Phospholipase C delta 4 (PLCδ4) is a nuclear protein involved in cell proliferation and senescence in mesenchymal stromal stem cells

Ca²⁺ is an important second messenger, and it is involved in many cellular processes such as cell death and proliferation. The rise in intracellular Ca²⁺ levels can be due to the generation of inositol 1,4,5-trisphosphate (InsP₃), which is a product of phosphatidylinositol 4,5-bisphosphate (PIP₂) hydrolysis by phospholipases C (PLCs), that leads to Ca²⁺ release from endoplasmic reticulum by InsP₃ receptors (InsP₃R). Ca²⁺ signaling patterns can vary in different regions of the cell and increases in nuclear Ca²⁺ levels have specific biological effects that differ from those of Ca²⁺ increase in the cytoplasm. There are PLCs in the cytoplasm and nucleus, but little is known about the functions of nuclear PLCs. This work aimed to characterize phenotypically the human PLCδ4 (hPLCδ4) in mesenchymal stem cells. This nuclear isoform of PLC is present in different cell types and has a possible role in proliferative processes. In this work, hPLCδ4 was found to be mainly nuclear in human adipose-derived mesenchymal stem cells (hASC). PLCδ4 knockdown demonstrated that it is essential for hASC proliferation, without inducing cell death. An increase of cells in G1, and a reduction of cells on interphase and G2/M in knockdown cells were seen. Furthermore, PLCδ4 knockdown increased the percentage of senescent cells, p16^INK4A+ and p21^Cip1 mRNAs expression, which could explain the impaired cell proliferation. The results show that hPLCδ4 is in involved in cellular proliferation and senescence in hASC.