MP75-07 SOX2, A MASTER REGULATOR OF STEMNESS, IS OVEREXPRESSED IN TESTICULAR TISSUE OF MEN WITH SERTOLI CELL ONLY SYNDROME
Bibliographic record
Abstract
You have accessJournal of UrologyInfertility: Basic Research & Pathophysiology (MP75)1 Apr 2019MP75-07 SOX2, A MASTER REGULATOR OF STEMNESS, IS OVEREXPRESSED IN TESTICULAR TISSUE OF MEN WITH SERTOLI CELL ONLY SYNDROME Russell Hayden*, Anna Mielnik, Ryan Flannigan, Peter Schlegel, and Darius Paduch Russell Hayden*Russell Hayden* More articles by this author , Anna MielnikAnna Mielnik More articles by this author , Ryan FlanniganRyan Flannigan More articles by this author , Peter SchlegelPeter Schlegel More articles by this author , and Darius PaduchDarius Paduch More articles by this author View All Author Informationhttps://doi.org/10.1097/01.JU.0000557251.15903.57AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVES: The SOX family of transcription factors play critical roles in development, stem cell maintenance, and cellular differentiation. SOX2 is one of the 4 Yamanaka factors, which also include OCT4, KLF4, and MYC, that are used to induce pluripotent stem cells. SOX2 is normally not expressed in the testis, in contrast to SOX3 which localizes to spermatogonial stem cells. However, preliminary RNA-sequencing results in our lab demonstrated expression of SOX2 in men with Sertoli Cell Only Syndrome (SCO). In this study we sought to substantiate these results with real time PCR (RT-PCR). METHODS: Testis biopsies were obtained during testicular sperm extraction for infertility. RNA-seq was performed on testis biopsies from 11 men with SCO and 10 with normal spermatogenesis using the Illumina HiSeq2000 platform. Reads were mapped using the STAR Aligner v2.5 against human genome hg38. Raw counts were normalized with Limma v3.6 using the R statistical package v3.4. RT-PCR was conducted on 3 men with SCO and 3 men with normal spermatogenesis on a LightCycler 480 (Roche). The RT2 qPCR platform was used in all experiments (Qiagen), and all assays were conducted in triplicate. Quality control was assured using melting point analysis, interplate calibrators, and negative controls. RESULTS: RNA-seq data demonstrated a 6-fold (p < 0.01) increase of SOX2 expression in men with SCO as compared to normal controls. The mean counts per million (CPM) for men with SCO was 46.5 (CI 35.2 - 57.8), whereas men with normal spermatogenesis had a CPM value of 7.8 (CI 5.9 - 9.8). RT-PCR results demonstrated a 2.7-fold (CI 1.7 - 4.1) increase in SOX2 expression of SCO compared to normal controls. CONCLUSIONS: SOX2 is over expressed in men with SCO as compared to normal controls. Although RT-PCR produced an attenuated result, the fold change in expression levels between SCO and normal men remained significant. Further study is needed to delineate how SOX2 overexpression may contribute to the pathophysiology of SCO, especially regarding its ability to suppress stem cell differentiation. Source of Funding: P50 HD076210, U1 1U01HD074542-01; Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust, the Mr. Robert S. Dow Foundation; Irena and Howard Laks Foundation. New York, NY; Vancouver, CanadaNew York, NY© 2019 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 201Issue Supplement 4April 2019Page: e1084-e1084 Advertisement Copyright & Permissions© 2019 by American Urological Association Education and Research, Inc.MetricsAuthor Information Russell Hayden* More articles by this author Anna Mielnik More articles by this author Ryan Flannigan More articles by this author Peter Schlegel More articles by this author Darius Paduch More articles by this author Expand All Advertisement PDF downloadLoading ...
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.009 | 0.001 |
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".