Unraveling the Developmental Roadmap toward Human Brown Adipose Tissue

Stefania Carobbio, Anne Claire Guenantin, Myriam Bahri, Sonia Rodriguez-Fdez, Floris Honig, Ioannis Kamzolas, Isabella Samuelson, Kathleen Long, Sherine Awad, Dunja Lukovic, Slaven Erceg, Andrew Bassett, Sasha Mendjan, Ludovic Vallier, Barry S. Rosen, Davide Chiarugi, Antonio Vidal-Puig

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)641-655
Number of pages15
JournalStem Cell Reports
Volume16
Issue number3
Early online date18 Feb 2021
DOIs
Publication statusPublished - 9 Mar 2021

Keywords

  • BAT progenitors
  • brown adipose tissue
  • development
  • differentiation
  • human pluripotent stem cells
  • thermogenesis

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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