The abstract is read at the publisher; the summary is JClub's.
STING-seq linked 76 cis-regulatory elements to 75 target genes at bone mineral density GWAS loci in human fetal osteoblasts, including a CXCL12 enhancer over 500 kb away.
- Why it matters: Most BMD GWAS signals are noncoding, leaving causal genes and mechanisms unclear; connecting CREs to target genes is needed to interpret genetic risk for osteoporosis.
- What they did: The framework combined biobank-scale GWAS with single-cell CRISPRi screening across osteogenic differentiation in hFOB cells, then validated key CRE–gene links using arrayed CRISPRi and activation.
- The result: CRISPRi regulatory effects were broadly reproduced in primary human mesenchymal stem cells (82% concordant; Pearson r = 0.83), and trans-regulatory networks plus the DAP3–YY1AP1 bidirectional promoter implicated DAP3 in mineralization via mitochondrial pathways.
The findingWhy it mattersWhat they didThe result
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