Multicellular Perturb-seq Reveals Lineage-Specific Transcriptional Control During Human Cardiac Organoid Development

Cardiac organoid development in hiPSCs enables single-cell Perturb-seq to systematically dissect how cardiac and vascular transcription factors coordinate lineage commitment across cardiomyocytes and endothelial cells.

• Why it matters: Heart formation depends on coordinated differentiation of multiple lineages, but how transcription factors synchronize cardiac and vascular programs—especially across stages and in progenitors—remains unclear.
• What they did: The study uses human induced pluripotent stem cell–derived cardiac organoids with simultaneous endothelial and cardiomyocyte differentiation, combined with CRISPRi-based Perturb-seq for high-throughput single-cell TF perturbations.
• The result: This approach provides a framework to resolve TF-driven regulatory programs and cross-lineage signaling during human cardiovascular differentiation at single-cell resolution.

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