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)
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
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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
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Language
english
Publication Year
2021
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2021
ISSN (print) / ISBN
2211-1247
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2211-1247
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Volume: 36,
Issue: 3,
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Article Number: 109409
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Cell Press
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50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
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Peer reviewed
POF-Topic(s)
30204 - Cell Programming and Repair
Research field(s)
Stem Cell and Neuroscience
PSP Element(s)
G-500800-001
Grants
EU consortium NSC Reconstruct
ERA-Net neuron grant MICRONET
advanced ERC ChroNeuroRepair
German Research Foundation
Copyright
Erfassungsdatum
2021-08-04