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Status |
Public on Dec 25, 2022 |
Title |
Inhibition of the ATM kinase rescues planarian regeneration after lethal radiation |
Organism |
Schmidtea mediterranea |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
As stem cells divide, they acquire mutations that can be passed on to daughter cells. To mitigate potentially deleterious outcomes, cells activate the DNA damage response (DDR) network, which governs several potential cellular outcomes following DNA damage, including repairing DNA or undergoing apoptosis. At the helm of the DDR are three PI3-like kinases including Ataxia Telangiectasia Mutated (ATM). We report here that knockdown of ATM in planarian flatworms enables stem cells to withstand lethal doses of radiation which would otherwise induce cell death. In this context, stem cells circumvent apoptosis, replicate their DNA, and recover function using homologous recombination-mediated DNA repair. Despite radiation exposure, atm knockdown animals survive long-term and regenerate new tissues. These effects occur independently of ATM’s canonical downstream effector p53. Together, our results demonstrate that in planarians, ATM regulates radiation-induced apoptosis. This acute, ATM-dependent apoptosis is a key determinant of long-term animal survival. Our results suggest that inhibition of ATM in these organisms could therefore potentially favor cell survival after radiation without obvious effects on stem cell behavior.
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Overall design |
Transcriptional profiling of X1 cells to determine the effect of atm knockdown
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Web link |
https://www.embopress.org/doi/full/10.15252/embr.202256112
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Contributor(s) |
Wang K, Shiroor DA, Adler CE |
Citation(s) |
36943023 |
NIH grant(s) |
Grant ID |
Grant title |
Affiliation |
Name |
R01 GM139933 |
Mechanisms driving stem cell responses to injury in planarians |
Cornell University |
Carolyn Elizabeth Adler |
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Submission date |
Dec 08, 2021 |
Last update date |
Mar 22, 2023 |
Contact name |
Carolyn Adler |
E-mail(s) |
cea88@cornell.edu
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Phone |
(607) 253-3608
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Organization name |
Cornell University
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Street address |
930 Campus road
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City |
ITHACA |
State/province |
NY |
ZIP/Postal code |
14853 |
Country |
USA |
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Platforms (1) |
GPL21689 |
Illumina NextSeq 500 (Schmidtea mediterranea) |
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Samples (16)
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GSM5724030 |
X1 cells, unc-KD-unirrad_rep4 |
GSM5724031 |
X1 cells, atm-KD-unirrad_rep1 |
GSM5724032 |
X1 cells, atm-KD-unirrad_rep2 |
GSM5724033 |
X1 cells, atm-KD-unirrad_rep3 |
GSM5724034 |
X1 cells, atm-KD-unirrad_rep4 |
GSM5724035 |
X1 cells, unc-KD-rad_rep1 |
GSM5724036 |
X1 cells, unc-KD-rad_rep2 |
GSM5724037 |
X1 cells, unc-KD-rad_rep3 |
GSM5724038 |
X1 cells, unc-KD-rad_rep4 |
GSM5724039 |
X1 cells, atm-KD-rad_rep1 |
GSM5724040 |
X1 cells, atm-KD-rad_rep2 |
GSM5724041 |
X1 cells, atm-KD-rad_rep3 |
GSM5724042 |
X1 cells, atm-KD-rad_rep4 |
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Relations |
BioProject |
PRJNA787217 |
SRA |
SRP349815 |
Supplementary file |
Size |
Download |
File type/resource |
GSE190454_RAW.tar |
3.3 Mb |
(http)(custom) |
TAR (of TAB) |
GSE190454_Raw_gene_counts_matrix.txt.gz |
593.1 Kb |
(ftp)(http) |
TXT |
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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