Stem cells and development最新文献

{"title":"Umbilical Cord-Derived Cell-Based Interventions for Bronchopulmonary Dysplasia and Related Complications in Preterm Infants: A Bayesian Sparse-Data Meta-Analysis.","authors":"Yonghao Wen, Yunlong Duan, Ru Nie, Siai Chen, Jingxin Yan, Manjun Deng, Haining Fan","doi":"10.1177/15473287261479169","DOIUrl":"10.1177/15473287261479169","url":null,"abstract":"<p><p>Bronchopulmonary dysplasia (BPD) is a major complication of prematurity with limited disease-modifying therapies. We evaluated umbilical cord-derived cell-based interventions for BPD and related complications in preterm infants. This Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020-based systematic review and meta-analysis were registered in PROSPERO. PubMed, Cochrane Library, Web of Science, CNKI, and Wanfang were searched from inception to June 14, 2026. Comparative clinical studies of umbilical cord-derived cell-based interventions in preterm infants at risk of or diagnosed with BPD were included. Outcomes included BPD, BPD severity, death, persistent pulmonary hypertension of the newborn (PPHN), patent ductus arteriosus (PDA), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), late-onset sepsis (LOS), and adverse events (AEs). Bayesian random-effects meta-analysis used a binomial-normal hierarchical model to estimate pooled odds ratios (ORs), 95% credible intervals (CrIs), prediction intervals, and heterogeneity. Twelve studies were included. Umbilical cord-derived cell-based interventions showed a possible protective effect on overall BPD (OR, 0.48; 95% CrI, 0.14-1.20). Stronger associations were observed for severe BPD (OR, 0.17; 95% CrI, 0.01-0.85), moderate or severe BPD (OR, 0.28; 95% CrI, 0.09-0.70), and ROP stage ≥3 (OR, 0.17; 95% CrI, 0.02-0.65). No conclusive benefit or harm was observed for death, PPHN, PDA, IVH, NEC, or LOS. No treatment-related serious AEs were identified. However, prediction intervals were generally wide, and the certainty of evidence was low to very low for most outcomes. Umbilical cord-derived cell-based interventions may reduce the risk of moderate or severe BPD in preterm infants, with an additional potential benefit for ROP stage ≥3. Current evidence remains limited, and larger randomized trials with standardized outcomes and long-term follow-up are needed.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"386-396"},"PeriodicalIF":2.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148803789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond Morphology: Reframing Lymph-Node Metastasis Prediction Through Clonal Ecology-Decades-Long Genomic Instability and Polyclonal-to-Monoclonal Transitions as the Missing Dimension in Cancer.","authors":"Keira Noelle Zhong, Katelyn S Ge, Henry Michael Lee, Shengwen Calvin Li","doi":"10.1177/15473287261475554","DOIUrl":"10.1177/15473287261475554","url":null,"abstract":"<p><p>Recent whole-genome, lineage-tracing, single-cell, and spatial studies have reshaped our understanding of tumor evolution, revealing that cancers can arise from polyclonal populations, undergo decades-long genomic instability before clinical detection, and progress through dynamic changes in subclonal composition, cellular state, and ecological organization. These findings challenge the assumption underlying morphology-based prediction models that metastatic risk can be inferred from static histological features alone. Here, we revisit lymph-node metastasis prediction in colorectal cancer through clonal ecology, integrating computational pathology with evolutionary oncology. Drawing on the subclonal switchboard model proposed in 2012 and subsequent artificial intelligence (AI)-enabled approaches for tracking dominant and dormant subclones, we synthesize evidence that metastatic potential reflects clonal ancestry, evolutionary timing, spatial niche architecture, cellular plasticity, intercellular interactions, dormancy, and treatment-driven shifts in subclonal fitness. We define five complementary methodological pillars for operationalizing clonal ecology: single-cell transcriptomics for resolving rare subclones, evolutionary trajectories, and adaptive cell states; lineage tracing and phylogenetics for reconstructing clonal ancestry and divergence; spatial transcriptomics and genomics for mapping subclonal geography and tumor-stromal-immune interactions; longitudinal liquid biopsy surveillance for monitoring residual disease, clonal turnover, and emerging resistance; and AI-enabled multimodal integration for connecting histopathology, genomics, spatial biology, and longitudinal data into predictive ecological-state models. Multiple-instance learning and pathology foundation models provide scalable computational foundations for evolution-aware prediction. Translationally, dormant subclones represent actionable reservoirs of recurrence. A longitudinal clinical and experimental study of KMT2A-rearranged acute myeloid leukemia further supports central predictions of the subclonal switchboard framework by demonstrating treatment-associated shifts in subclonal dominance, persistence of cryptic adaptive programs, and ecological rewiring during resistance and relapse. We propose clonal ecology as a measurable dimension for extending morphology-driven prediction toward integrative models that anticipate evolutionary transitions, identify therapeutic windows, and proactively constrain adaptive tumor ecosystems before resistant or metastatic subclones achieve clinical dominance.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"325-338"},"PeriodicalIF":2.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148764156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Sestrin2 on Angiogenesis of Human Umbilical Vein Endothelial Cells in Hypoxia Environment.","authors":"Rui Chen, Lina Ren, Sen Xu, Yian Guan, Xuan Zhang, Yi Li, Ping Zhou, Dongyang Ma, Liling Ren","doi":"10.1177/15473287261472709","DOIUrl":"10.1177/15473287261472709","url":null,"abstract":"<p><p>Prevascularized cell sheets are widely used in tissue engineering; however, enhancing their angiogenic potential within hypoxic microenvironments remains a significant challenge. In this study, we employed genetic manipulation to upregulate Sestrin2 (SESN2) expression in human umbilical vein endothelial cells (HUVECs) and investigated its effect on their angiogenic potential under hypoxic conditions. Transwell migration and Matrigel tube formation assays confirmed that SESN2 significantly promoted proliferation, migration, and tube formation of HUVECs under hypoxia, thereby enhancing angiogenesis. Furthermore, HUVECs overexpressing SESN2 were seeded onto cell sheets, and immunofluorescence staining for CD31 revealed increased lumen formation compared with the control group. SESN2 was also found to promote the secretion of vascular endothelial growth factor A and platelet-derived growth factor BB <i>in vitro</i>. Subsequent subcutaneous implantation studies demonstrated that prevascularized cell sheets with SESN2 overexpression enhanced angiogenesis and promoted the formation of functional blood vessels. In conclusion, SESN2 improves the vascularization capacity of tissue-engineered grafts in hypoxic environments, thereby facilitating successful transplantation of engineered tissues.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"358-370"},"PeriodicalIF":2.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148610689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of Exosome Derived from Mesenchymal Stem Cells after Cerebral Stroke: The Role of Exosomes on Mitochondrial Dysfunction.","authors":"Nasibeh Ghandy, Motahare Gholami Moghadam, Fatemeh Imanikhah, Aida Navaei Feyzabady, Mehrdad Hajinejad","doi":"10.1177/15473287261466353","DOIUrl":"10.1177/15473287261466353","url":null,"abstract":"<p><p>Stroke is a major cerebrovascular event leading to high rates of disability and mortality around the world. Fundamental research has elucidated the pathological processes of stroke to inform effective therapeutic strategies. Mitochondria, as the primary energy source for neurons, play a pivotal role in maintaining nervous tissue homeostasis, and disruptions in their function contribute to mitochondrial dysfunction, neuronal injury, and apoptosis. Exosomes, particularly those derived from mesenchymal stem cells (MSCs), exhibit remarkable potential as an ideal therapeutic modality. Owing to their nanoscale dimensions and bioactive cargo, exosomes can traverse the blood-brain barrier and modulate injury outcomes in the central nervous system (CNS). This review synthesizes prior studies to delineate the current status and therapeutic promise of MSC-derived exosomes as a cell-free approach for stroke management.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"339-347"},"PeriodicalIF":2.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148765578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of Cochlear Nucleus Synaptogenesis by Progranulin in a Stem Cell-Based Coculture Model.","authors":"Anika Tabassum, Pagadala Praveena Reddy, Oluwafemi Agboola, Meng Deng, Zhengqing Hu","doi":"10.1177/15473287261472696","DOIUrl":"10.1177/15473287261472696","url":null,"abstract":"<p><p>The cochlear nucleus (CN) is the first central relay of auditory information, receiving input from spiral ganglion neurons (SGNs) through specialized synapses whose molecular regulation remains incompletely defined. Here, we examined the role of Progranulin (<i>Grn</i>) in a stem cell-based CN synaptogenesis using an <i>in vitro</i> coculture model. DsRed-expressing mouse embryonic stem cells were differentiated into SGN-like neurons (deSGNs) and cocultured for 4 days with primary CN neurons isolated from postnatal days 3-6 wild-type (<i>Grn^+/+</i>) or <i>Grn</i>-deficient (<i>Grn^-/-</i>) mice. Cocultures containing <i>Grn^+/+</i> mouse CN neurons exhibited abundant neurite interactions and synaptic puncta between deSGNs and CN neurons. In contrast, neural connectivity and synaptic puncta were markedly reduced in cocultures with <i>Grn^-/-</i> mouse CN neurons. Supplementation with recombinant Progranulin protein significantly restored neurite connectivity and synaptic puncta formation in <i>Grn^-/-</i> mouse CN neuron cocultures. Dose-response analysis further demonstrated that Progranulin concentrations of 0.1-1 µM effectively rescued neurite connection and synaptic features to levels comparable to those observed in <i>Grn^+/+</i> mouse CN neuron cocultures. These findings identify <i>Grn</i> as a critical regulator of CN synapse formation <i>in vitro</i> and provide mechanistic insight relevant to stem cell-based strategies aimed at reconstructing SGN-CN synapses for future auditory repair.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"348-357"},"PeriodicalIF":2.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148633397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<b><i>Retraction:</i></b> Transcriptional Repression of Mad-Max Complex by Human Umbilical Cord Blood Stem Cells Downregulates Extracellular Signal-Regulated Kinase in Glioblastoma.","authors":"","doi":"10.1177/15473287261468886","DOIUrl":"https://doi.org/10.1177/15473287261468886","url":null,"abstract":"","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"15473287261468886"},"PeriodicalIF":2.0,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148665488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Survival, Illness Severity, and Time-to-Treatment Analysis in Dogs with Immune-Mediated Hemolytic Anemia Following Intravenous Allogeneic Mesenchymal Stem Cell Therapy: A Multicohort Follow-Up Study.","authors":"Steven D Garner, Emily D Laughrun, Melinda Wharton","doi":"10.1177/15473287261467226","DOIUrl":"10.1177/15473287261467226","url":null,"abstract":"<p><p>Steroid-refractory immune-mediated hemolytic anemia (IMHA) in dogs carries high early mortality, and the 15%-30% of cases that fail corticosteroid-based therapy represent a population with few effective options and a narrowing treatment window. In a prior retrospective study, intravenous allogeneic mesenchymal stem cell (MSC) therapy achieved a 76.7% hematological success rate in 43 dogs with steroid-refractory IMHA. The present multicohort follow-up study extends that work by characterizing illness severity, time-to-treatment, and long-term survival across 137 eligible patients from the same database. In Kaplan-Meier analysis of all 137 eligible patients, comprising both the nonsurvivor cohort (<i>n</i> = 57) and the lifespan registry (<i>n</i> = 80), median survival was 1,695 days (4.6 years) in the primary cohort and was not reached in the protocol-assessable cohort (<i>n</i> = 120). Estimated 1-year survival was 56.9% (95% CI: 48.2%-64.7%) and 65.0% (95% CI: 55.7%-72.8%), respectively, and the survival probability stabilized at approximately 52% through 8.1 years of follow-up. Among the 57 nonsurvivors, 51 had sufficient diagnostic data to calculate a Canine Hemolytic Anemia Objective Score (CHAOS) score; two-thirds (66.7%) met the high-risk threshold (CHAOS ≥ 3) at diagnosis. This exceeds the approximately 50% estimated from a published multicenter reference population, indicating that the Safari nonsurvivor cohort was enriched for severely ill dogs at presentation. Median post-treatment survival in nonsurvivors was 8 days (IQR: 3-38), and dogs receiving only one MSC dose had markedly shorter survival than those receiving two or more (median 4 vs. 19 days, <i>P</i> < 0.01), consistent with fulminant disease limiting completion of therapy rather than treatment failure. Diagnosis-to-treatment delay was shorter in survivors than in nonsurvivors (median 13 vs. 25 days), an exploratory finding warranting prospective evaluation. Taken together, these findings suggest that nonsurvival reflects the severity of the underlying disease and that dogs who respond to MSC therapy have potential for durable multiyear remission.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"310-318"},"PeriodicalIF":2.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148475113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ATG5 Engineers Stem Cell Plasticity to Regulate Functional Fitness During Development and Disease.","authors":"Fahika Nazeerulla, Ishani Banerjee, Manash Kumar Paul, Subhadip Mukhopadhyay","doi":"10.1177/15473287261463931","DOIUrl":"10.1177/15473287261463931","url":null,"abstract":"<p><p>Autophagy, an evolutionarily conserved and tightly controlled process in eukaryotic cells, allows them to respond to stress by selectively eliminating dysfunctional or unwanted materials to promote metabolic flexibility and maintain homeostasis. While autophagy is orchestrated by different autophagy (ATG)-related genes, whose regulation varies considerably according to tissue type and developmental stage. In this review, we investigate how regardless of the different players involved in autophagy, ATG5 emerges as a unique, highly conserved, critical molecule that acts as a central rheostat to control the stem cell fate, metabolic adaptability, and govern the immune signature pattern in cells. The journey of ATG5 modulation from physiological developmental variation to pathological scenario brings out the translational impact of ATG5. On the one hand, ATG5 promotes exit from the pluripotent state by c-Myc degradation during differentiation of specific lineages (involved in neurogenesis, adipogenesis, and hematopoiesis), while on the other hand, it has a critical involvement in metabolic circuitry via rewiring autophagy through modulation of lipophagy, mitophagy, and acetyl-CoA epigenetics. Taken together, this work summarizes new findings that centrally place ATG5 as a driver that engineers a coordinated crosstalk between the metabolic state and cell fate decisions and immune responses. These insights position ATG5 as a critical and therapeutic target for developmental disorders, cancer, and immune-metabolic diseases.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"290-309"},"PeriodicalIF":2.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148414373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Mesenchymal Stem Cell Therapy for Alzheimer's Disease: A Systematic Review and Meta-Analysis.","authors":"Yonghao Wen, Shuhao Zhan, Yunlong Duan, Mingquan Pang, Jingxin Yan, Manjun Deng, Haining Fan","doi":"10.1177/15473287261468404","DOIUrl":"10.1177/15473287261468404","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the leading cause of dementia, and effective disease-modifying therapies remain limited. Mesenchymal stem cells (MSCs) have shown therapeutic potential because of their neuroprotective and immunomodulatory properties, but clinical evidence remains inconclusive. We systematically evaluated the efficacy and safety of MSC therapy in AD. Following the PRISMA 2020 guidelines and a PROSPERO-registered protocol (CRD420261329891), we searched PubMed, the Cochrane Library, Embase, Web of Science, CNKI, and Wanfang from inception to March 1, 2026. Clinical studies of patients with primary AD treated with MSCs were included. Outcomes covered cognition, daily function, neuropsychiatric symptoms, biomarkers, imaging findings, and adverse events. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were pooled using R. Risk of bias was assessed with the RoB 2 tool, and evidence certainty was assessed with GRADE. Six studies involving 196 patients were included. Overall analyses showed no significant improvement in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) or Mini-Mental State Examination (MMSE) at 12-16 weeks or 24-26 weeks after MSC treatment versus placebo, with substantial heterogeneity. Dose-stratified analyses suggested significant benefits of low-dose MSCs on ADAS-Cog (SMD = -1.33, 95% CI: -2.35 to -0.31) and MMSE (SMD = 2.59, 95% CI: 0.52-4.66). MSC therapy significantly improved Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL; SMD = 3.27, 95% CI: 1.79-4.75), but not Neuropsychiatric Inventory (NPI) or Quality of Life in Alzheimer's Disease (QOL-AD) scale. Biomarker analyses showed no significant overall effects on Aβ42 or total tau, although subgroup analyses suggested possible increases in Aβ42 and reductions in total tau at certain doses. Imaging data from two studies indicated potential protective effects on hippocampal atrophy. MSC therapy was generally well-tolerated, although intracerebroventricular administration was associated with more transient adverse events. Evidence certainty was low to very low for most outcomes. MSC therapy for AD appears feasible and relatively safe, with potential cognitive and disease-modifying effects. However, current clinical evidence remains insufficient to confirm its efficacy.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"277-289"},"PeriodicalIF":2.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148551797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effects of Circadian Period Misalignment on Odontogenesis.","authors":"Raed Said, Helya Mortazavi, Ibrahim Hoja, David Cooper, Silvana Papagerakis, Petros Papagerakis","doi":"10.1177/15473287261466918","DOIUrl":"https://doi.org/10.1177/15473287261466918","url":null,"abstract":"<p><p>Most cellular and physiological activities are temporally organized, with many following robust circadian oscillations over the 24-h day. Mineralized dental tissues formation during odontogenesis provide an especially tractable model to study such temporal control, as they display clear daily patterns of cell behavior and matrix accretion. In this pilot study, the temporal dimension of odontogenesis was examined using two complementary circadian knockout (KO) mouse models that exhibit opposing chronotypes; Cryptochrome1 (<i>Cry1</i>) KO, characterized by a 1-h shortened circadian period, and Cryptochrome2 (<i>Cry2</i>) KO, characterized by a 1-h lengthened period. Our data revealed distinct chrono/genotype-phenotype coupling across the dental tissues examined. <i>Cry2</i> targeting resulted in more pronounced changes with significantly augmented dentin/cementum deposition accompanied by constricted pulp chambers. In enamel, targeting the <i>Cry</i> genes resulted in less noticeable effects with an accelerated early enamel matrix deposition rate observed in <i>Cry2</i> mutants, while enamel mineralization was slightly slowed down, whereas targeting <i>Cry1</i> resulted in an opposite pattern, slowed down secretion, and precocious enamel mineralization. Collectively, our results strongly suggest that there is a correlation between circadian period length and dental matrix proteins deposition, whereby longer periods favor elevated secretion rates while shorter periods result in a slightly reduced output. On the other hand, no similar effects were noted in mineral content, as mature enamel, bone, and dentin mineral densities did not differ significantly across the two KO models. Overall, this work identifies the cryptochrome 2 gene as a potent regulator of dentinogenesis and mandibular bone remodeling with a limited impact on amelogenesis. It also highlights intrinsic biological time as a fundamental axis along which the architecture of mineralized craniofacial tissues is patterned.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"15473287261466918"},"PeriodicalIF":2.0,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148427746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}