillotin, S.* ; Sutor, B.* ; Drechsel, D.* ; Irmler, M. ; Jørgensen, H.F.* ; Sass, S. ; Theis, F.J. ; Beckers, J. ; Berninger, B.* ; Guillemot, F.* ; Götz, M.

Transcriptional mechanisms of proneural factors and REST in regulating neuronal reprogramming of astrocytes.

Cell Stem Cell 17, 74-88 (2015)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Direct lineage reprogramming induces dramatic shifts in cellular identity, employing poorly understood mechanisms. Recently, we demonstrated that expression of Neurog2 or Ascl1 in postnatal mouse astrocytes generates glutamatergic or GABAergic neurons. Here, we take advantage of this model to study dynamics of neuronal cell fate acquisition at the transcriptional level. We found that Neurog2 and Ascl1 rapidly elicited distinct neurogenic programs with only a small subset of shared target genes. Within this subset, only NeuroD4 could by itself induce neuronal reprogramming in both mouse and human astrocytes, while co-expression with Insm1 was required for glutamatergic maturation. Cultured astrocytes gradually became refractory to reprogramming, in part by the repressor REST preventing Neurog2 from binding to the NeuroD4 promoter. Notably, in astrocytes refractory to Neurog2 activation, the underlying neurogenic program remained amenable to reprogramming by exogenous NeuroD4. Our findings support a model of temporal hierarchy for cell fate change during neuronal reprogramming.
Altmetric
Additional Metrics?
Tags
Icb_rene
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 1934-5909
e-ISSN 1875-9777
Journal Cell Stem Cell
Quellenangaben Volume: 17, Issue: 1, Pages: 74-88 Article Number: , Supplement: ,
Publisher Cell Press
Publishing Place Cambridge, Mass.
Non-patent literature Publications
Reviewing status Peer reviewed