2026-06-14T02:29:18Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/191182024-11-29T15:41:03Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Rocha, Ana Sofia
author
Collado-Solé, Alejandro
author
Graña-Castro, Osvaldo
author
Redondo-Pedraza, Jaime
author
Soria-Alcaide, Gonzalo
author
Cordero, Alex
author
Santamaría, Patricia G
author
González-Suárez, Eva
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Ministerio de Ciencia e Innovación (España)
2024-04-04T11:49:37Z
2024-04-04T11:49:37Z
2023-10-09
Nat Commun. 2023;14(1):6213.
10.1038/s41467-023-41741-5
2041-1723
Nature communications
37813842
http://hdl.handle.net/20.500.12105/19118
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-κB signaling in basal parous cell to restore lactation and tissue homeostasis.
eng
Luminal Rank loss decreases cell fitness leading to basal cell bipotency in parous mammary glands.
journal article
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
URL
https://repisalud.isciii.es/bitstreams/70061459-ec1b-4a2d-a3fc-ab159b5be579/download
File
MD5
7eb5ae0919362ca2c946ae24541acf66
9096338
application/pdf
LuminalRanklossdecreases_2023.pdf
URL
https://repisalud.isciii.es/bitstreams/8a840de5-a350-459c-9ac6-b2b3b93162c2/download
File
MD5
aea7fa6f35a95a28d0568c9611d3e1a9
37349089
application/pdf
41467_2023_41741_MOESM1_ESM.pdf
URL
https://repisalud.isciii.es/bitstreams/0ca4f764-4b9b-440f-9a12-0d7dd700a505/download
File
MD5
2cde362792daf1cdd3571ee24eb53155
186153
application/pdf
41467_2023_41741_MOESM2_ESM.pdf
URL
https://repisalud.isciii.es/bitstreams/2a366b6b-2c6e-4dc4-bb38-f917a0a65eb5/download
File
MD5
626a69e795698ec021cd52923ab67035
3523095
application/pdf
41467_2023_41741_MOESM8_ESM.pdf
URL
https://repisalud.isciii.es/bitstreams/ee4b2ce0-5563-4070-a1ff-deac3ab27b05/download
File
MD5
a573b529efe813cff082be135da71c85
67786
text/plain
LuminalRanklossdecreases_2023.pdf.txt
URL
https://repisalud.isciii.es/bitstreams/0ee16820-f817-46d2-99c8-e369bee4d83b/download
File
MD5
dcde8891814bb863bc95ec4eb1a4611f
12605
text/plain
41467_2023_41741_MOESM1_ESM.pdf.txt
URL
https://repisalud.isciii.es/bitstreams/3e4eaa0a-ee4f-4337-9392-40a0551508ab/download
File
MD5
532c29959c60b934f309b2ac45ef4ec1
2124
text/plain
41467_2023_41741_MOESM2_ESM.pdf.txt
URL
https://repisalud.isciii.es/bitstreams/7a6bee22-9f76-4972-ae24-1273d056243d/download
File
MD5
bd5814c83dcc185f4d36779880a55f4d
11
text/plain
41467_2023_41741_MOESM8_ESM.pdf.txt