Adipocytes signal to recruit specific mRNAs from surrounding cells to restore expression deficits [scRNA-Seq]

A major pathway of EV production is potentiated by neutral sphingomyelinase 2 (SMPD3/nSMAse2), an enzyme that generates ceramide from sphingomyelin. In our attempt to study this pathway in adipocytes of male mice, we discovered that the elimination of SMPD3 from adipocytes in vivo triggers a signal to surrounding immune cell-like preadipocytes to release EVs that carry SMPD3 mRNA.

This results in a widespread increase in SMPD3 mRNA in purified null adipocytes without a change in the transcripts of other enzymes involved in ceramide metabolism. These results point to a fundamental, novel, and selective mechanism by which specific mRNA molecules are acquired from the microenvironment to a level that can restore expression of mRNA and protein in a cell that is depleted of the corresponding genetic information.