Luminal Rank loss decreases cell fitness leading to basal cell bipotency in parous mammary glands

Rank signaling pathway regulates mammary gland homeostasis and epithelial cell differentiation. Although Rank receptor is expressed by basal cells and luminal progenitors, its role in each individual cell lineage remains unclear. By combining temporal/lineage specific Rank genetic deletion with line...

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Autores: Rocha, Ana Sofia, Collado Solé, Alejandro, Graña Castro, Osvaldo, Redondo Pedraza, Jaime, Soria Alcaide, Gonzalo, Cordero, Alex, Santamaría, Patricia G., González Suárez, Eva
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/204384
Acesso em linha:https://hdl.handle.net/2445/204384
Access Level:acceso abierto
Palavra-chave:Homeòstasi
Glàndules mamàries
Homeostasis
Mammary glands
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spelling Luminal Rank loss decreases cell fitness leading to basal cell bipotency in parous mammary glandsRocha, Ana SofiaCollado Solé, AlejandroGraña Castro, OsvaldoRedondo Pedraza, JaimeSoria Alcaide, GonzaloCordero, AlexSantamaría, Patricia G.González Suárez, EvaHomeòstasiGlàndules mamàriesHomeostasisMammary glandsRank signaling pathway regulates mammary gland homeostasis and epithelial cell differentiation. Although Rank receptor is expressed by basal cells and luminal progenitors, its role in each individual cell lineage remains unclear. By combining temporal/lineage specific Rank genetic deletion with lineage tracing techniques, we found that loss of luminal Rank reduces the luminal progenitor pool and leads to aberrant alveolar-like differentiation with high protein translation capacity in virgin mammary glands. These Rank-deleted luminal cells are unable to expand during the first pregnancy, leading to lactation failure and impairment of protein synthesis potential in the parous stage. The unfit parous Rank-deleted luminal cells in the alveoli are progressively replaced by Rank-proficient cells early during the second pregnancy, thereby restoring lactation. Transcriptomic analysis and functional assays point to the awakening of basal bipotency after pregnancy by the induction of Rank/NF-kappa B signaling in basal parous cell to restore lactation and tissue homeostasis. Rocha and co-authors show that loss of luminal Rank signaling causes abnormal alveolar differentiation and lactation failure. Subsequent pregnancies activate bipotency in basal cells, replacing unfit luminal cells, and restoring lactation.Springer Science and Business Media LLC2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/204384Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1038/s41467-023-41741-5Nature Communications, 2023, vol. 14, num. 1https://doi.org/10.1038/s41467-023-41741-5cc by (c) Rocha, Ana Sofia et al, 2023http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2043842026-05-27T06:46:51Z
dc.title.none.fl_str_mv Luminal Rank loss decreases cell fitness leading to basal cell bipotency in parous mammary glands
title Luminal Rank loss decreases cell fitness leading to basal cell bipotency in parous mammary glands
spellingShingle Luminal Rank loss decreases cell fitness leading to basal cell bipotency in parous mammary glands
Rocha, Ana Sofia
Homeòstasi
Glàndules mamàries
Homeostasis
Mammary glands
title_short Luminal Rank loss decreases cell fitness leading to basal cell bipotency in parous mammary glands
title_full Luminal Rank loss decreases cell fitness leading to basal cell bipotency in parous mammary glands
title_fullStr Luminal Rank loss decreases cell fitness leading to basal cell bipotency in parous mammary glands
title_full_unstemmed Luminal Rank loss decreases cell fitness leading to basal cell bipotency in parous mammary glands
title_sort Luminal Rank loss decreases cell fitness leading to basal cell bipotency in parous mammary glands
dc.creator.none.fl_str_mv Rocha, Ana Sofia
Collado Solé, Alejandro
Graña Castro, Osvaldo
Redondo Pedraza, Jaime
Soria Alcaide, Gonzalo
Cordero, Alex
Santamaría, Patricia G.
González Suárez, Eva
author Rocha, Ana Sofia
author_facet Rocha, Ana Sofia
Collado Solé, Alejandro
Graña Castro, Osvaldo
Redondo Pedraza, Jaime
Soria Alcaide, Gonzalo
Cordero, Alex
Santamaría, Patricia G.
González Suárez, Eva
author_role author
author2 Collado Solé, Alejandro
Graña Castro, Osvaldo
Redondo Pedraza, Jaime
Soria Alcaide, Gonzalo
Cordero, Alex
Santamaría, Patricia G.
González Suárez, Eva
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Homeòstasi
Glàndules mamàries
Homeostasis
Mammary glands
topic Homeòstasi
Glàndules mamàries
Homeostasis
Mammary glands
description Rank signaling pathway regulates mammary gland homeostasis and epithelial cell differentiation. Although Rank receptor is expressed by basal cells and luminal progenitors, its role in each individual cell lineage remains unclear. By combining temporal/lineage specific Rank genetic deletion with lineage tracing techniques, we found that loss of luminal Rank reduces the luminal progenitor pool and leads to aberrant alveolar-like differentiation with high protein translation capacity in virgin mammary glands. These Rank-deleted luminal cells are unable to expand during the first pregnancy, leading to lactation failure and impairment of protein synthesis potential in the parous stage. The unfit parous Rank-deleted luminal cells in the alveoli are progressively replaced by Rank-proficient cells early during the second pregnancy, thereby restoring lactation. Transcriptomic analysis and functional assays point to the awakening of basal bipotency after pregnancy by the induction of Rank/NF-kappa B signaling in basal parous cell to restore lactation and tissue homeostasis. Rocha and co-authors show that loss of luminal Rank signaling causes abnormal alveolar differentiation and lactation failure. Subsequent pregnancies activate bipotency in basal cells, replacing unfit luminal cells, and restoring lactation.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/204384
url https://hdl.handle.net/2445/204384
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1038/s41467-023-41741-5
Nature Communications, 2023, vol. 14, num. 1
https://doi.org/10.1038/s41467-023-41741-5
dc.rights.none.fl_str_mv cc by (c) Rocha, Ana Sofia et al, 2023
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Rocha, Ana Sofia et al, 2023
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer Science and Business Media LLC
publisher.none.fl_str_mv Springer Science and Business Media LLC
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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