Heterogeneity of neurons reprogrammed from spinal cord astrocytes by the proneural factors Ascl1 and Neurogenin2
| العنوان: | Heterogeneity of neurons reprogrammed from spinal cord astrocytes by the proneural factors Ascl1 and Neurogenin2 |
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| المؤلفون: | Magdalena Götz, V. Bednarova, J. Kempf, Therese Riedemann, David Petrik, B.A. Hersbach, Tatiana Simon-Ebert, Giacomo Masserdotti, Pawel Smialowski, Wolfgang Enard, Aleksandar Janjic, K. Knelles |
| المصدر: | Cell Reports Cell Rep. 36:109409 (2021) |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Transcription, Genetic, Nerve Tissue Proteins, Neurog2, Biology, Article, General Biochemistry, Genetics and Molecular Biology, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, medicine, Basic Helix-Loop-Helix Transcription Factors, Animals, Ascl1, Gene, 030304 developmental biology, Neurons, 0303 health sciences, single-cell RNA-seq, Correction, patterning genes, Spinal cord, Cellular Reprogramming, direct reprogramming, Electrophysiological Phenomena, Mice, Inbred C57BL, ASCL1, Electrophysiology, medicine.anatomical_structure, Spinal Cord, Organ Specificity, Astrocytes, patch-seq, Direct Reprogramming, Patch-seq, Patterning Genes, Single-cell Rna-seq, Neuroscience, Biomarkers, 030217 neurology & neurosurgery, Astrocyte |
| الوصف: | Summary 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. Graphical abstract Highlights • Ascl1 and Neurog2 induce initially distinct transcriptomes in spinal cord astrocytes • Neurons induced by Ascl1 or Neurog2 converge to a V2 interneuron-like state • Patch-seq shows functional and transcriptional heterogeneity with low correlation • Developmentally established patterning genes are maintained in astrocytes in vitro Kempf et al. show that Ascl1 and Neurog2 elicit initially divergent transcriptional programs in spinal cord astrocytes converging later to a V2 interneuron-like state, according to their developmental role and patterning cues in astrocytes. Patch-seq analysis reveals the heterogeneity of fate conversion with little correlation between transcriptome and electrophysiological properties. |
| وصف الملف: | application/pdf |
| تدمد: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2021.109409 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c75eaa790a0fb81f0229bf1a39202cd7Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c75eaa790a0fb81f0229bf1a39202cd7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22111247 |
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| DOI: | 10.1016/j.celrep.2021.109409 |