Unraveling the Developmental Roadmap toward Human Brown Adipose Tissue

Stem Cell Reports. 2021 Mar 9;16(3):641-655. doi: 10.1016/j.stemcr.2021.01.013. Epub 2021 Feb 18.

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.

Keywords: BAT progenitors; brown adipose tissue; development; differentiation; human pluripotent stem cells; thermogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes, Brown / metabolism*
  • Adipogenesis*
  • Adipose Tissue, Brown / metabolism*
  • Biomarkers / metabolism
  • Cell Culture Techniques / methods*
  • Cell Differentiation
  • Cell Line
  • Gene Expression Regulation, Developmental
  • Humans
  • Pluripotent Stem Cells / metabolism*
  • Reproducibility of Results
  • Thermogenesis*
  • Transcription Factors / metabolism*

Substances

  • Biomarkers
  • Transcription Factors