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Series GSE139272 Query DataSets for GSE139272
Status Public on Dec 16, 2020
Title Genotoxicity induces epithelial hyperplasia and lineage infidelity via fibroblast IL-1β
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Epithelial tissues possess a barrier function that must be restored following injury. Repair often involves changes in cell fate, but it remains poorly understood how cell plasticity is induced and whether responses vary with distinct types of damage. Here, we reveal that genotoxic agents, but not mechanical damage, induce hyperplasia and lineage infidelity in the interfollicular epidermis, as well as in two epidermal subappendages: the mammary gland and hair follicle. DNA damage to the epidermis promotes stromal proliferation, and induces basal cell hyperplasia with formation of abnormal, multi-layered K14+/K10+ cells. Unexpectedly, this behavior is epithelial cell non-autonomous, but independent of immunity. Instead, dermal fibroblasts are both necessary and sufficient to induce the epithelial response. We identify a previously unrecognized fibroblast-specific NLRP3 inflammasome that drives this response via IL-1β. Thus, genotoxic agents, used chemotherapeutically to promote cancer cell death, can have the opposite effect on wild-type epithelia, paradoxically promoting hyperplasia and inducing both stemness and lineage infidelity via a non-autonomous, fibroblast-driven mechanism.
Overall design Analysis of gene expression changes in dermal fibroblasts following Cisplatin treatment; 2 vehicle replicates, 2 Cisplatin replicates
Contributor(s) Seldin L, Macara I
Citation(s) 33058780
Submission date Oct 22, 2019
Last update date Dec 16, 2020
Contact name Lindsey Seldin
Organization name Vanderbilt University
Street address 465 21st Avenue South U3200 MRBIII
City Nashville
ZIP/Postal code 37240-7935
Country USA
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (4)
GSM4135896 Vehicle rep1
GSM4135897 Vehicle rep2
GSM4135898 Cisplatin rep1
BioProject PRJNA578953
SRA SRP226661

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Supplementary file Size Download File type/resource
GSE139272_Differential_Expression__Cisplatin_vs._Vehicle.xlsx 2.9 Mb (ftp)(http) XLSX
GSE139272_RAW.tar 65.7 Mb (http)(custom) TAR (of XLSX)
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Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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