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| 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
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| 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.
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| 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).
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| 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
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| Department |
II. Medizinische Klinik
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| Street address |
Ismaninger Str. 22
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| City |
Munich |
| State/province |
Bavaria |
| ZIP/Postal code |
81675 |
| Country |
Germany |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA575638 |
| SRA |
SRP224064 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE138365_TC-Scopolamine-Experiment-RawCounts.txt.gz |
343.6 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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