CRISPRi screens in human iPSC-derived astrocytes elucidate regulators of distinct inflammatory reactive states.

ABSTRACT: Astrocytes become reactive in response to insults to the central nervous system by adopting context-specific cellular signatures and outputs, but a systematic understanding of the underlying molecular mechanisms is lacking. In this study, we developed CRISPR interference screening in human induced pluripotent stem cell-derived astrocytes coupled to single-cell transcriptomics to systematically interrogate cytokine-induced inflammatory astrocyte reactivity. We found that autocrine-paracrine IL-6 and interferon signaling downstream of canonical NF-κB activation drove two distinct inflammatory reactive signatures, one promoted by STAT3 and the other inhibited by STAT3. These signatures overlapped with those observed in other experimental contexts, including mouse models, and their markers wer

SUBMITTER: Leng K 

PROVIDER: S-EPMC9633461 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature