Characterization of Ubiquitin Carboxyl-Terminal Hydrolase L1 (UCH-L1) in the Fate Determination of Spermatogonia.
Notice bibliographique
Résumé
Spermatogenesis is a highly coordinated and complex process, which requires a fine balance between self-renewal and differentiation of Spermatogonial Stem Cells (SSCs) to support continuous sperm production. In the mammalian testis, SSCs represent a subset of undifferentiated Type A spermatogonia that are located at the basement membrane of the seminiferous tubules. The mechanisms that govern the fate decision of SSCs to maintain the stem cell identity versus to initiate differentiation remain largely unknown. Ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) is a deubiquitinating enzyme that is selectively expressed in the brain, testis and ovary. It has been implicated in neurological diseases as well as oncogenic processes. In the mouse and pig testis, UCH-L1 is first detected in gonocytes, the precursors of spermatogonia. Later on, the expression of UCH-L1 is restricted to undifferentiated spermatogonia (Asingle, Apair, Aalign) that are associated with the basement membrane of the seminiferous tubules. UCH-L1 is rapidly down-regulated in differentiating spermatogonia and completely undetectable in spermatocytes and spermatids. The objective of this study was to further characterize involvement of UCH-L1 in regulating the fate decision of spermatogonia. Expression of UCH-L1 was characterized by immunohistochemistry and RT-PCR in primary mouse SSCs derived from day 6 mouse testes and in the immortalized type A spermatogonial cell line C18-4. UCH-L1 was detected in mouse SSC clusters grown in vitro. Interestingly, we observed unequal segregation of UCH-L1 in daughter cells of undifferentiated Type A spermatogonia in vitro similar to what we reported previously in vivo. This suggests that undifferentiated spermatogonia are heterogeneous on the molecular level and that variation in the UCH-L1 level may serve as a potential means of regulating the fate decision of spermatogonia. In C18-4 cells, UCH-L1 was highly up-regulated in cells undergoing mitosis. These observations, combined with a previous report that over-expression of UCH-L1 in the mouse testis results in a block in meiosis and infertility, prompt us to hypothesize that a high level of UCH-L1 expression is associated with the maintenance of an undifferentiated status of spermatogonia and down-regulation of UCH-L1 is necessary for differentiation and entry into meiosis. The proposed role of UCH-L1in fate determination is potentially on both transcriptional and post-transcriptional levels. Future work will focus on identifying downstream targets regulated by UCH-L1 and manipulation of UCH-L1 to direct germ cell self-renewal vs. differentiation. Supported by 2RR17539-09, UCVM and CIHR Training Program in Genetics, Child Development and Health. (poster)
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».