PTN from Leydig cells activates SDC2 and modulates human spermatogonial stem cell proliferation and survival via GFRA1.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39285301", "kind": "science-record", "revision": 2, "content_hash": "sha256:c7f1d1a02de33bb2d5b19cb43440837014e7f4aed172c4ccf8fc7e3d3d358bf0", "created_at": "2026-11-01T20:29:27Z", "updated_at": "2026-11-01T21:33:55Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "PTN from Leydig cells activates SDC2 and modulates human spermatogonial stem cell proliferation and survival via GFRA1.", "doi": "10.1186/s40659-024-00546-6", "pmid": "39285301", "authors": ["Xueheng Zhao", "Lvjun Liu", "Zenghui Huang", "Fang Zhu", "Huan Zhang", "Dai Zhou"], "journal": "Biological research", "year": 2024, "abstract": "BACKGROUND: Spermatogonial stem cells (SSCs) are essential for the maintenance and initiation of male spermatogenesis. Despite the advances in understanding SSC biology in mouse models, the mechanisms underlying human SSC development remain elusive.\nRESULTS: Here, we analyzed the signaling pathways involved in SSC regulation by testicular somatic cells using single-cell sequencing data (GEO datasets: GSE149512 and GSE112013) and identified that Leydig cells communicate with SSCs through pleiotrophin (PTN) and its receptor syndecan-2 (SDC2). Immunofluorescence, STRING prediction, and protein immunoprecipitation assays confirmed the interaction between PTN and SDC2 in spermatogonia, but their co-localization was observed only in approximately 50% of the cells. The knockdown of SDC2 in human SSC lines impaired cell proliferation, DNA synthesis, and the expression of PLZF, a key marker for SSC self-renewal. Transcriptome analysis revealed that SDC2 knockdown downregulated the expression of GFRA1, a crucial factor for SSC proliferation and self-renewal, and inhibited the HIF-1 signaling pathway. Exogenous PTN rescued the proliferation and GFRA1 expression in SDC2 knockdown SSC lines. In addition, we found downregulation of PTN and SDC2 as well as altered localization in non-obstructive azoospermia (NOA) patients, suggesting that downregulation of PTN and SDC2 may be associated with impaired spermatogenesis.\nCONCLUSIONS: Our results uncover a novel mechanism of human SSC regulation by the testicular microenvironment and suggest a potential therapeutic target for male infertility.", "claims": [{"id": "claim-method", "statement": "The t-test was used to assess the variances among the groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39285301", "locator": "sections[14] \"Statistical analysis\" paragraph 2", "quote": "The t-test was used to assess the variances among the groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The information produced by this research can be acquired from the author in question upon a reasonable inquiry.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39285301", "locator": "sections[29] \"notes\" paragraph 1", "quote": "The information produced by this research can be acquired from the author in question upon a reasonable inquiry."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:39285301"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11406790", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE112013", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE112013", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE112013", "version": null, "note": "The information produced by this research can be acquired from the author in question upon a reasonable inquiry.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The information produced by this research can be acquired from the author in question upon a reasonable inquiry.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3052917", "GSM3052918", "GSM3052919", "GSM3052920", "GSM3052921", "GSM3052922"], "sample_count": 6, "group_sizes": null, "group_sizes_basis": null, "platform": "16791", "taxon": "Homo sapiens", "title": "The Human Testis Cell Atlas via Single-cell RNA-seq (Healthy men scRNA-seq data set)", "resolution_checked_at": "2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE149512", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE149512", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE149512", "version": null, "note": "The information produced by this research can be acquired from the author in question upon a reasonable inquiry.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The information produced by this research can be acquired from the author in question upon a reasonable inquiry.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4504181", "GSM4504182", "GSM4504183", "GSM4504184", "GSM4504185", "GSM4504186", "GSM4504187", "GSM4504188", "GSM4504189", "GSM4504190", "GSM4504191", "GSM4504192", "GSM4504193", "GSM4504194", "GSM4504195", "GSM4504196", "GSM4504197"], "sample_count": 17, "group_sizes": null, "group_sizes_basis": null, "platform": "24676;27644", "taxon": "Homo sapiens", "title": "Single-cell analysis of developing and azoospermia human testicles reveals central role of Sertoli cells", "resolution_checked_at": "2026-11-01T18:06:43Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE112013 not downloaded", "asset:data:geo:GSE112013 licence not read", "asset:data:geo:GSE149512 not downloaded", "asset:data:geo:GSE149512 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": null, "specific": null, "label": "t-test", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The t-test was used to assess the variances among the groups."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "blocked", "tier": "R4", "blocking_axis": "method", "blocked_on": "method:not_determinable", "axes": {"method": {"tier": "R4", "expressible": false, "required_operations": [], "missing_operations": [], "basis": "The reader quoted the method the paper names (t-test), but the corpus's method extractor could not map it onto a DSL operation, so the method is published but not expressible."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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Transcriptome analysis revealed that SDC2 knockdown downre", "ar communication using data from single-cell RNA sequencing Using the Read.10X function, we imported the"], "order_basis": "paper_text_order:993", "id": "assay:4"}, {"role": "data_generation", "definition_id": "scrna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "unsupported", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["is of cellular communication using data from single-cell RNA sequencing Using the Read.10X function, we imported the", "object to analyze single-cell RNA sequence (scRNA-seq) datasets (GSE149512 and GSE112013) of norma", "nalysis of intercellular communication using scRNA-seq datasets obtained from normal adult testes i", "A) UMAP cluster analysis of human testicular scRNA-seq data showing the distribution of different t"], "order_basis": "paper_text_order:2296", "id": "assay:5"}]}