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Series GSE127975 Query DataSets for GSE127975
Status Public on Apr 24, 2020
Title Heterotypic cell-cell communication regulates multipotency in glandular epithelial stem cells
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Glandular epithelia including the mammary gland (MG) and the prostate are composed of basal cells (BC) and luminal cells (LC). Lineage tracing demonstrates that many glandular epithelia initially develop from multipotent basal stem cells (BaSCs) that are replaced in adult life by distinct pool of unipotent stem cells (SCs). However, adult unipotent BaSC can reactivate multipotency and give rise to LCs upon transplantation or oncogene expression, demonstrating the important plasticity of BaSCs in regenerative and pathological conditions, and suggesting that an active mechanism restricts multipotency in BaSCs during physiological conditions. The nature of this mechanism is currently unknown. Here, we assess whether basal and luminal cell-cell communication restricts multipotency in glandular epithelia. To this end, we performed lineage tracing of BCs together with the ablation of LCs in different adult glandular epithelia including MG, prostate, sweat glands and salivary glands and assessed the fate of BaSCs overtime. Interestingly, ablation of LCs reactivated multipotency in unipotent adult BaSCs from multiple epithelia. To understand the molecular mechanisms that controls multipotency in adult BaSCs, we performed population bulk-RNA-seq and single cell RNA-seq of FACS isolated adult mammary epithelial cells after LC ablation. Upon LC ablation, adult BCs activate a hybrid basal and luminal differentiation program before giving rise to LC, reminiscent of the genetic program that regulate multipotency during embryonic development. Different signaling pathways including Notch, Wnt and Egfr were activated in BaSC and their progeny following LC ablation and blocking these pathways inhibited adult BC multipotency. Altogether, our study demonstrates that heterotypic LC and BC communication is essential to maintain lineage fidelity in glandular epithelial SC during homeostasis and uncovers the lineage trajectory and signaling pathways that promote multipotency during tissue repair.
Overall design Bulk RNAseq of FACS-sorted mammary gland isolated cells.
Contributor(s) Centonze C, Centonze A, Lin S, Song Y
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Submission date Mar 06, 2019
Last update date Apr 26, 2020
Contact name Alessia Centonze
Organization name Université libre de Bruxelles
Lab Laboratory of Stem cell and Cancer
Street address Route de Lennik 808
City Bruxelles
ZIP/Postal code 1070
Country Belgium
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (10)
GSM3659355 BC_S44
GSM3659356 LC_S45
GSM3659357 TBC_S46
BioProject PRJNA525897
SRA SRP187787

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Supplementary file Size Download File type/resource
GSE127975_RAW.tar 1.8 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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