1207-P: Tracing Telomerase Reverse Transcriptase (Tert) Expression to a Dormant Preadipogenic Origin

Abstract

Adipocytes are the major cell type in adipose tissue responsible for maintaining whole body energy homeostasis, and they are continuously replaced via expansion and differentiation of undifferentiated preadipocyte cells that reside within the local niche. In these preadipocytes, the maintenance of telomere length by mouse telomerase reverse transcriptase (mTert) is critical to their function, and premature telomere shortening is associated with metabolic syndrome and insulin resistance, however the specific cell type that expresses mTert in the preadipocyte niche is unknown. In this study, we took a lineage tracing approach to follow the developmental contribution of cells that express the putative stem cell marker mTert to several tissues, including cells residing in adipose tissue stromal vasculature. Using bioluminescent imaging, we were able to localize cells belonging to the mTert lineage in 3 dimensions in live animals. By tracing the fate of cells that express mTert for up to 2 years across the life of individual animals, we identify all tissues that arise from these putative stem cells. Subcutaneous white adipose tissue, which is prone to hyperplasia, showed contribution from the mTert lineage that was increased by high fat diet feeding. Cells that express mTert isolated from adipose tissue expressed preadipocyte markers and they made up less than 2% of the total progenitor pool. The mTert-positive cells possessed the capacity to self-renewal and differentiate into adipocytes, however they required cell-cell contact with mTert-negative cells to proliferate. These data identify a new population of preadipocytes that may contribute to the depot-specific response to HFD. Since individual adipose depots have profoundly different endocrine and metabolic roles, the identification of progenitor cells with depot specific differentiation capacity may provide clues to the mechanisms that govern in whole body physiology. Disclosure M. Lynes: None. D. L. Carlone: None. K. L. Townsend: Other Relationship; Self; Neuright, Inc. D. Breault: None. Y. Tseng: Consultant; Self; Cellarity. Funding National Institutes of Health (T32DK007260, F32DK102320)