Single cell RNA-seq analysis of reprogrammed neurons [Patch-seq2]

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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 ...

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 ...

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 ...