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Bioinformatics and single-cell CRISPRi-based screen reveals effector genes and implicates multi-tissue etiology for BMD

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE261284 | GEO | 2024/04/17

REPOSITORIES: GEO

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Bioinformatics and single-cell CRISPRi-based screen reveals effector genes and implicates multi-tissue etiology for BMD [scCRISPR screen]

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Bioinformatics and single-cell CRISPRi-based screen reveals effector genes and implicates multi-tissue etiology for BMD

Project description:Bioinformatics and single-cell CRISPRi-based screen reveals effector genes and implicates multi-tissue etiology for BMD

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Bioinformatics and single-cell CRISPRi-based screen reveals effector genes and implicates multi-tissue etiology for BMD [scCRISPR screen]

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Bioinformatics and single-cell CRISPRi-based screen reveals effector genes and implicates multi-tissue etiology for BMD [ATAC-seq]

Project description:Bioinformatics and single-cell CRISPRi-based screen reveals effector genes and implicates multi-tissue etiology for BMD [ATAC-seq]

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Bioinformatics and single-cell CRISPRi-based screen reveals effector genes and implicates multi-tissue etiology for BMD [Capture-C]

Project description:Bioinformatics and single-cell CRISPRi-based screen reveals effector genes and implicates multi-tissue etiology for BMD [Capture-C]

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Bioinformatics and single-cell CRISPRi-based screen reveals effector genes and implicates multi-tissue etiology for BMD [bulk RNA-seq]

Project description:Bioinformatics and single-cell CRISPRi-based screen reveals effector genes and implicates multi-tissue etiology for BMD [bulk RNA-seq]

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GWAS-informed data integration and non-coding CRISPRi screen illuminate genetic etiology of bone mineral density.

Project description:Over 1,100 independent signals have been identified with genome-wide association studies (GWAS) for bone mineral density (BMD), a key risk factor for mortality-increasing fragility fractures; however, the effector gene(s) for most remain unknown. Informed by a variant-to-gene mapping strategy implicating 89 non-coding elements predicted to regulate osteoblast gene expression at BMD GWAS loci, we executed a single-cell CRISPRi screen in human fetal osteoblast 1.19 cells (hFOBs). The BMD relevance of hFOBs was supported by heritability enrichment from cross-cell type stratified LD-score regression involving 98 cell types grouped into 15 tissues. 24 genes showed perturbation in the screen, with four (ARID5B, CC2D1B, EIF4G2, and NCOA3) exhibiting consistent effects upon siRNA knockdown on three measures of osteoblast maturation and mineralization. Lastly, additional heritability enrichments, genetic correlations, and multi-trait fine-mapping revealed that many BMD GWAS signals are pleiotropic and likely mediate their effects via non-bone tissues that warrant attention in future screens.

| S-EPMC10983984 | biostudies-literature

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