Allaway et al. integrate scRNA-seq and scATAC-seq across MGE/CGE interneuron de…

Allaway et al. integrate scRNA-seq and scATAC-seq across MGE/CGE interneuron development: chromatin remodeling precedes transcriptional commitment, and dynamic enhancer accessibility coordinates with TF cascades to drive subtype divergence including CGE Prox1/Sp8/COUP-TFII programs.

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  "n": null,
  "doi": "10.1038/s41586-021-03933-1",
  "year": "2021",
  "claim": "Allaway et al. integrate scRNA-seq and scATAC-seq across MGE/CGE interneuron development: chromatin remodeling precedes transcriptional commitment, and dynamic enhancer accessibility coordinates with TF cascades to drive subtype divergence including CGE Prox1/Sp8/COUP-TFII programs.",
  "title": "Genetic and epigenetic coordination of cortical interneuron development.",
  "authors": "Allaway KC, et al.",
  "journal": "Nature",
  "cite_key": "Allaway2021",
  "effect_size": null,
  "text_access": "fulltext",
  "_source_cluster": "cluster_14_cge_lineage_context",
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  "claim_source_sentence": "One of the hallmarks of the cerebral cortex is the extreme diversity of interneurons1-3. The two largest subtypes of cortical interneurons, parvalbumin- and somatostatin-positive cells, are morphologically and functionally distinct in adulthood but arise from common lineages within the medial ganglionic eminence4-11. This makes them an attractive model for studying the generation of cell diversity. Here we examine how developmental changes in transcription and chromatin structure enable these cells to acquire distinct identities in the mouse cortex. Generic interneuron features are first detected upon cell cycle exit through the opening of chromatin at distal elements. By constructing cell-type-specific gene regulatory networks, we observed that parvalbumin- and somatostatin-positive cells initiate distinct programs upon settling within the cortex. We used these networks to model the differential transcriptional requirement of a shared regulator, Mef2c, and confirmed the accuracy of our predictions through experimental loss-of-function experiments. We therefore reveal how a common molecular program diverges to enable these neuronal subtypes to acquire highly specialized properties "
}

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One of the hallmarks of the cerebral cortex is the extreme diversity of interneurons1-3. The two largest subtypes of cortical interneurons, parvalbumin- and somatostatin-positive cells, are morphologically and functionally distinct in adulthood but arise from common lineages within the medial ganglionic eminence4-11. This makes them an attractive model for studying the generation of cell diversity. Here we examine h...

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