eprintid: 10154771 rev_number: 9 eprint_status: archive userid: 699 dir: disk0/10/15/47/71 datestamp: 2022-08-31 14:21:48 lastmod: 2022-08-31 14:22:08 status_changed: 2022-08-31 14:21:48 type: article metadata_visibility: show sword_depositor: 699 creators_name: Zachara, Magda creators_name: Rainer, Pernille Y creators_name: Hashimi, Horia creators_name: Russeil, Julie M creators_name: Alpern, Daniel creators_name: Ferrero, Radiana creators_name: Litovchenko, Maria creators_name: Deplancke, Bart title: Mammalian adipogenesis regulator (Areg) cells use retinoic acid signalling to be non- and anti-adipogenic in age-dependent manner ispublished: inpress divisions: C10 divisions: G99 divisions: B02 divisions: UCL divisions: D19 keywords: CD142, adipogenesis regulators (Aregs), adipose stem and precursor cells, differentiation, retinoic acid note: 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. 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. date: 2022-08-22 date_type: published publisher: EMBO official_url: https://doi.org/10.15252/embj.2021108206 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1972979 doi: 10.15252/embj.2021108206 medium: Print-Electronic lyricists_name: Litovchenko, Maria lyricists_id: MLITO41 actors_name: Flynn, Bernadette actors_id: BFFLY94 actors_role: owner funding_acknowledgements: #222 [Precise and Health-related Technologies Initiative Grants (PHRT)]; #307 [Precise and Health-related Technologies Initiative Grants (PHRT)]; #502 [Precise and Health-related Technologies Initiative Grants (PHRT)]; 31003A_162735 [Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (SNF)]; 31003A_182655 [Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (SNF)]; CRSII5_186271 [Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (SNF)]; [Swiss Federal Institute of Technology in Lausanne (EPFL)] full_text_status: public publication: The EMBO Journal article_number: e108206 event_location: England issn: 0261-4189 citation: Zachara, Magda; Rainer, Pernille Y; Hashimi, Horia; Russeil, Julie M; Alpern, Daniel; Ferrero, Radiana; Litovchenko, Maria; Zachara, Magda; Rainer, Pernille Y; Hashimi, Horia; Russeil, Julie M; Alpern, Daniel; Ferrero, Radiana; Litovchenko, Maria; Deplancke, Bart; - view fewer <#> (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 <https://doi.org/10.15252/embj.2021108206>. (In press). Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10154771/1/The%20EMBO%20Journal%20-%202022%20-%20Zachara.pdf