Single Cell Deletion of the Transcription Factors Trps1 and Sox9 in Astrocytes Reveals Novel Functions in the Adult Cerebral Cortex

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 play key roles in brain function but it is still poorly understood how these are orchestrated by pan-astrocyte transcriptions factors (TFs). Here we examined the function of the well-known pan-astrocyte TF Sox9 and the novel astrocyte TF Trps1 (Transcriptional Repressor GATA Binding 1) by Cas9-mediated in vivo deletion using Mokola-pseudotyped lentiviral delivery into the adult cerebral cortex. The consequences of deleting either Sox9 or Trps1 alone or simultaneously were explored at ...

Astrocyte-specific lentiviral constructs carrying gRNAs targeting Sox9, Trps1 and or both were injected in the cerebral cortex of adult transgenic mice expressing Cas9 protein. Transduced cells were retrived from the cortex 7 and 21 days post injection and subjected to SmartSeq2 for single cell sequencing