Ferroptosis of selective progenitor cell types during embryogenesis ensures proper organ morphogenesis

Ferroptosis occurs in the embryonic lung and kidney during mid- and late-gestation, and Gpx4 dosage in key progenitors is linked to cystic lungs and kidneys.

• Why it matters: The contribution of ferroptosis to embryonic development is unknown, despite apoptosis being known to shape organ formation.
• What they did: The study mapped ferroptosis in embryonic lung and kidney using lipidomic profiling and ferroptosis readouts (TfR1, 4-HNE, TUNEL, mitochondrial defects, membrane breakage, dead remnants) plus single-cell RNA-seq of a ferroptosis gene signature.
• The result: Genetic manipulation of Gpx4—knockout, transgenic overexpression, or conditional deletion—altered lung and kidney morphogenesis, producing cystic lungs and kidneys, hypoplasia of lung epithelia and renal glomeruli, or atelectasis with collapsed alveoli and hypertrophic glomeruli.

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