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Series GSE138365 Query DataSets for GSE138365
Status Public on Nov 01, 2019
Title Gene expression from tuft cells under scopolamine treatment
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary In our study, we investigated the effect of muscarinic receptor blockade on murine intestinal stem cell activity and differentiation. Following pharmacologic (scopolamine) and genetic muscarinic receptor interruption (M3R-KO, M1R-KO; Vil-Cre x M3R fl/fl, Vil-Cre x M1R fl/fl mice, respectively), we observe a selective, significant expansion of DCLK1-positive tuft cells. This is primarily sensed by endocrine Prox1-positive cells (Prox1-CreERT2 x M3R fl/fl mice), while Lgr5-positive ISCs respond with a reduction of their cellular activity (Lgr5-EGFP-IRES-CreERT2 x M3R fl/fl mice). To characterize expanding tuft cells in more detail, adult BAC transgenic DCLK1-DTR-ZSgreen reporter mice generated in our lab were treated with scopolamine or sodium chloride as controls (Sham) for 7d and live jejunal EPC-positive/ZSgreen-positive cells sorted. Extracted total RNA from sorted ZSgreen-positive cells of scopolamine- and sham-treated mice was sequenced. Further analysis revealed that expanding tuft cells orchestrate an increase in mucosal acetylcholine, which maintained intracellular signaling pathways such as p-ERK/ERK 1/2 or TCF-1/7. Finally, acute irradiation injury was employed to investigate the importance of this regulatory circuit for tissue homeostasis. Indeed, tissue injury in Vil-Cre x M3R fl/fl mice resulted in a severe reduction of epithelial DCLK1-positive tuft cells, concomitant to reduced mucosal Ach levels as well as intracellular PI3K-/p-ERK levels. Therefore, DCLK1-positive tuft cells appear essential for the maintenance of a regular intestinal cholinergic niche.
Overall design Bulk gene expression data are presented for sorted DCLK1-DTR-ZSgreen-positive cells from scopolamine treated mice (n=4) or sham treated mice (n=4).
Contributor(s) Middelhoff M, Nienhüser H, Maurer HC, Wang TC
Citation(s) 31913277
Submission date Oct 03, 2019
Last update date Jan 21, 2020
Contact name Hans Carlo Maurer
Organization name Klinikum rechts der Isar
Department II. Medizinische Klinik
Street address Ismaninger Str. 22
City Munich
State/province Bavaria
ZIP/Postal code 81675
Country Germany
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (8)
GSM4106036 WH001
GSM4106037 WH002
GSM4106038 WH003
BioProject PRJNA575638
SRA SRP224064

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Supplementary file Size Download File type/resource
GSE138365_TC-Scopolamine-Experiment-RawCounts.txt.gz 343.6 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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