Cell Regeneration最新文献

{"title":"Early emergence of inter-lobar heterogeneity in mouse embryonic lung.","authors":"Yun Yang, Yonggao Fu, Shiting Li, Zhiwen Liu, Mingzhu Wen, Naihe Jing, Xianfa Yang","doi":"10.1186/s13619-026-00303-y","DOIUrl":"10.1186/s13619-026-00303-y","url":null,"abstract":"<p><p>The mammalian lung is organized into anatomically distinct lobes, yet whether regional heterogeneity arises among different lobes remains poorly understood. Here, we performed comprehensive transcriptomic profiling of individual lung lobes at the pseudoglandular stage. Comparative analyses revealed that consistent inter-lobar divergence occurs primarily at the level of protein-coding genes. Notably, the left lung lobe exhibits enrichment of immune-response-associated gene expression and increased abundance of early general capillary (gCap) endothelial cells, whereas the right cranial lobe preferentially expresses genes associated with ventricular cardiac muscle morphogenesis and shows reduced gCap enrichment. Integration with publicly available datasets and experimental validation further confirmed the heterogeneous distribution of gCap cells. Together, our findings indicate that molecular and cellular inter-lobar heterogeneity emerges during embryonic development and highlight the significance of considering lobe identity in understanding pulmonary development and related congenital diseases.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"15 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liver regeneration governed by zonated PIEZO1 mechanotransduction.","authors":"Lin Xie, Chen Zhang, Yonglong Wei, Wenxiu Ning","doi":"10.1186/s13619-026-00305-w","DOIUrl":"10.1186/s13619-026-00305-w","url":null,"abstract":"<p><p>Mechanical forces are recognized as regulators of organ development, homeostasis, and regeneration, yet how physical cues are sensed in a region-specific manner within the liver remains unclear. In a Science article, Zhang and colleagues identify DPP4-positive zone 2 hepatocytes as a mechanosensory population, demonstrating that mechanical stress triggers the regenerative response through PIEZO1-mediated mechanotransduction. PIEZO1 activation in these cells induces NFATC3-dependent IGFBP2 expression, establishing a molecular link between tissue mechanics and spatially coordinated proliferation. This work provides a mechanistic explanation for why regeneration originates from the mid-lobule and introduces a druggable mechanotransduction axis that might be enhanced to accelerate liver repair.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"15 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The generation and characterization of CTRP9-Cre^ERT2 knock-in mice for targeting endothelial cell muscle and adipose tissues.","authors":"Qingye Wang, Zhangxi Fu, Haizhen Wang, Haiou Ao, Shounian Li, Jie Xu, Yaowei Meng, Qiyue Duan, Xiao Yang, Jun Wang, Yan Teng","doi":"10.1186/s13619-026-00300-1","DOIUrl":"10.1186/s13619-026-00300-1","url":null,"abstract":"<p><p>Vascular endothelial cells (ECs) exhibit significant diversity in different tissues. To elucidate the distinct physiological roles of individual EC subtypes, genetic mouse lines utilizing the Cre-loxP recombination system are crucial. However, there is still a lack of Cre mouse lines that specifically target muscle ECs. Here, through analysis of publicly available single-cell RNA sequencing datasets, C1q/tumor necrosis factor-related protein-9 (CTRP9) was identified as a highly selective marker for microvascular ECs in muscle and adipose tissues. A CTRP9-Cre^ERT2-tdTomato knock-in mouse line was then generated using CRISPR/Cas9, with tdTomato serving as a reporter for endogenous CTRP9 expression. By breeding these mice with Rosa26^LSL-EYFP reporter mice and administering tamoxifen, specific EYFP and tdTomato expression was observed in CD31⁺ ECs in the heart, skeletal muscle, tongue, and adipose tissue from postnatal to adult stages. The EYFP⁺ cells were mainly identified as microvascular ECs, rather than arterial or venous ECs. The CTRP9-Cre^ERT2 mouse model allows for precise and effective genetic manipulation of this distinct endothelial population, providing a valuable tool for investigating their roles in muscle metabolism, regeneration, and pathophysiology.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"15 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct regulation of Wnt signaling and EPZ5676 governs human UiPSM reprogramming via the CDX2/T/TBX6 core axis.","authors":"Kaipeng Wang, Xingnan Huang, Huiru Gao, Junyang Li, Tao Huang, Minjing Ke, Yu Fu, Zejie Lin, Duanqing Pei, Yue Qin","doi":"10.1186/s13619-026-00302-z","DOIUrl":"10.1186/s13619-026-00302-z","url":null,"abstract":"<p><p>An ideal in vitro system to study somitogenesis is induced presomitic mesoderm (UiPSM); the regulatory pathways of this system are not well understood. Here, integrated multi-omic and functional analyses were performed to elucidate the roles of Wnt signaling and EPZ5676 in UiPSM reprogramming. The findings showed that the Wnt/β-catenin signaling activation by CHIR is essential to induce UiPSM, which facilitates chromatin remodeling and the activation of major presomitic mesoderm (PSM) transcription factors (TFs). Conversely, EPZ5676 controls when reprogramming occurs and increases the efficiency of reprogramming by controlling chromatin dynamics without dictating cell fate. The TFs CDX2, T (Brachyury), and TBX6 were found to be a central regulatory axis whose functions were partially redundant. Mechanistically, CDX2 directly interacts with the regulatory regions of WNT3A, T, and TBX6, maintaining their chromatin accessibility and transcriptional activity and creating a positive feedback loop of Wnt/β-catenin-dependence. Moreover, the interaction between CDX2, T, and TBX6 with Wnt signaling is reciprocal to establish a stable regulatory network that preserves UiPSM identity and stemness. Taken together, this work shows that Wnt/β-catenin signaling coordinates UiPSM reprogramming and maintenance via the CDX2/T/TBX6 axis, which offers new mechanistic understanding of human mesoderm lineage specification and somatic cell reprogramming.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"15 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13500448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148807919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small-molecule cocktail 2SM promotes heart regeneration via inducing embryonic-like cardiomyocyte state.","authors":"Zihao Wang, Lixia Zheng, Xiaokai Ma, Peng Gao, Yuanyuan Chen, Chenglu Xiao, Xin Zhao, Zhenyan Xiao, Xiaojun Zhu, Zhe Zhang, Jing-Wei Xiong","doi":"10.1186/s13619-026-00301-0","DOIUrl":"10.1186/s13619-026-00301-0","url":null,"abstract":"<p><p>Adult mammalian cardiomyocytes exhibit limited regenerative capacity, which remains a major challenge for functional recovery after myocardial infarction (MI). Our previous study identified a cocktail of five small molecules (5SM) that promotes cardiomyocyte proliferation and heart regeneration; however, the complexity of this five-compound mixture poses significant barriers to clinical translation and mechanistic studies. Here, we identified a simplified dual-compound cocktail (2SM) composed of phenylephrine hydrochloride (PE) and harmine (HM), which also robustly enhanced cardiomyocyte proliferation in vitro and in vivo. Transcriptomic and metabolomic analyses indicated that 2SM treatment activated cardiomyocyte cell-cycle programs and metabolic reprogramming. PE activated a fetal program and contributed to the up-regulation of CCND1 and WEE1 by activating mTOR signaling pathway, thus enabling cardiomyocytes to enter the G1/S phase but not G2/M phase. HM inhibited DYRK1A and activated MMB and FOXM1-MuvB complex, resulting in the upregulation of G2/M phase gene expression, of which the upregulated CDC25 proteins dephosphorylate CDK1, thereby relieving the inhibitory effect of PE. Sequential treatment of PE followed by HM was essential for completion of cytokinesis. In summary, we identified that 2SM, two compounds of 5SM, reprogrammed cardiomyocytes into an embryonic-like state, and precisely coordinated cell cycle progression for promoting cardiomyocyte proliferation.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"15 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13457617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated inference of cellular compositions and gene expression programs by deconvolution.","authors":"Ze Zhang, Xu Wang, Fan Hong, Pei Yu, Shengbao Suo, Ye-Guang Chen","doi":"10.1186/s13619-026-00299-5","DOIUrl":"10.1186/s13619-026-00299-5","url":null,"abstract":"<p><p>While computational deconvolution is routinely used to estimate cell-type proportions from tissue mixtures, reconstructing cell-type-specific transcriptomes at single-sample resolution remains a fundamentally underdetermined algorithmic challenge. Consequently, accurate single-sample, gene-level inference is rarely achieved by existing tools. Here, we systematically benchmarked multiple deconvolution approaches across diverse biological contexts using both pseudo-bulk mixtures and real bulk RNA-seq datasets derived from multiple tissues. Evaluating the critical computational limitations in these models, we developed BayesPrism-DWLS, a framework that enables integrated inference of cell-type proportions and cell-type-specific expression at single-sample resolution. Applied to mouse colon bulk RNA-seq and spatial transcriptomics, BayesPrism-DWLS revealed cell-type-specific genes and pathways that were undetectable at the bulk or spot level. Therefore, this framework provides a robust, high-resolution tool for dissecting cell heterogeneity and supports mechanistic studies informed by cell-type-specific transcriptional programs using cost-effective sequencing data.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"15 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13457527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148700955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Species-specific functions of CSRP3 in satellite cell-driven muscle regeneration and relevance to porcine stem cell therapy.","authors":"Li Zhang, Wenya Li, Mingli Zhu, Hanyuhui Yang, Yilina Bai, Bing Sun, Yiming Xing","doi":"10.1186/s13619-026-00294-w","DOIUrl":"10.1186/s13619-026-00294-w","url":null,"abstract":"<p><strong>Background: </strong>Skeletal muscle function deteriorates with injury, disease, or aging. While stem cell therapies offer therapeutic potential, concerns remain regarding the safety and efficacy of transplanted cells. Satellite cells (SCs), the primary endogenous stem cells responsible for muscle repair, demonstrate safe transplantation but limited clinical effectiveness. A deeper understanding of the mechanisms regulating SC activation and differentiation is critical for improving muscle regeneration strategies.</p><p><strong>Methods: </strong>We examined the role of CSRP3 in SC-mediated muscle repair using injury models and myoblast differentiation assays. We compared its function in pigs and mice, employing genetic approaches, CSRP3 knockdown (CSRP3^KD), Csrp3-/- and overexpression (CSRP3^OE), to assess its impact on muscle regeneration. Additionally, we investigated the AKT-SERCA2 signaling axis and its downstream effects on calcium homeostasis, mitochondrial function, and myogenic differentiation.</p><p><strong>Results: </strong>CSRP3 was essential for muscle regeneration and SC differentiation in pigs but not in mice. Genetic ablation of CSRP3 (CSRP3^KD) impaired porcine SC differentiation and reduced regenerative capacity, while CSRP3 overexpression (CSRP3^OE) enhanced these processes. Mechanistically, CSRP3 deficiency disrupted AKT-SERCA2 signaling, leading to elevated intracellular Ca²⁺, mitochondrial dysfunction, and MYOG protein degradation. Pharmacological AKT activation rescued differentiation defects in CSRP3-deficient cells. Notably, Csrp3-/- mice showed normal SC differentiation and AKT-SERCA2 activity, highlighting a species-specific regulatory role for CSRP3.</p><p><strong>Conclusions: </strong>Our findings identify CSRP3 as a critical regulator of porcine muscle regeneration, with minimal impact in mice. These results suggest that strategically engineered porcine SCs, through CSRP3 modulation, could improve the effectiveness of xenotransplantation-based therapies for muscle repair.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"15 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13451472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148683625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Signaling pathways regulating cardiac regeneration.","authors":"Jianan Li, Minjie Hu, Lu Ding, Yongyu Wang","doi":"10.1186/s13619-026-00297-7","DOIUrl":"10.1186/s13619-026-00297-7","url":null,"abstract":"<p><p>Cardiac regeneration represents a pivotal frontier in addressing cardiovascular diseases, the leading global cause of mortality. This review integrates current advancements in understanding the molecular mechanisms driving cardiomyocyte proliferation and myocardial repair. Key signaling pathways-including Hippo/YAP, Wnt/β-catenin, NRG1-ErbB, MAPK, and Notch-orchestrate cardiomyocyte dedifferentiation, cell cycle re-entry, and tissue remodeling. Hippo inhibition promotes cardiomyocyte proliferation and cytoskeletal reorganization, while Wnt/β-catenin exhibits dual roles depending on developmental context and injury phase. NRG1-ErbB and MAPK/ERK pathways integrate metabolic reprogramming and paracrine signaling to enhance regeneration. Transcriptional regulators such as Meis1, GATA4, and Tbx20 modulate cell cycle dynamics, while extracellular matrix components (e.g., Agrin, FSTL1, POSTN) and growth factors (PDGF, FGF, VEGF, Ang-1) reshape the regenerative microenvironment. Despite progress, challenges persist in spatiotemporal control of proliferation, interspecies pathophysiological disparities, and therapeutic delivery precision. Emerging technologies-engineered myocardial grafts, transient modified mRNA systems (e.g., SMRTs), and hypoxia-mediated metabolic switching-highlight translational potential. Future strategies demand integration of multi-omics, biomaterials, and combinatorial interventions to bridge mechanistic insights with clinical applications.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"15 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13415425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148599746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generation of synthetic vascular organoids via orthogonal programming of human pluripotent stem cells.","authors":"Yun Zhao, Mengze Sun, Kun Zhang, Juan M Melero-Martin, Xi Wang, Kai Wang","doi":"10.1186/s13619-026-00298-6","DOIUrl":"10.1186/s13619-026-00298-6","url":null,"abstract":"<p><p>The development of functional human vasculature is essential for tissue engineering, disease modeling, and regenerative medicine. Conventional differentiation protocols of vascular lineages often exhibit lineage heterogeneity and limited control over cellular ratios. Here, we describe a protocol for generating vascular organoids (VOs) via orthogonal forward programming of hPSCs. By utilizing doxycycline-inducible activation of the transcription factors ETV2 and NKX3.1, hPSCs are rapidly directed toward endothelial and mural cell lineages, respectively. This strategy enables the assembly of VOs with precisely tunable cellular compositions within six days. When combined with fluorescent reporter lines (PECAM1-mRuby3 and ACTA2-EGFP), vascular networks can be visualized in real time without the need for tissue clearing or immunostaining. We detail procedures for stable cell line engineering, 3D organoid assembly, in vitro angiogenesis assays for drug screening, and in vivo transplantation under the mouse kidney capsule to form perfusable human vasculature. This platform provides a flexible, standardized, and scalable tool for investigating vascular biology, modeling inherited vasculopathies, and enhancing the vascularization of co-transplant tissues.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"15 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13369076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148435248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PRMT5 inhibition promotes cross-species spermatogonia expansion and suppresses differentiation.","authors":"Zhaokai Yao, Wen Wang, Kang Tang, Yuning Yang, Shaofang Ren, Yetian Weng, Linzi Ma, Dingyao Chen, Haoxu Gu, Jialin Wan, Zhaoting Liu, Yi Zheng, Chaohui Li, Fang Luo, Xiao-Yang Zhao, Yong Fan","doi":"10.1186/s13619-026-00293-x","DOIUrl":"10.1186/s13619-026-00293-x","url":null,"abstract":"<p><p>Spermatogonial stem cells (SSCs) hold great promise for treating male infertility, but their clinical translation is impeded by the lack of optimal conditions to maintain their undifferentiated state in vitro. In this study, we focused on epigenetic regulators upregulated during differentiation as potential targets. Through a small-molecule screen targeting such conserved regulators, we found that PRMT5 inhibition suppressed mouse SSC differentiation and enhanced their proliferation in a GDNF-deficient, differentiation-prone microenvironment in vitro. Using SSC transplantation assays, we confirmed that EPZ015666-treated SSCs retained their spermatogonial identity. This differentiation-inhibitory effect was reversible upon EPZ015666 withdrawal, allowing restoration of normal spermatogenesis. Notably, EPZ015666 also inhibited differentiation and promoted the proliferation of human and non-human primate spermatogonia in vitro. Mechanistically, EPZ015666 exerted this effect by inhibiting the enzymatic active site of PRMT5. These findings suggest that PRMT5 inhibition could provide a novel strategy for culturing human SSCs in vitro.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"15 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13338090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}