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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Mar 24, 2024 |
| Title |
Isthmus progenitor cells contribute to homeostatic cellular turnover and support regeneration following intestinal injury |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The currently accepted intestinal epithelial cell organization model equates crypt base columnar (CBC) cells, marked by high levels of Lgr5 expression, with the intestinal stem cell (ISC). However, recent intestinal regeneration studies have uncovered limitations of the ‘Lgr5-CBC’ model, leading to two major views: one favoring the presence of a quiescent reserve stem cell population, the other calling for differentiated cell plasticity. To test if an alternative model may help reconcile these perspectives, we studied the hierarchical organization of crypt epithelial cells in an unbiased fashion, by combining high-resolution, single-cell profiling and lineage tracing in multiple transgenic mouse models. These show that Lgr5 is not a specific ISC marker; rather, cells located in the crypt isthmus, which include Lgr5low cells, comprise the ISCs that sustain tissue homeostasis. Following irradiation or intestinal injury, surviving ISCs and progenitors, but not differentiated cells, participate in intestinal regeneration, suggesting that neither de-differentiation nor reserve stem cell populations are drivers of intestinal regeneration. Our results provide a novel viewpoint for the intestinal crypt epithelium, in which ISCs localize to the crypt isthmus, and ISC potential is restricted to stem and progenitor cells.
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| Overall design |
Single-cell RNA-Seq data of highly purified mouse intestinal crypt epithelial cells
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| Contributor(s) |
Malagola E, Vasciaveo A, Califano A, Wang TC |
| Citation(s) |
38848678 |
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| Submission date |
May 31, 2022 |
| Last update date |
Jun 27, 2024 |
| Contact name |
Alessandro Vasciaveo |
| E-mail(s) |
av2729@cumc.columbia.edu
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| Organization name |
Columbia University
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| Department |
Department of Systems Biology
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| Street address |
1130 Saint Nicholas Ave., 910
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| City |
New York City |
| State/province |
NY |
| ZIP/Postal code |
10032 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (6)
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| GSM6208863 |
Mouse intestinal crypt epithelial cells from adult male C57BL/6J (8 weeks old), untreated, scRNA-seq |
| GSM6208864 |
Mouse intestinal crypt epithelial cells from adult male C57BL/6J (8 weeks old), 60 hours post IR-damage, scRNA-seq |
| GSM6208865 |
Mouse intestinal crypt epithelial cells from adult male Lgr5-DTR-eGFP (8 weeks old), untreated, scRNA-seq |
| GSM6208866 |
Mouse intestinal crypt epithelial cells from adult male Lgr5-DTR-eGFP (8 weeks old), DT treated, scRNA-seq |
| GSM6208867 |
Mouse intestinal crypt epithelial cells from adult male C57BL/6J (8 weeks old), untreated snRNA-seq (multiome) |
| GSM6208868 |
Mouse intestinal crypt epithelial cells from adult male C57BL/6J (8 weeks old), untreated, snATAC-seq (multiome) |
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| Relations |
| BioProject |
PRJNA844124 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE205229_RAW.tar |
1.0 Gb |
(http)(custom) |
TAR (of H5, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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