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| Status |
Public on Aug 22, 2023 |
| Title |
Transcriptional profiling of Caenorhabditis elegans nematodes treated with L4440 (Empty Vector - EV) or grd-1 RNAi from L1 hatch, and collected at L3 of development. |
| Organism |
Caenorhabditis elegans |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Hedgehog morphogen GRD-1 regulates C. elegans growth and metabolism downstream of TOR complex 2. Both Hedgehog (Hh) signaling and target of rapamycin complex 2 (TORC2) are evolutionarily conserved pathways that regulate growth and metabolism. In C. elegans, loss of Hh morphogens often leads to developmental arrest, while loss of essential TORC2 component RICTOR (rict-1) causes delayed development, reduced brood, small size, increased fat, and shortened lifespan. Here we report that knockdown of Hh-related morphogen grd-1 causes developmental acceleration rather than arrest by speeding up molting transitions. Further, we show that RNAi to grd-1 not only suppresses the slow growth of rict-1 mutants, but also normalizes multiple abnormalities downstream of TORC2 including restoration of lifespan to near normal and partial rescue of low brood, small body size, and increased fat. Mechanistically, grd-1 slows growth downstream of TORC2 at least in part by increasing transcription of paraquat mediator 1 (PQM-1) target genes. Given the important role of TORC2 in governance of development, these data implicate grd-1 and pqm-1 as critical executors of organismal growth slowing in response to unfavorable growth conditions downstream of the nutrient sensor TORC2 in C. elegans.
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| Overall design |
Three independent passages of wildtype N2 animals were bleach synchronized and grown from larval stage 1 (L1) of development to larval stage 3 (L3) of development on three independently grown RNAi cultures of HT115 E. coli bacteria expressing L4440 (Empty Vector - EV Control) or grd-1 dsRNA to induce RNAi knockdown. Animals were collected via manual inspection at the L3 stage, and snap frozen for lysis, RNA extraction and downstream mRNA sequencing analysis. This experiment contains 3 control and 3 grd-1 knockdown replicates, for a total of 6 samples.
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| Contributor(s) |
Ahsan FM, Emans SW, Soukas AA |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Aug 22, 2022 |
| Last update date |
Aug 22, 2023 |
| Contact name |
Fasih Mubtasim Ahsan |
| E-mail(s) |
fahsan@g.harvard.edu
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| Organization name |
Massachusetts General Hospital
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| Department |
Center for Genomic Medicine
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| Lab |
Soukas Lab
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| Street address |
185 Cambridge Street CPZN 6500 Simches Research Building
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
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| Platforms (1) |
| GPL22765 |
Illumina HiSeq 4000 (Caenorhabditis elegans) |
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| Samples (6)
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| GSM6502652 |
N2 L3 animals, treated with EV control RNAi from hatch, Replicate 1 |
| GSM6502653 |
N2 L3 animals, treated with EV control RNAi from hatch, Replicate 2 |
| GSM6502654 |
N2 L3 animals, treated with EV control RNAi from hatch, Replicate 3 |
| GSM6502655 |
N2 L3 animals, treated with grd-1 control RNAi from hatch, Replicate 1 |
| GSM6502656 |
N2 L3 animals, treated with grd-1 control RNAi from hatch, Replicate 2 |
| GSM6502657 |
N2 L3 animals, treated with grd-1 control RNAi from hatch, Replicate 3 |
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| Relations |
| BioProject |
PRJNA872163 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE211807_N2L3_EV_grd1_knockdown_RNAsequencing_rawgenecountmatrix.csv.gz |
291.2 Kb |
(ftp)(http) |
CSV |
| GSE211807_N2L3_EV_grd1_knockdown_RNAsequencing_totalsamplemetadata.csv.gz |
674 b |
(ftp)(http) |
CSV |
| GSE211807_RAW.tar |
3.1 Mb |
(http)(custom) |
TAR (of SF) |
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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