Transcriptional Pathways in cPGI2-Induced Adipocyte Progenitor Activation for Browning
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/109148 https://doi.org/10.3389/fendo.2015.00129 |
Resumo: | De novo formation of beige/brite adipocytes from progenitor cells contributes to the thermogenic adaptation of adipose tissue and holds great potential for the therapeutic remodeling of fat as a treatment for obesity. Despite the recent identification of several factors regulating browning of white fat, there is a lack of physiological cell models for the mechanistic investigation of progenitor-mediated beige/brite differentiation. We have previously revealed prostacyclin (PGI2) as one of the few known endogenous extracellular mediators promoting de novo beige/brite formation by relaying β-adrenergic stimulation to the progenitor level. Here, we present a cell model based on murine primary progenitor cells defined by markers previously shown to be relevant for in vivo browning, including a simplified isolation procedure. We demonstrate the specific and broad induction of thermogenic gene expression by PGI2 signaling in the absence of lineage conversion, and reveal the previously unidentified nuclear relocalization of the Ucp1 gene locus in association with transcriptional activation. By profiling the time course of the progenitor response, we show that PGI2 signaling promoted progenitor cell activation through cell cycle and adhesion pathways prior to metabolic maturation toward an oxidative cell phenotype. Our results highlight the importance of core progenitor activation pathways for the recruitment of thermogenic cells and provide a resource for further mechanistic investigation. |
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Transcriptional Pathways in cPGI2-Induced Adipocyte Progenitor Activation for Browningbeige/brite differentiationadipocyte progenitorsprostacyclinPGI2adipocyte cell modeladipose tissue remodelingnuclear localizationDe novo formation of beige/brite adipocytes from progenitor cells contributes to the thermogenic adaptation of adipose tissue and holds great potential for the therapeutic remodeling of fat as a treatment for obesity. Despite the recent identification of several factors regulating browning of white fat, there is a lack of physiological cell models for the mechanistic investigation of progenitor-mediated beige/brite differentiation. We have previously revealed prostacyclin (PGI2) as one of the few known endogenous extracellular mediators promoting de novo beige/brite formation by relaying β-adrenergic stimulation to the progenitor level. Here, we present a cell model based on murine primary progenitor cells defined by markers previously shown to be relevant for in vivo browning, including a simplified isolation procedure. We demonstrate the specific and broad induction of thermogenic gene expression by PGI2 signaling in the absence of lineage conversion, and reveal the previously unidentified nuclear relocalization of the Ucp1 gene locus in association with transcriptional activation. By profiling the time course of the progenitor response, we show that PGI2 signaling promoted progenitor cell activation through cell cycle and adhesion pathways prior to metabolic maturation toward an oxidative cell phenotype. Our results highlight the importance of core progenitor activation pathways for the recruitment of thermogenic cells and provide a resource for further mechanistic investigation.Frontiers Media S.A.2015info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/109148http://hdl.handle.net/10316/109148https://doi.org/10.3389/fendo.2015.00129eng1664-2392Bayindir, IremBabaeikelishomi, RohollahKocanova, SilviaSousa, Isabel SofiaLerch, SarahHardt, OlafWild, StefanBosio, AndreasBystricky, KerstinHerzig, StephanVegiopoulos, Alexandrosinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-09-29T08:08:37Zoai:estudogeral.uc.pt:10316/109148Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:25:20.806774Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Transcriptional Pathways in cPGI2-Induced Adipocyte Progenitor Activation for Browning |
title |
Transcriptional Pathways in cPGI2-Induced Adipocyte Progenitor Activation for Browning |
spellingShingle |
Transcriptional Pathways in cPGI2-Induced Adipocyte Progenitor Activation for Browning Bayindir, Irem beige/brite differentiation adipocyte progenitors prostacyclin PGI2 adipocyte cell model adipose tissue remodeling nuclear localization |
title_short |
Transcriptional Pathways in cPGI2-Induced Adipocyte Progenitor Activation for Browning |
title_full |
Transcriptional Pathways in cPGI2-Induced Adipocyte Progenitor Activation for Browning |
title_fullStr |
Transcriptional Pathways in cPGI2-Induced Adipocyte Progenitor Activation for Browning |
title_full_unstemmed |
Transcriptional Pathways in cPGI2-Induced Adipocyte Progenitor Activation for Browning |
title_sort |
Transcriptional Pathways in cPGI2-Induced Adipocyte Progenitor Activation for Browning |
author |
Bayindir, Irem |
author_facet |
Bayindir, Irem Babaeikelishomi, Rohollah Kocanova, Silvia Sousa, Isabel Sofia Lerch, Sarah Hardt, Olaf Wild, Stefan Bosio, Andreas Bystricky, Kerstin Herzig, Stephan Vegiopoulos, Alexandros |
author_role |
author |
author2 |
Babaeikelishomi, Rohollah Kocanova, Silvia Sousa, Isabel Sofia Lerch, Sarah Hardt, Olaf Wild, Stefan Bosio, Andreas Bystricky, Kerstin Herzig, Stephan Vegiopoulos, Alexandros |
author2_role |
author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Bayindir, Irem Babaeikelishomi, Rohollah Kocanova, Silvia Sousa, Isabel Sofia Lerch, Sarah Hardt, Olaf Wild, Stefan Bosio, Andreas Bystricky, Kerstin Herzig, Stephan Vegiopoulos, Alexandros |
dc.subject.por.fl_str_mv |
beige/brite differentiation adipocyte progenitors prostacyclin PGI2 adipocyte cell model adipose tissue remodeling nuclear localization |
topic |
beige/brite differentiation adipocyte progenitors prostacyclin PGI2 adipocyte cell model adipose tissue remodeling nuclear localization |
description |
De novo formation of beige/brite adipocytes from progenitor cells contributes to the thermogenic adaptation of adipose tissue and holds great potential for the therapeutic remodeling of fat as a treatment for obesity. Despite the recent identification of several factors regulating browning of white fat, there is a lack of physiological cell models for the mechanistic investigation of progenitor-mediated beige/brite differentiation. We have previously revealed prostacyclin (PGI2) as one of the few known endogenous extracellular mediators promoting de novo beige/brite formation by relaying β-adrenergic stimulation to the progenitor level. Here, we present a cell model based on murine primary progenitor cells defined by markers previously shown to be relevant for in vivo browning, including a simplified isolation procedure. We demonstrate the specific and broad induction of thermogenic gene expression by PGI2 signaling in the absence of lineage conversion, and reveal the previously unidentified nuclear relocalization of the Ucp1 gene locus in association with transcriptional activation. By profiling the time course of the progenitor response, we show that PGI2 signaling promoted progenitor cell activation through cell cycle and adhesion pathways prior to metabolic maturation toward an oxidative cell phenotype. Our results highlight the importance of core progenitor activation pathways for the recruitment of thermogenic cells and provide a resource for further mechanistic investigation. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/109148 http://hdl.handle.net/10316/109148 https://doi.org/10.3389/fendo.2015.00129 |
url |
http://hdl.handle.net/10316/109148 https://doi.org/10.3389/fendo.2015.00129 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1664-2392 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Frontiers Media S.A. |
publisher.none.fl_str_mv |
Frontiers Media S.A. |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799134136429969408 |