CRISPRi Screening of Enhancers in Human Primary Astrocytes Identifies Regulatory Circuitry Disrupted in Alzheimer’s Disease
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE252965 | GEO | 2025/09/25
REPOSITORIES: GEO
Similar Datasets
Project description:We used CROP-seq to perform a high-throughput, parallel screen of 979 candidate enhancer perturbations in normal human astrocytes (NHAs), a primary cell-line. We identified the target gene(s) for 145 of these candidates, which were enriched for transcription with eRNA, transcription factor footprinting, and superenhancer annotation. Most regulatory interactions were <50kb, targeting the nearest gene in ~50% of cases, but were not typically captured by eQTL or in silico predictions. These data elucidate the regulatory network of an understudied-but-crucial brain cell-type.
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Project description:We used CROP-seq to perform a high-throughput, parallel screen of 979 candidate enhancer perturbations in normal human astrocytes (NHAs), a primary cell-line. We identified the target gene(s) for 145 of these candidates, which were enriched for transcription with eRNA, transcription factor footprinting, and superenhancer annotation. Most regulatory interactions were <50kb, targeting the nearest gene in ~50% of cases, but were not typically captured by eQTL or in silico predictions. These data elucidate the regulatory network of an understudied-but-crucial brain cell-type.
2025-10-01 | GSE255009 | GEO
Project description:We used CROP-seq to perform a high-throughput, parallel screen of 979 candidate enhancer perturbations in normal human astrocytes (NHAs), a primary cell-line. We identified the target gene(s) for 145 of these candidates, which were enriched for transcription with eRNA, transcription factor footprinting, and superenhancer annotation. Most regulatory interactions were <50kb, targeting the nearest gene in ~50% of cases, but were not typically captured by eQTL or in silico predictions. These data elucidate the regulatory network of an understudied-but-crucial brain cell-type.
2025-09-25 | GSE253099 | GEO
Project description:We used CROP-seq to perform a high-throughput, parallel screen of 979 candidate enhancer perturbations in normal human astrocytes (NHAs), a primary cell-line. We identified the target gene(s) for 145 of these candidates, which were enriched for transcription with eRNA, transcription factor footprinting, and superenhancer annotation. Most regulatory interactions were <50kb, targeting the nearest gene in ~50% of cases, but were not typically captured by eQTL or in silico predictions. These data elucidate the regulatory network of an understudied-but-crucial brain cell-type.
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Project description:Enhancers are transcription factor platforms that also bind RNA polymerase II and generate enhancer RNAs (eRNA). Although eRNAs have been suggested as predictors of enhancer activities and possibly key components facilitating transcription, there is little genetic evidence to support this. We address the biology of eRNAs in vivo and investigate eRNA patterns, expression levels and possible functions within a mammary-specific super-enhancer that is composed of three units with distinct transcriptional capacities. We show that eRNA levels do not correspond with the activities of their respective enhancer units. However, changes in eRNA expression upon deletion of individual enhancer units reflect the change in overall super-enhancer activity. These data provide genetic evidence that eRNA levels are not a reliable readout of individual enhancers, but they predict superenhancer activity in the absence of constituent elements.
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