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Kempf, J.* ; Knelles, K.* ; Hersbach, B.A.* ; Petrik, D. ; Riedemann, T.* ; Bednarova, V.* ; Janjic, A.* ; Simon-Ebert, T.* ; Enard, W.* ; Smialowski, P. ; Götz, M. ; Masserdotti, G.

Heterogeneity of neurons reprogrammed from spinal cord astrocytes by the proneural factors Ascl1 and Neurogenin2.

Cell Rep. 36:109409 (2021)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Astrocytes are a viable source for generating new neurons via direct conversion. However, little is known about the neurogenic cascades triggered in astrocytes from different regions of the CNS. Here, we examine the transcriptome induced by the proneural factors Ascl1 and Neurog2 in spinal cord-derived astrocytes in vitro. Each factor initially elicits different neurogenic programs that later converge to a V2 interneuron-like state. Intriguingly, patch sequencing (patch-seq) shows no overall correlation between functional properties and the transcriptome of the heterogenous induced neurons, except for K-channels. For example, some neurons with fully mature electrophysiological properties still express astrocyte genes, thus calling for careful molecular and functional analysis. Comparing the transcriptomes of spinal cord- and cerebral-cortex-derived astrocytes reveals profound differences, including developmental patterning cues maintained in vitro. These relate to the distinct neuronal identity elicited by Ascl1 and Neurog2 reflecting their developmental functions in subtype specification of the respective CNS region.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Ascl1 ; Neurog2 ; Astrocytes ; Direct Reprogramming ; Patch-seq ; Patterning Genes ; Single-cell Rna-seq ; Spinal Cord; Functional-neurons; Direct Conversion; In-vivo; Parkinsons-disease; Glial-cells; Transcription; Genes; Fibroblasts; Expression; Specification
ISSN (print) / ISBN 2211-1247
e-ISSN 2211-1247
Journal Cell Reports
Quellenangaben Volume: 36, Issue: 3, Pages: , Article Number: 109409 Supplement: ,
Publisher Cell Press
Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Stem Cell Research (ISF)
Grants EU consortium NSC Reconstruct
ERA-Net neuron grant MICRONET
advanced ERC ChroNeuroRepair
German Research Foundation