Time-resolved single-cell screening reveals the dynamic regulatory architecture of human cardiogenesis

Daily single-cell CRISPR screening of 400 CHD-relevant genes in human cardioids over seven developmental days (~975,000 cells) shows perturbation effects depend strongly on developmental stage.

• Why it matters: Existing human fetal heart atlases miss key time points, and prior perturbation screens test only a few stages, leaving unclear when disease genes act during cardiogenesis.
• What they did: The study combined time-resolved single-cell CRISPR screening in cardioids with a matched multiome atlas, sampling daily across seven days and integrating perturbation phenotypes with multiome data.
• The result: Stage-specific regulatory networks were recovered, HOXB2 and HOXB3 were nominated as candidate cardiac regulators, and gene function proved highly context dependent, with some effects persisting after expression declined.

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