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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 02, 2019 |
| Title |
A large pool of actively cycling progenitors orchestrates self-renewal and injury repair of an ectodermal appendage |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The classical model posits that a small number of quiescent stem cells (SCs) gives rise to proliferating transit-amplifying cells before terminal differentiation. However, recent evidence indicates that some tissues house multiple progenitor pools with distinct proliferative and differentiation potentials. Resolving the identity and spatial organization of these populations is therefore a fundamental requirement for understanding tissue renewal. Here, using a combination of single-cell RNA sequencing (scRNAseq), mouse genetics, and tissue injury approaches, we uncovered cellular hierarchies and mechanisms underlying the maintenance and repair of the ever-growing mouse incisor, an ectodermal appendage model system that requires high cell turnover for its homeostasis and quick healing capability. We found that during homeostasis, a group of actively cycling epithelial progenitors generates both the enamel-producing ameloblasts and the adjacent non-ameloblast cell layers, which were previously proposed to be quiescent SCs. Upon injury, transient adjustments to the proliferation kinetics of dental epithelial progenitor cells compensated for cell loss. Injury repair was also supported by direct conversion of supporting Notch1-expressing cells to ameloblasts. Our elucidation of epithelial SC identity, position, and function thus provides a mechanistic basis for the homeostasis and repair of a fast-turnover ectodermal appendage and illustrates how a cycling progenitor pool confers considerable epithelial plasticity during tissue renewal.
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| Overall design |
Single cell RNA sequencing of mouse incisor growth region EPCAM+ cells under two conditions: 1) homeostasis (5 mice pooled into one sample); 2) 3-days post-injury with 5- fluorouracil (5 mice pooled into one sample).
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| Contributor(s) |
Sharir A, Marangoni P, Zilionis R, Wan M, Wald T, Hu J, Kawaguchi K, Castillo-Azofeifa D, Epstein L, Harrington K, Pagella P, Mitsiadis T, Siebel CW, Klein AM, Klein OD |
| Citation(s) |
31481792 |
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| Submission date |
May 14, 2019 |
| Last update date |
Oct 07, 2019 |
| Contact name |
Rapolas Zilionis |
| E-mail(s) |
rapolas.zilionis@bti.vu.lt
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| Organization name |
Vilnius University
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| Department |
Life Sciences Center
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| Lab |
Mazutis
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| Street address |
Sauletekis av 7
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| City |
Vilnius |
| State/province |
LT |
| ZIP/Postal code |
10257 |
| Country |
Lithuania |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA542894 |
| SRA |
SRP198395 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE131204_RAW.tar |
145.4 Mb |
(http)(custom) |
TAR (of HDF5, MTX, TSV) |
| GSE131204_average_gene_expression_per_population.tsv.gz |
1.8 Mb |
(ftp)(http) |
TSV |
| GSE131204_cell_info_8594x25.tsv.gz |
533.9 Kb |
(ftp)(http) |
TSV |
| GSE131204_gene_names_alphabetically.txt.gz |
71.5 Kb |
(ftp)(http) |
TXT |
| GSE131204_raw_counts_8594x27998.mtx.gz |
50.0 Mb |
(ftp)(http) |
MTX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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