Heterogeneity of neurons reprogrammed from spinal cord astrocytes by the proneural factors Ascl1 and Neurogenin2
Actions 
Order Assays
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.
Export PNG
Download
Creators and Submitter
Views: 25
Created: 6th Aug 2026 at 07:05
TagsThis item has not yet been tagged.
Related items
https://orcid.org/0000-0003-1551-9203
Projects: CRC1002: Modulatory Units in Heart Failure, TRR 274: Checkpoints of Central Nervous System Recovery, SFB 1190: Compartmental Gates and Contact Sites in Cells
Web page: Not specified
https://rdp.sfb274.de/ (Research Data Platform) https://gepris.dfg.de/gepris/projekt/408885537 (DFG Gepris entry) The central nervous system (CNS) is a terminally differentiated tissue, where any insult carries a heightened risk - yet the tissue response to these insults is variable and can range from irreversible destruction to almost complete recovery. The rules that instruct these divergent outcomes are still unknown. The aim of this CRC is therefore to understand the biology of the multicellular ...
Programme: Sonderforschungsbereiche/Collaborative Research Centers
Public web page: https://www.sfb274.de/
Neuronal loss in acute or chronic brain disease could be treated by neuronal replacement strategies, such as transplantation of young neurons, if they integrate properly into the existing networks. Here we explore the cell-based and molecular mechanisms causing hyperinnervation and overshoot loss of input connectivity as well as the newly discovered hurdle in output connectivity, the lack of myelination. Candidate as well as unbiased approaches are pursued to identify the critical checkpoints and ...
Submitter: Camilla Giudici
Studies: Astrocyte heterogeneity reveals region-specific astrogenesis in the whit..., Brain injury environment critically influences the connectivity of trans..., Direct neuronal reprogramming of NDUFS4 patient cells identifies the unf..., Direct neuronal reprogramming of mouse astrocytes is associated with mul..., Heterogeneity of neurons reprogrammed from spinal cord astrocytes by the..., Injury-specific factors in the cerebrospinal fluid regulate astrocyte pl..., Single Cell Deletion of the Transcription Factors Trps1 and Sox9 in Astr...
Assays: Expression profiling, Expression profiling by array, Expression profiling: Bulk RNA-seq (human), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Single-cell multiome (scRNA-seq + scATAC-seq), Bul..., Expression profiling: Spatial Transcriptomics (mouse), Expression profiling: Spatial Transcriptomics (mouse), Expression profiling: scRNA-seq (human) (Day 20), Expression profiling: scRNA-seq (human) (Day 5), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Shotgun proteomics (human), Shotgun proteomics (mouse), scRNA-seq and scATAC-seq
Submitter: Camilla Giudici
Assay type: Transcriptomics
Technology type: Sequencing
Investigation: C05 - Glial checkpoints for neuronal circuitry ...
Submitter: Camilla Giudici
Assay type: Transcriptomics
Technology type: Sequencing
Investigation: C05 - Glial checkpoints for neuronal circuitry ...
MACS-sorted astrocytes, obtained from postnatal mouse spinalc cord, were transduced in vitro with Ascl1 and Neurog2. Reprogrammed cells were analyzed by electrophysiology ar 3-to-4 weeks, and then single cells were collected and subjected to SmartSeq2 amplification
Creators: None
Submitter: Camilla Giudici
MACS-sorted astrocytes, obtained from postnatal mouse spinal cord, were transduced in vitro with Ascl1 and Neurog2. Reprogrammed cells were collected from the coverslips by suction and subjected to SmartSeq2 amplification
Creators: None
Submitter: Camilla Giudici
Purpose of the study is to compare the transcriptional profiles of astrocytes obtained from cortex gray matter and spinal cord of postnatal mice. Astrocytes were isolated from 2 regions via ACSA-2 sorting, cultured for 7 days and then subjected to RNA-seq
Creators: None
Submitter: Camilla Giudici
Spinal cord-derived astrocytes were transduced in cultures with retrovirus enconding a tamoxifen-dependent form of Ascl1 and Neurog2.Cells were treated for 24 hours, then transduced cells were FACS-sorted and their transcriptome analyzed.
Creators: None
Submitter: Camilla Giudici
Abstract
Authors: J. Kempf, K. Knelles, B.A. Hersbach, D. Petrik, T. Riedemann, V. Bednarova, A. Janjic, T. Simon-Ebert, W. Enard, P. Smialowski, M. Götz, G. Masserdotti
Date Published: 1st Jul 2021
Publication Type: Journal Article
