Genetic characterization of AMPK-interacting genes in germline stem cell quiescence and integrity in «Caernorhabditis elegans»
Bibliographic record
Abstract
In response to adverse conditions, C. elegans can enter an alternative developmental stage called dauer.In this state the larva undergoes several changes in order to conserve energy and withstand environmental stress.One such change occurs in the germline, where the germline stem cells (GSC) arrest their mitotic divisions and remain quiescent for the duration of this stage.Previous studies have identified the catalytic subunit of AMP-activated protein kinase (AMPK), aak--2, to be necessary in establishing this cell cycle quiescence.The aak--2 mutants exhibit pronounced germline hyperplasia compared to the normal dauer, however the molecular mechanism through which AMPK controls the GSC proliferation remains unclear.To address this question, we identified potential AMPK targets involved in the GSC quiescence by conducting a genome--wide RNAi suppressor screen for candidates that rescue the aak--2--induced hyperplasia.After screening 18,432 genes, we identified 59 candidates, which were further categorized into gene ontology groups.Of particular interest are genes necessary for miRNA--dependent gene silencing and components of the extracellular matrix (ECM), important constituents of stem cell niches.In addition we also discovered that animals exhibiting the aak--2--dependent hyperplasia in dauer are sterile and have severe morphological germline defects following the recovery from dauer.This demonstrates the importance of AMPK--dependent dauer germline quiescence on post--dauer reproduction.Candidate suppressors of the dauer germline hyperplasia failed to rescue the sterility phenotype, suggesting that although AMPK-dependent, the processes that control the GSC quiescence in dauer and the germline recovery post--dauer are independent. RésuméEn réponse à des conditions défavorables, les vers C. elegans peuvent entrer dans un état de développement alternatif appelé dauer.Dans cet état, la larve subit plusieurs changements afin d'économiser son énergie et résister aux contraintes de l'environnement.Un tel changement se produit dans la lignée germinale; les cellules souches de lignée germinale (CGC) stoppent leurs divisions mitotiques et restent au repos durant toute la durée de cette étape.Des études précédentes ont identifié la sous--unité catalytique de la protéine kinase AMP--dépendante (AMPK), aak--2, nécessaire à l'établissement de ce repos du cycle cellulaire.Les mutants aak--2 présentent une hyperplasie de la lignée germinale prononcée par rapport à un dauer normal, mais le mécanisme moléculaire par lequel l'AMPK contrôle la prolifération des CGC reste incertain.Pour répondre à cette question, nous avons identifié des cibles potentielles de l'AMPK impliquées dans la quiescence des CGC, en effectuant un crible ARNi à l'échelle du genome entier pour trouver les candidats qui reduisent l'hyperplasie induite par aak--2.Après avoir testé 18 432 gènes, nous avons identifié 59 candidats, qui ont ensuite été classés en groupe en function de leur ontologie respective.D'un intérêt particulier sont les gènes nécessaires pour l'extinction de gènes grace au mechanisme de miARN ainsi que les composants de la matrice extracellulaire (ECM), constituants importants des niches de cellules souches.En outre, nous avons également découvert que les animaux présentant une hyperplasie durant dauer dependante de aak--2 sont stériles et conservent de graves anomalies morphologiques de la lignée germinale après la reprise du development normal.Cela demontre l'importance de la quiescence de la lignee germinale,d'une maniere dependante de AMPK, pour la reproduction post--dauer.Nourrir les animaux en dauer avec des gènes candidats qui suppriment l'hyperplasie dauer de la lignée germinale a échoué à sauver le phénotype de stérilité, ce qui suggère que, bien que dependant de l'AMPK, les processus qui contrôlent la mise au repos de la CGC dans dauer et la récupération post--dauer de la lignée germinales.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".