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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jun 07, 2022 |
| Title |
Cell and chromatin transitions in intestinal stem cell regeneration |
| 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 progeny of intestinal stem cells (ISCs) dedifferentiate in response to ISC attrition. The precise cell sources, transitional states, and chromatin remodeling behind this activity remain unclear. In the skin, stem cell recovery after injury preserves an epigenetic memory of the damage response; whether similar memories arise and persist in regenerated ISCs is not known. We address these questions by examining gene activity and open chromatin at the resolution of single Neurog3-labeled mouse intestinal crypt cells, hence deconstructing forward and reverse differentiation of the intestinal secretory (Sec) lineage. We show that goblet, Paneth, and enteroendocrine cells arise by multilineage priming in common precursors, followed by selective access at thousands of cell-restricted cis-elements. Selective ablation of the ISC compartment elicits speedy reversal of chromatin and transcriptional features in large fractions of precursor and mature crypt Sec cells without obligate cell cycle re-entry. ISC programs decay and reappear along a cellular continuum lacking discernible discrete interim states. In the absence of gross tissue damage, Sec cells simply reverse their forward trajectories, without invoking developmental or other extrinsic programs, and starting chromatin identities are effectively erased. These findings identify strikingly plastic molecular frameworks in assembly and regeneration of a self-renewing tissue.
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| Overall design |
ScRNA-seq and scATAC-seq profiles of Neurog3 traced tomato positive cells, after two daily doses of TAM, at 12h, 24h, 48h, 72h from Ngn3CreERT2;R26tdtomato;Lgr5-DTRGFP mice and Neurog3 traced cells after stem cell ablation, via DT injection, at 12h, 24h, 48h and 72h from Ngn3CreERT2;R26tdtomato;Lgr5-DTRGFP mice
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| Contributor(s) |
Singh PN, Madha S, Leiter AB, Shivdasani RA |
| Citation(s) |
35738677 |
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| Submission date |
Sep 02, 2021 |
| Last update date |
Jun 28, 2022 |
| Contact name |
Ramesh Shivdasani |
| E-mail(s) |
ramesh_shivdasani@dfci.harvard.edu
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| Organization name |
Dana Farber Cancer Institute
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| Department |
Medical Oncology
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| Lab |
Shivdasani
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| Street address |
450 Brookline Ave. Dana 720D
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02215 |
| Country |
USA |
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| Platforms (2) |
| GPL21273 |
HiSeq X Ten (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (22)
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| Relations |
| BioProject |
PRJNA759894 |
| SRA |
SRP335418 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE183299_RAW.tar |
2.9 Gb |
(http)(custom) |
TAR (of BW, ZIP) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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