0      0

eSymposia | Tissue Plasticity: Preservation and Alteration of Cellular Identity


Vascular smooth muscle-derived adipocyte progenitors are the cellular origin of cold-induced brown adipocytes


Oct 5, 2020 12:00am ‐ Oct 5, 2020 12:00am

Description

Vascular smooth muscle-derived adipocyte progenitors are the cellular origin of cold-induced brown adipocytes The adipose tissue plays a central role in the regulation of energy homeostasis and is therefore a major contributor to the pathophysiology of obesity and metabolic diseases. Brown adipose tissue is specialized in thermogenic energy expenditure and is an attractive target for anti-obesity therapies. Prolonged cold exposure increases BAT mass and activity partially through de novo recruitment of brown adipocytes as well as the coordinated expansion of other cells within the adipose niche to enable maximal thermogenic activity. However, the source of cold-induced brown adipogenesis and the molecular mechanism regulating BAT expansion is not known. To delineate the cellular remodeling of the thermogenic niche and identify the cellular origin of brown adipocytes, we used single-cell RNA sequencing. We identified a previously unknown population of adipocyte progenitors derived from the vascular smooth muscle lineage (VSM-APC) as the source of brown adipocytes recruited in cold. VSM-APCs specifically express the temperature-sensitive ion channel transient receptor potential cation channel subfamily V member 1 (Trpv1) in brown and white adipose tissue. Lineage tracing studies using the Trpv1Cre Rosa26mTmG mouse model confirmed that the Trpv1pos VSM-APCs are a distinct population of adipocyte progenitors that contribute to brown and white adipocyte pools in vivo and in vitro. Intriguingly, cold exposure promotes the proliferation and differentiation of Trpv1pos progenitors into highly thermogenic brown adipocytes. Together, this work illustrated the landscape of the thermogenic adipose niche remodeling at the single cell resolution and established a new cellular origin of thermogenic adipocytes. This new model for the development of BAT could be critical in designing strategies to increase the number of brown adipocytes in humans. Farnaz Shamsi1,5, Matthew D. Lynes1,5, Mary Piper2, Li-Lun Ho3, Tian Lian Huang1, Yu-Hua Tseng1,4 1 Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA 2 Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA 3 Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA 4 Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA 5 Equal Contributions

Speaker(s):

You must be logged in and own this session in order to post comments.

Print Certificate
Completed on: token-completed_on
Print Transcript
Please select the appropriate credit type:
/
test_id: 
credits: 
completed on: 
rendered in: 
* - Indicates answer is required.
token-content

token-speaker-name
token-index
token-content
token-index
token-content
token-index
token-content
token-index
token-content
token-index
token-content
token-index
token-content
/
/
token-index
token-content
token-index
token-content