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Series GSE178109 Query DataSets for GSE178109
Status Public on Jan 30, 2023
Title Indian Hedgehog release from inflamed epithelia links TNF-alpha to organ fibrosis
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary In chronic kidney disease (CKD) and with ageing, individuals lose regenerative capacity after renal injury and are predisposed to progressive fibrosis and cardiovascular disease. With ageing and CKD increased numbers of activated leukocytes are present in the circulation and within the kidney where they correlate with progressive fibrosis. The potential role of activated leukocytes in mediating progressive renal and systemic fibrosis remains incompletely understood. Here, we show that tumour necrosis factor alpha (TNFa) released with injury and aging promotes renal and cardiac fibrosis. We identify a Ubiquitin D expressing population of TNFa induced inflammatory proximal tubular epithelia (iPT) responsible for Indian Hedgehog release in aged and fibrotic kidneys. Indian Hedgehog production by iPT cells activates canonical Hedgehog signalling in Gli1+ stromal cells leading to activation, proliferation and fibrosis deposition. Our data links the immune activation seen in aging and chronic kidney disease to cardio-renal fibrosis. This provides multiple targets for antifibrotic therapies which we validate in murine models of aging and kidney disease.
 
Overall design Unbiased examination of single cell RNA-seq of injured murine kidney, control kidneys and BULK RNA-SEQ of IHH KO kidneys, paired controls, uninjured controls, post nephrectomy contralatearl kidneys , and post iri contralateral
 
Contributor(s) O'Sullivan E, Ferenbach D
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Submission date Jun 14, 2021
Last update date Jan 30, 2023
Contact name Eoin D O'Sullivan
E-mail(s) eoindosullivan@gmail.com
Organization name University of Edinburgh
Department Centre for Inflammation Research
Lab Edinburgh BioQuarter
Street address 47 Little France Crescent
City Edinburgh
ZIP/Postal code EH16 4TJ
Country United Kingdom
 
Platforms (1)
GPL21626 NextSeq 550 (Mus musculus)
Samples (10)
GSM5380284 IRI_MOUSE_SC
GSM5380285 UNINJURED_MOUSE_SC
GSM5380286 IRI.TG.TAM
Relations
BioProject PRJNA737404
SRA SRP323944

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE178109_IRI_sc_counts.csv.gz 4.1 Mb (ftp)(http) CSV
GSE178109_bulk_matrix.csv.gz 6.2 Mb (ftp)(http) CSV
GSE178109_uninjured_sc_counts.csv.gz 1.8 Mb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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