R-Spondin1 (NU-206) / Kyowa Kirin, Oruka Therapeutics - LARVOL DELTA

Chicken-derived R-spondin1, Wnt3a, Nrg1 and human FGF1 allow branched growth of chicken intestinal organoid cultures. (PubMed, Poult Sci) - "In agreement with the observed presence of goblet cells, we observed mucus secretion in the 2D cultures. This new and improved culture condition for chicken intestinal organoids allows for in vitro research that can partially replace animal testing with respect to, for instance, replacement of antibiotics, feed additives and drug development."

Journal • FGF1 • NRG1 • RSPO1 • WNT3 • WNT3A

RNF research trends and an RNF43-based prognostic model for colorectal cancer with immune microenvironment analysis. (PubMed, Discov Oncol) - "Through the STRING database, RNF43-interacting proteins were screened and intersected with CRC-related targets, identifying RNF43-mediated core CRC targets (RNF43, FZD1, FZD5, FZD8, LGR4, LGR5, RSPO1, RSPO2, RSPO3, RSPO4, and AKAP8L)...In conclusion, this study is the first to adopt a strategy combining "macro-level bibliometric insights" with "micro-level bioinformatics mining," systematically delineating the research trajectory of the RNF family and successfully constructing and validating a CRC prognostic risk model based on the RNF43 interaction network. This model may serve as an auxiliary stratification tool with potential prognostic value and may also reveal associations between the risk score and TME stromal activation and immune dysfunction, providing new insights for precise prognostic assessment and individualized treatment of CRC."

Journal • Colorectal Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • CD4 • CD8 • FZD5 • LGR4 • RNF43 • RSPO1 • RSPO2 • RSPO3

Molecular Mechanisms of Gonadal Differentiation Induced by 17β-Estradiol and Testosterone Propionate in Rana dybowskii. (PubMed, Animals (Basel)) - "Three female-biased genes (3α-hsd, Adcy3, Rspo1) and three male-biased genes (Ptgs2, Sox9, Shbg) were identified, with their expression dynamics aligned with histological progression. This study defines the optimal parameters and molecular signatures of bidirectional sex reversal in R. dybowskii. It provides a practical foundation for sex-control breeding and offers amphibian-based evidence for the conservation and plasticity of vertebrate sex determination."

Journal • PACERR • PTGS2 • RSPO1 • SOX9

Comparative evaluation of chemotherapy and CAR-T cell therapy in genetically engineered self-sustaining primary pancreatic cancer organoids. (PubMed, Pancreatology) - "This conditional transgenic approach reduces culture complexity while preserving key phenotypic and functional characteristics of PDAC organoids, providing a feasible proof-of-concept platform for exploratory evaluation of chemotherapy and immunotherapy responses."

IO biomarker • Journal • Gene Therapies • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • RSPO1 • WNT3A

Gene-transcription factor regulatory networks implicate primary cilia in the evolution of vertebrate sex determination and expand models of epigenetic regulation. (PubMed, PLoS One) - "Results implicate primary cilia as integrators of environmental signals underlying TSD, because known thermosensitive TSD components (e.g., calcium-redox, pSTAT3, Wnt/Rspo1/β-catenin, Dhh) overrepresented in our results are linked to primary cilia. TFs that evolved between species also regulate primary cilia and point to key changes in their sensory machinery that accompanied TSD-GSD transitions (e.g., calcium/ion channels or membrane transport components in Chrysemys versus structural elements and ciliogenesis in Apalone). This novel Primary Cilia Integration hypothesis expands current models of epigenetic regulation of turtle sexual development, the evolution of plasticity versus canalization, and warrants functional validation."

Journal • CTNNB1 • RSPO1

An empirically refined workflow for generating patient-derived organoids from epithelial ovarian cancer. (PubMed, Sci Rep) - "The refined workflow used a culture medium containing recombinant human R-Spondin 1 protein (250 ng/mL), Noggin, and NRG1, factors implicated in organoid maintenance and expansion...The SOBA technique increased the 10 day PDO yield by 2.75-fold relative to the surface-attached dome method (p < 0.0001). This empirically refined workflow can be adjusted for specific experimental applications; however, further validation across larger and clinically diverse EOC cohorts is required."

Journal • Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • NRG1 • RSPO1 • SPON1

Spectrum of Cytogenetic and Molecular Abnormalities in Disorders of Sex Development: A Retrospective Observational Study From Western India. (PubMed, Cureus) - "Management of DSD involves a multidisciplinary team from different specialities. The present study focuses on the cytogenetic and molecular diagnostic findings in children with atypical genitalia, which can be an efficient tool in the clinical diagnosis and management of DSD."

Journal • Observational data • Retrospective data • Pediatrics • CYP19A1 • CYP1A2 • CYP21A2 • RSPO1 • SRD5A2 • WT1

Integrative Transcriptomic and Metabolomic Analysis Reveal Mechanisms Underlying Differential Fecundity in Yangtze River Delta White Goat. (PubMed, Animals (Basel)) - "WGCNA further revealed three functional tissue axes associated with follicular development (ELOVL4, INHA, NR5A2), thyroid endocrine regulation (GRHL2, NAPRT), and uterine receptivity (RSPO1, AGTR2, PTGER3). Low-fecundity-associated modules were predominantly concentrated in follicular and thyroid tissues, whereas the high-fecundity-specific module was mainly enriched in uterine horn. These findings provide a multi-tissue molecular framework underlying differential fecundity in goats and identify candidate hub genes and metabolites that may serve as candidate biomarkers for fecundity assessment and selective breeding programs."

Journal • Metabolic Disorders • GRHL2 • NR5A2 • PTGER3 • RSPO1

Developmental reproductive impacts of gestational polystyrene nanoplastics exposure: precocious puberty and impaired ovarian reserve in female offspring. (PubMed, Food Chem Toxicol) - "Mechanistically, ovarian development dysregulations arise from suppressed FOXL2-CYP19A1 signaling and downregulated RSPO1/WNT4/β-catenin pathways, while precocious puberty is driven by earlier elevation of serum GnRH levels and hypothalamic reprogramming...Serum hormone profiling showed markedly reduced AMH/E2 and elevated LH, corroborated by transcriptional downregulation of key receptors (amh, ERα, and AR). These findings highlight a potential risk to fetal ovarian development posed by maternal nanoplastics exposure, urging the incorporation of developmental and reproductive toxicity into the comprehensive risk assessment of human exposure to micro/nano-plastics."

Journal • CYP19A1 • FOXL2 • RSPO1

History of the decline and repositioning of the H-Y antigen: From sex determination to reproductive immunology. (PubMed, J Reprod Immunol) - "Functional studies established SRY as the testis-determining factor, while ovarian differentiation emerged as an active genetic program involving WNT4, RSPO1, and FOXL2...Their significance is increasingly recognized in maternal-fetal immune interactions and pregnancy disorders, with placental biology revealing sex-dependent differences in immune regulation. In this short review, we reassess the conceptual development of the H-Y antigen and its significance in maternal-fetal immunology and the vertical transmission of infectious diseases."

Journal • Review • Infectious Disease • Transplantation • FOXL2 • RSPO1

Bioartificial Livers Developed From Gene-Edited Pig Hepatocyte Organoids Improve Amino Acid and Lipid Profiles in the Plasma of Patients With Liver Failure. (PubMed, MedComm (2020)) - "These hepatocytes were co-cultured with R-spondin1-overexpressing human umbilical vein endothelial cells (R-HUVECs) to form functionally stable liver organoids...Significantly, this research demonstrates that unlike the passive physical filtration of NAL, BAL serves as an active biological regulator of systemic metabolism. These findings provide a robust theoretical and practical foundation for the clinical translation of BAL technology, offering a promising strategy to improve outcomes for liver failure patients by modulating systemic metabolism."

Journal • Hepatology • Liver Failure • Transplantation

Targeted MSC therapy restores implantation by spatially reconstituting the RSPO1 niche via IL10-CXCL12 signaling. (PubMed, Pharmacol Res) - "Validation in patient-derived biopsies and organoids confirms the translational relevance of the IL10-CXCL12-RSPO1 regenerative axis. Collectively, these findings establish spatially targeted cell delivery as a precision pharmacotherapy, providing a mechanistic foundation for treating refractory infertility."

Journal • Infertility • Sexual Disorders • CXCL12 • CXCR4 • DPP4 • IL10 • RSPO1

Genome-wide association analyses for growth, carcass composition and meat quality traits of iberian pigs fattened in free open air. (PubMed, J Anim Sci) - "Eight QTLs were associated with loin yield, with genes like PREX2, RSPO1, and PDE4B...Genes linked to these traits included ELOVL6, associated with myristic and palmitic acids, and ADCY9 and ROBO1, associated with linoleic acid. Overall, these results provide novel genomic insights and markers that could enhance selection strategies in Iberian pig breeding programs, while highlighting the need for improved genomic tools tailored to local breeds."

Journal • ELOVL6 • PREX2 • RSPO1

Establishment of a broiler jejunal organoid model based on optimized activators or optimized two-step media and its assessment. (PubMed, Poult Sci) - "The results showed that JODM containing 50 or 100 ng/mL of R-spondin 1 and 2.5 μM of Chiron 99021 increased (P < 0.001) the budding percentage of the JOs up to about 80% and maintained their passaging and cryopreservation capabilities...Moreover, IOGM and TSM up-regulated (P < 0.001) marker genes expression of different intestinal functional cells compared with CMDM, and jejunal crypts sourced from broilers of different ages had no effect (P = 0.792) on the differentiation and budding percentage of JOs. In conclusion, the broiler JOs model established using the TSM-culture protocol developed in this study has the advantages of high differentiation, enriched budding structures and stable passaging and cryopreservation, providing a superior experimental model for studying the physiological responses of the broiler intestine to nutrients, feed additives, pathogens, drugs and their mechanisms."

Journal • RSPO1 • SPON1

Exploring the Involvement of RSPO1 Gene Variations in 46,XX DSD Patients With Mullerian Agenesis and/or Gonadal Dysgenesis-An Indian Study. (PubMed, J Obstet Gynaecol Res) - "Although no clearly pathogenic RSPO1 variants were identified, this study contributes important data on RSPO1 sequence variation in 46,XX DSD cases involving MA and GD."

Journal • Turners Syndrome • RSPO1

Mettl3 promotes reprogramming and axonogenesis of induced retinal ganglion cells. (PubMed, Stem Cell Reports) - "Integrated RNA-seq/MeRIP-seq analyses and gene function interrogations identified three m6A-modified genes (Prokr1, Rspo1, and Fmo2) as key mediators of Mettl3 effects. Collectively, our study elucidated the essential roles and molecular mechanisms of the m6A epitranscriptomic modification in neuronal fate reprogramming and axon development. These findings could aid future investigations designed to improve neuronal fate and axon regeneration outcomes for therapeutic purposes to treat neurodegenerative diseases."

Journal • CNS Disorders • FMO2 • METTL3 • RSPO1

Sox9a and amh indirectly cooperate to promote spermatogonia differentiation and gonadal development in Cyprinus carpio var. koi(koi carp). (PubMed, Anim Reprod Sci) - "Genetically, Wnt4, Rspo1, Foxl2, and cyp19a dominate female differentiation, while dmrt1, Sox9, SF-1, and amh govern male differentiation...Mechanistically, Sox9a interacted indirectly with amh to activate the AMHR-mediated signaling pathway, promoting Müllerian duct regression and testicular somatic cell proliferation. In addition, RNAi-mediated inhibition of Sox9a delayed testicular development.This study identifies amh and Sox9a as key interactive regulators of koi carp testicular development, reveals male gonadal differentiation mechanisms, and highlights amh as a promising gene target to boost female proportions and aquaculture economic benefits."

Journal • DMRT1 • FOXL2 • RSPO1 • SOX9 • TGFB1

Hyperoside as a promising multi-target candidate for neovascular age-related macular degeneration. mechanisms involving Wnt/β-catenin signaling, oxidative stress, and inflammation suppression. (PubMed, Phytomedicine) - "Collectively, the findings demonstrate that HYP ameliorates CNV in nAMD through a concerted inhibition of oxidative stress, inflammation, and angiogenesis, primarily by suppressing Wnt/β-catenin signaling, which positions HYP as a promising multi-target candidate for the development of novel nAMD therapies."

Journal • Age-related Macular Degeneration • Inflammation • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration • CCL2 • IL1B • IL6 • NQO1 • RSPO1 • SOD2 • TNFA • WNT7A

Optimization of RNP-CRISPR for high-efficiency gene editing in mouse intestinal organoids. (PubMed, Mol Cell Biochem) - "Using this optimized method, we generated APC-knockout organoids that exhibit Wnt pathway hyperactivation, demonstrated by R-spondin1-independent growth, increased nuclear β-catenin, and enhanced proliferation. Our method addresses a critical technical gap in murine organoid research, offering a scalable platform for intestinal disease modeling."

Journal • Preclinical • Developmental Disorders • Gastrointestinal Disorder • CTNNB1

In vitro plasticity between ureteric epithelial and distal nephron identity and maturity is controlled by extracellular signals. (PubMed, Dev Biol) - "Subsequent addition of RSPO1 induced patterning of distalized nephrons, including distal convoluted tubule and thick ascending limb of loop of Henle but lacking proximal segments or glomeruli...The same epithelium seeded as single cells in Matrigel formed epithelial spheroids and adopted a RET+ ureteric tip identity. This in vitro continuum between nephric duct, ureteric epithelium and distal nephron illustrates the role of the microenvironment in cellular identity."

Journal • Preclinical • RSPO1

The Contribution of Genetic Modifiers to Ovarian Cancer Risk in BRCA1 and BRCA2 Pathogenic Variant Carriers. (PubMed, Cancers (Basel)) - "The analysis identified 11 variants affecting both BRCA1 and BRCA2 carriers, most of which increase risk, including the following: IRS1, RSPO1, SYNPO2, BABAM1, MRPL34, PLEKHM1, and TIPARP...The only SNP reaching genome-wide significance (p < 5 × 10-8) was in BNC2. The article summarizes the growing number of genetic modifiers of ovarian cancer risk among BRCA1/2 carriers and highlights their potential to improve individualized risk assessment, enhance patient stratification, support personalized prevention and surveillance strategies, deepen the understanding of disease biology, and identify potential therapeutic targets."

Journal • Review • Oncology • Ovarian Cancer • Solid Tumor • BABAM1 • BARD1 • BRCA • BRCA1 • BRCA2 • BRIP1 • CASP8 • HRAS • ITGB3 • MRE11A • MTHFR • PARP2 • RAD51 • RSPO1 • TIPARP

Establishment of mouse endometrial assembloids with luminal epithelial-like structures in vitro. (PubMed, Zool Res) - "Optimization of the GLO culture was achieved by fine-tuning the concentrations of Wnt3a and R-Spondin1, while stromal viability and functionality were enhanced by supplementation with hydrocortisone, L-ascorbic acid, and ITS-X. Compared to existing mEOs, analyses confirmed that ALI-mEnAOs closely mimic in vivo endometrial architecture, lineage composition, phase-specific gene expression signatures, and dynamic hormonal response. This model offers a physiologically relevant platform for mechanistic investigation of endometrial function and embryo implantation dynamics."

Journal • Preclinical • WNT3A

Deletion of Rspo1 or Rspo3 in the mesenchyme does not affect Wolffian duct maintenance or morphogenesis. (PubMed, MicroPubl Biol) - "Wolffian duct maintenance and morphogenesis was unaffected in either Rspo1 or Rspo3 conditional knockout mice. Our results indicate that mesenchymal Rspo1 or Rspo3 is dispensable for Wolffian duct development in mice."

Journal • RSPO1 • RSPO3 • SPON1

Oral Delivery of R-spondin1-Loaded Small Extracellular Vesicles Activates WNT Signalling Pathway to Accelerate Intestinal Injury Repair and Reverse Ageing. (PubMed, J Extracell Vesicles) - "Furthermore, evRSPO1 treatment induces ISCs proliferation and reverses the intestinal senescence phenotype in aged mice. Collectively, this study establishes evRSPO1 as a potential first-in-class, orally deliverable therapeutic that overcomes biological barriers to activate ISCs, enabling efficient intestinal tissue repair and rejuvenation."

Journal • RSPO1

A novel variant p.Y250C of FZD4 influences Norrine/β-catenin signaling pathway that associates with familial exudative vitreoretinopathy (FEVR). (PubMed, Sci Rep) - "Overexpression of mutant FZD4 and NDP or activation with agonist R-Spordin 1 (RSPO1) reduced downstream signaling proteins, including phosphorylated β-catenin (p-β-catenin), and vascular endothelial growth factor (VEGF-A)...Fzd4 exhibited broad tissue expression, and it was notably present during the early developmental stages of retinal and ocular formation in mice. The novel missense mutation c.A749G in the FZD4 gene may impair the Norrin/β-catenin signaling pathway and alter subcellular localization, thereby driving FEVR pathogenesis."

Journal • Dyslipidemia • Retinal Disorders • LDLR • NDP • RSPO1