Characterization of Ubiquitin Carboxyl-Terminal Hydrolase L1 (UCH-L1) in the Fate Determination of Spermatogonia.
Bibliographic record
Abstract
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)
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 | 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 | 0.000 |
| 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".