Repository logo
 

Unraveling the Developmental Roadmap toward Human Brown Adipose Tissue.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Carobbio, Stefania 
Guenantin, Anne-Claire 
Bahri, Myriam 
Rodriguez-Fdez, Sonia 
Honig, Floris 

Abstract

Increasing brown adipose tissue (BAT) mass and activation is a therapeutic strategy to treat obesity and complications. Obese and diabetic patients possess low amounts of BAT, so an efficient way to expand their mass is necessary. There is limited knowledge about how human BAT develops, differentiates, and is optimally activated. Accessing human BAT is challenging, given its low volume and anatomical dispersion. These constraints make detailed BAT-related developmental and functional mechanistic studies in humans virtually impossible. We have developed and characterized functionally and molecularly a new chemically defined protocol for the differentiation of human pluripotent stem cells (hPSCs) into brown adipocytes (BAs) that overcomes current limitations. This protocol recapitulates step by step the physiological developmental path of human BAT. The BAs obtained express BA and thermogenic markers, are insulin sensitive, and responsive to β-adrenergic stimuli. This new protocol is scalable, enabling the study of human BAs at early stages of development.

Description

Keywords

BAT progenitors, brown adipose tissue, development, differentiation, human pluripotent stem cells, thermogenesis, Adipocytes, Brown, Adipogenesis, Adipose Tissue, Brown, Biomarkers, Cell Culture Techniques, Cell Differentiation, Cell Line, Gene Expression Regulation, Developmental, Humans, Pluripotent Stem Cells, Reproducibility of Results, Thermogenesis, Transcription Factors

Journal Title

Stem Cell Reports

Conference Name

Journal ISSN

2213-6711
2213-6711

Volume Title

16

Publisher

Elsevier BV
Sponsorship
European Research Council (669879)
European Research Council (741707)
Wellcome Trust (203151/Z/16/Z)
Medical Research Council (G0701448)
National Centre for the Replacement Refinement and Reduction of Animals in Research (NC/N001540/1)
Engineering and Physical Sciences Research Council (TS/H001220/1)
Medical Research Council (1948243)
Medical Research Council (MC_PC_17230)
British Heart Foundation (RG/18/7/33636)
MRC (MC_UU_00014/2)
ERC