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Mammalian adipogenesis regulator (Areg) cells use retinoic acid signalling to be non- and anti-adipogenic in age-dependent manner

Zachara, Magda; Rainer, Pernille Y; Hashimi, Horia; Russeil, Julie M; Alpern, Daniel; Ferrero, Radiana; Litovchenko, Maria; (2022) Mammalian adipogenesis regulator (Areg) cells use retinoic acid signalling to be non- and anti-adipogenic in age-dependent manner. The EMBO Journal , Article e108206. 10.15252/embj.2021108206. (In press). Green open access

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Abstract

Adipose stem and precursor cells (ASPCs) give rise to adipocytes and determine the composition and plasticity of adipose tissue. Recently, several studies have demonstrated that ASPCs partition into at least three distinct cell subpopulations, including the enigmatic CD142+ cells. An outstanding challenge is to functionally characterise this population, as discrepant properties, from adipogenic to non- and anti-adipogenic, have been reported for these cells. To resolve these phenotypic ambiguities, we characterised mammalian subcutaneous CD142+ ASPCs across various experimental conditions, demonstrating that CD142+ ASPCs exhibit high molecular and phenotypic robustness. Specifically, we find these cells to be firmly non- and anti-adipogenic both in vitro and in vivo, with their inhibitory signals also impacting adipogenic human cells. However, these CD142+ ASPC-specific properties exhibit surprising temporal phenotypic alterations, and emerge only in an age-dependent manner. Finally, using multi-omic and functional assays, we show that the inhibitory nature of these adipogenesis-regulatory CD142+ ASPCs (Aregs) is driven by specifically expressed secretory factors that cooperate with the retinoic acid signalling pathway to transform the adipogenic state of CD142- ASPCs into a non-adipogenic, Areg-like state.

Type: Article
Title: Mammalian adipogenesis regulator (Areg) cells use retinoic acid signalling to be non- and anti-adipogenic in age-dependent manner
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.15252/embj.2021108206
Publisher version: https://doi.org/10.15252/embj.2021108206
Language: English
Additional information: Copyright © 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Keywords: CD142, adipogenesis regulators (Aregs), adipose stem and precursor cells, differentiation, retinoic acid
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
URI: https://discovery.ucl.ac.uk/id/eprint/10154771
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