Adipose tissue stromal vascular fraction (SVF) is a source of multipotent mesenchymal stem cells that can be isolated from brown and white adipose tissue. While it is accepted that the precursor cells that give rise to mature adipose tissue reside in the SVF, multipotent adipose stem cells capable of self-renewal have not been molecularly defined. Our preliminary data show that mouse telomerase reverse transcriptase expression (mTert) marks a population of brown and white adipose SVF cells expressing putative adipogenic precursor cell surface markers that are capable of self-renewal and adipogenic differentiation in vitro. Further, the mTert cellular lineage is quiescent in brown and white adipose tissue in vivo from 3 weeks of age until 6 months, however high fat diet caused an increase in mTert lineage proliferation in 8-month old animals. Based on these findings, this project is designed to test the novel hypothesis that mTert expressing cells are multipotent adipose stem cells capable of responding to high fat diet and beta-adrenergic stimulation that serve as differentiation cues. There are two specific aims: 1) Functional and molecular characterization of mTert- expressing cells in vitro comparing these putative adipose stem cells to committed progenitor cells;2) Determine the effects of differentiation cues on mTert cell proliferation and differentiation in adipose in vivo compared to committed progenitor cells from PDGFr?-CreERT2 mice. Identifying adipose tissue stem cells and the mechanisms that govern their proliferation and differentiation will have important significance in the understanding of adipose tissue development and obesity and this knowledge may be applicable in autologous tissue transplants in human disease or injury.
Obesity, driven by increased adiposity is a major public health concern and telomerase expression has been shown to be marker of tissue resident stem cells in several adult tissues, suggesting it may play a role in adipose tissue stem cell maintenance, proliferation and differentiation. The goal of this research proposal is to characterize brown and white adipose tissue telomerase-expressing cells and determine the inductive cues that govern their function and fate. This will lead to a better understanding of adipose tissue development and homeostasis and could help to identify novel strategies for autologous cell transplantation.
|Lynes, Matthew D; Tseng, Yu-Hua (2014) Unwiring the transcriptional heat circuit. Proc Natl Acad Sci U S A 111:14318-9|