Circadian Rhythms of Clock Genes After Transplantation of Mesenchymal Stem Cells with Type 2 Diabetes Mellitus

Abstract

Regenerative therapy involving stem cell transplantation has become an option for the radical treatment of diabetes mellitus. Disruption in the clock genes of stem cells affects the homeostasis of transplanted tissues. We examined the circadian rhythm of genes in transplanted adipose-derived mesenchymal stem cells derived from a patient with type 2 diabetes mellitus (T2DM-ADSC). The clock genes (PER2, CLOCK1, CRY1, and ARNTL[BMAL1]) exhibited similar daily fluctuations in phase and amplitude between a group transplanted with adipose-derived mesenchymal stem cells derived from a healthy individual (N-ADSC) and a group transplanted with T2DM-ADSC. The findings demonstrated that clock genes in stem cells are synchronized with those in living organisms. Next-generation sequencing was then employed to categorize genes that exhibited variation in expression between N-ADSC and T2DM-ADSC. MTATP8P1 and NDUFA7_2 gene expression was significantly reduced at two time points (ZT6 and ZT18), and daily fluctuations were lost. The present study reports, for the first time, that the circadian rhythms of MTATP8P1 and NDUFA7_2, genes involved in mitochondrial processes, are altered in T2DM-ADSC.