|
|
GEO help: Mouse over screen elements for information. |
|
Status |
Public on Jan 28, 2024 |
Title |
BMI1 is required for melanocyte stem cell maintenance and hair pigmentation |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
|
Summary |
The epigenetic repressor BMI1 plays an integral role in promoting the self-renewal and proliferation of many adult stem cell populations, and also tumor types, primarily through silencing the Cdkn2a locus, which encodes the tumor suppressors p16Ink4a and p19Arf. However, in cutaneous melanoma, BMI1 drives epithelial-mesenchymal transition programs, and thus metastasis, while having little impact on proliferation or primary tumor growth. This raised questions about the requirement and role for BMI1 in melanocyte stem cell (MeSC) biology. Here, we demonstrate that murine melanocyte-specific Bmi1 deletion causes premature hair greying, which results from gradual MeSC loss. We establish that MeSC loss begins in the second hair cycle and is accompanied by melanocyte depletion. RNA-seq of MeSCs revealed that Bmi1 deletion induces transcriptional upregulation of p16Ink4a and p19Arf, mirroring the central role of BMI1 in other stem cell contexts. Additionally, the glutathione S-transferase enzymes Gsta1 and Gsta2 are downregulated by BMI1 loss, raising the possibility that MeSCs could be susceptible to oxidative stress. Accordingly, treatment with the antioxidant N-acetyl cysteine (NAC) partially rescued melanocyte expansion. Together, our data establish a critical role for BMI1 in MeSC maintenance that reflect a partial role for suppression of oxidative stress, and likely transcriptional repression of Cdkn2a.
|
|
|
Overall design |
Four replicates of melanocyte stem cells with targeted disruption of Bmi1 compared with four replicates of wild-type melanocyte stem cells .
|
|
|
Contributor(s) |
Wilson MM, Danielian P, Ferretti R, Whittaker CA, Lees JA |
Citation(s) |
37132544 |
|
Submission date |
Jan 25, 2022 |
Last update date |
Jan 29, 2024 |
Contact name |
Charles Arthur Whittaker |
E-mail(s) |
charliew@mit.edu
|
Organization name |
Koch Institute
|
Street address |
77 Mass Ave 76-189
|
City |
Cambridge |
State/province |
MA |
ZIP/Postal code |
02152 |
Country |
USA |
|
|
Platforms (1) |
GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
Samples (8)
|
|
Relations |
BioProject |
PRJNA800385 |
Supplementary file |
Size |
Download |
File type/resource |
GSE194373_mmwilson_012522_intCt.txt.gz |
523.7 Kb |
(ftp)(http) |
TXT |
GSE194373_mmwilson_012522_l2tpm.txt.gz |
1.3 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
|
|
|
|
|