Tmem30a Plays Critical Roles in Ensuring the Survival of Hematopoietic Cells and Leukemia Cells in Mice.

The fundamental structure of eukaryotic cell plasma membrane is the phospholipid bilayer, which contains four major phospholipids. These phospholipids are asymmetrically distributed between the outer and inner leaflets. P4-ATPase flippase complexes play essential roles in ensuring this asymmetry. We found that conditional deletion of Tmem30a, the β subunit of P4-ATPase flippase complex, caused pancytopenia in mice. Tmem30a deficiency resulted in depletion of lineage-committed blood cells in the peripheral blood, spleen, and bone marrow. Ablation of Tmem30a also caused the depletion of hematopoietic stem cells (HSCs). HSC RNA sequencing results revealed that multiple biological processes and signal pathways were involved in the event, including mammalian target of rapamycin signaling, genes for HSC stemness, and genes responding to interferons. Our results also revealed that targeting Tmem30a signaling had therapeutic utility in BCR/ABL1-induced chronic myeloid leukemia.