Genetic and genomic studies have revealed the mechanism of mechanical sensing in bulge HF-SCs through a PIEZO1-Ca2+ influx–transcription factor (TF) cascade and provided a mechanistic insight into how HF-SCs leverage PIEZO1-mediated Ca2+ influx to reinforce their unique mechanical microenvironment and maintain SC cell states. The gene discussed is TF; the disease is hydrops fetalis.