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

doi:10.1016/j.stemcr.2021.01.013

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

Department of Life Sciences

Research output: Contribution to journal › Article › peer-review

9 Citations (SciVal)

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 language	English
Pages (from-to)	641-655
Number of pages	15
Journal	Stem Cell Reports
Volume	16
Issue number	3
Early online date	18 Feb 2021
DOIs	https://doi.org/10.1016/j.stemcr.2021.01.013
Publication status	Published - 9 Mar 2021

Bibliographical note

Funding Information:
We thank the CGaP team at Sanger for their technical assistance, the Molecular Cytogenetics Lab at Sanger for the karyotyping of the cells, and the DNA pipeline at Sanger for running the RNA-seq. The PAZ6 cell line was a kind gift from Dr Tarik Issad, Institute Cochin, Paris, France. We thank Dr Sergio Rodriguez-Cuenca for his scientific and technical advice and Dr Sam Virtue for his technical advice and revision of the manuscript. This work was funded by the ERC Senior Investigator award (669879). L.V.?s lab is funded by the ERC advanced grant New-Chol, the Cambridge University Hospital's National Institute for Health Research Biomedical Research Centre, and a core support grant from the Wellcome and MRC to the Wellcome ? Medical Research Council Cambridge Stem Cell Institute.

Funding Information:
We thank the CGaP team at Sanger for their technical assistance, the Molecular Cytogenetics Lab at Sanger for the karyotyping of the cells, and the DNA pipeline at Sanger for running the RNA-seq. The PAZ6 cell line was a kind gift from Dr Tarik Issad, Institute Cochin, Paris, France. We thank Dr Sergio Rodriguez-Cuenca for his scientific and technical advice and Dr Sam Virtue for his technical advice and revision of the manuscript. This work was funded by the ERC Senior Investigator award (669879). L.V.’s lab is funded by the ERC advanced grant New-Chol, the Cambridge University Hospital’s National Institute for Health Research Biomedical Research Centre , and a core support grant from the Wellcome and MRC to the Wellcome – Medical Research Council Cambridge Stem Cell Institute .

Publisher Copyright:
© 2021 The Authors

Keywords

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

ASJC Scopus subject areas

Biochemistry
Genetics
Developmental Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.stemcr.2021.01.013Licence: CC BY

Cite this

Carobbio, S., Guenantin, A. C., Bahri, M., Rodriguez-Fdez, S., Honig, F., Kamzolas, I., Samuelson, I., Long, K., Awad, S., Lukovic, D., Erceg, S., Bassett, A., Mendjan, S., Vallier, L., Rosen, B. S., Chiarugi, D., & Vidal-Puig, A. (2021). Unraveling the Developmental Roadmap toward Human Brown Adipose Tissue. Stem Cell Reports, 16(3), 641-655. https://doi.org/10.1016/j.stemcr.2021.01.013

Carobbio, S, Guenantin, AC, Bahri, M, Rodriguez-Fdez, S, Honig, F, Kamzolas, I, Samuelson, I, Long, K, Awad, S, Lukovic, D, Erceg, S, Bassett, A, Mendjan, S, Vallier, L, Rosen, BS, Chiarugi, D & Vidal-Puig, A 2021, 'Unraveling the Developmental Roadmap toward Human Brown Adipose Tissue', Stem Cell Reports, vol. 16, no. 3, pp. 641-655. https://doi.org/10.1016/j.stemcr.2021.01.013

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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.",

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

note = "Funding Information: We thank the CGaP team at Sanger for their technical assistance, the Molecular Cytogenetics Lab at Sanger for the karyotyping of the cells, and the DNA pipeline at Sanger for running the RNA-seq. The PAZ6 cell line was a kind gift from Dr Tarik Issad, Institute Cochin, Paris, France. We thank Dr Sergio Rodriguez-Cuenca for his scientific and technical advice and Dr Sam Virtue for his technical advice and revision of the manuscript. This work was funded by the ERC Senior Investigator award (669879). L.V.?s lab is funded by the ERC advanced grant New-Chol, the Cambridge University Hospital's National Institute for Health Research Biomedical Research Centre, and a core support grant from the Wellcome and MRC to the Wellcome ? Medical Research Council Cambridge Stem Cell Institute. Funding Information: We thank the CGaP team at Sanger for their technical assistance, the Molecular Cytogenetics Lab at Sanger for the karyotyping of the cells, and the DNA pipeline at Sanger for running the RNA-seq. The PAZ6 cell line was a kind gift from Dr Tarik Issad, Institute Cochin, Paris, France. We thank Dr Sergio Rodriguez-Cuenca for his scientific and technical advice and Dr Sam Virtue for his technical advice and revision of the manuscript. This work was funded by the ERC Senior Investigator award (669879). L.V.{\textquoteright}s lab is funded by the ERC advanced grant New-Chol, the Cambridge University Hospital{\textquoteright}s National Institute for Health Research Biomedical Research Centre , and a core support grant from the Wellcome and MRC to the Wellcome – Medical Research Council Cambridge Stem Cell Institute . Publisher Copyright: {\textcopyright} 2021 The Authors",

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AU - Honig, Floris

AU - Kamzolas, Ioannis

AU - Samuelson, Isabella

AU - Long, Kathleen

AU - Awad, Sherine

AU - Lukovic, Dunja

AU - Erceg, Slaven

AU - Bassett, Andrew

AU - Mendjan, Sasha

AU - Vallier, Ludovic

AU - Rosen, Barry S.

AU - Chiarugi, Davide

AU - Vidal-Puig, Antonio

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Unraveling the Developmental Roadmap toward Human Brown Adipose Tissue

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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