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GEO help: Mouse over screen elements for information. |
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Status |
Public on Nov 12, 2024 |
Title |
Collagen signaling and matrix stiffness regulate multipotency in glandular epithelial stem cells in mice [scRNA-Seq] |
Organism |
Mus musculus |
Experiment type |
Other
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Summary |
Glandular epithelia, including mammary gland (MG) and prostate, are composed of luminal and basal cells. During embryonic development, glandular epithelia arise from multipotent stem cells (SCs) giving rise to basal and luminal cells. However, these multipotent SCs are replaced after birth by unipotent basal and unipotent luminal SCs. Different conditions, such as basal cell transplantation, luminal cell ablation, and oncogene expression, can reinduce multipotency in adult basal SC (BaSCs) of different glandular epithelia. The mechanisms regulating the reactivation of multipotency in BaSCs are incompletely understood. Here, we compared the transcriptional signature of BaSCs from MG and prostate in different conditions associated with multipotency in adult mice and uncovered that Collagen I expression was commonly upregulated across the different conditions associated with multipotency. Using MG and prostate organoids, we demonstrated that increasing collagen concentration or stiffness of the extracellular matrix (ECM) promote BaSC multipotency. Single cell RNA-seq of MG organoids in the presence of high concentration of Collagen I or in a stiffer ECM activate a hybrid bipotent state and uncovered a gene signature and signaling pathways associated with bipotent BaSCs. Finally, we demonstrated the importance of 1integrin/FAK/AP-1 axis in the regulation of BaSC multipotency in response to Col1 signaling and ECM stiffness. Altogether our study uncovers the key role of Collagen signaling and ECM stiffness in the regulation of multipotency in glandular epithelia.
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Overall design |
The mammary gland organoid from fat pads of 8-to-9-week-old virgin mice without lymph nodes were cultured under different stiffness and analysed using scRNA-seq.
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Contributor(s) |
Blanpain C, Centonze A, Song Y, Jiang C |
Citation(s) |
39695111 |
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Submission date |
Sep 15, 2023 |
Last update date |
Jan 30, 2025 |
Contact name |
Yura Song |
E-mail(s) |
yura.song@ulb.be
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Organization name |
Université Libre de Bruxelles
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Lab |
Laboratory of Stem Cells and Cancer
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Street address |
808, route de Lennik
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City |
Bruxelles |
ZIP/Postal code |
1070 |
Country |
Belgium |
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Platforms (1) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (4)
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This SubSeries is part of SuperSeries: |
GSE243338 |
Collagen signaling and matrix stiffness regulate multipotency in glandular epithelial stem cells in mice |
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Relations |
BioProject |
PRJNA1017846 |
Supplementary file |
Size |
Download |
File type/resource |
GSE243335_RAW.tar |
422.0 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
Raw data are available in SRA |
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