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| Status |
Public on Nov 22, 2016 |
| Title |
p53 is a critical regulator of airway epithelial progenitor cell homeostasis. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
How progenitor cells regulate quiescence and differentiation is poorly understood. Here, we demonstrate that the tumor suppressor p53 regulates both proliferation and differentiation of club progenitor cells in the airway epithelium. We show that p53 loss decreases ciliated cell differentiation and increases the proliferative capacity of club progenitors, increasing epithelial cell density. p53 deficient progenitors generated a pseudostratified epithelium containing basal-like cells in vitro and contained an increased proportion of BASCs in vivo, suggesting that p53 suppresses multipotency during homeostasis. Conversely, an additional copy of p53 decreases proliferation and increases ciliated cell differentiation. Using single cell RNA-Seq, we expose heterogeneity within airway epithelial progenitor cells and found that cell cycle regulators, particularly p21, are altered following p53 loss. Together, these findings reveal an essential role for p53 in regulating progenitor cell behavior, which has broad implications in understanding both stem cell and cancer biology
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| Overall design |
Examination of progenitor cell behavior in p53 knock out and wild type
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| Contributor(s) |
Farin AM, Yeckes AR, Wang Y, Selvagio AS, Gangalapudi V, Kirsch DG, Tang J, Stripp BR |
| Citation(s) |
27880895 |
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| Submission date |
Feb 17, 2016 |
| Last update date |
Oct 11, 2021 |
| Contact name |
AGCT Core |
| Organization name |
Cedars Sinai Medical Center
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| Department |
BMS
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| Street address |
8687 Melrose Ave, PDC B230
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| City |
West Hollywood |
| State/province |
CA |
| ZIP/Postal code |
90069 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (150)
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| Relations |
| BioProject |
PRJNA312408 |
| SRA |
SRP070468 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE78045_20150923_Stripp_C1_WT.all.tpm.txt.gz |
1.2 Mb |
(ftp)(http) |
TXT |
| GSE78045_20150924_Stripp_C1_p53_KO_Mouse.all.tpm.txt.gz |
1.2 Mb |
(ftp)(http) |
TXT |
| GSE78045_low_input_RNA_d30_fpkm.txt.gz |
733.0 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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