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Three-way regulation of transcription 转录的三向调控
IF 21.3 1区 生物学
Nature Cell Biology Pub Date : 2025-05-15 DOI: 10.1038/s41556-025-01675-0
Sabrya Carim
{"title":"Three-way regulation of transcription","authors":"Sabrya Carim","doi":"10.1038/s41556-025-01675-0","DOIUrl":"https://doi.org/10.1038/s41556-025-01675-0","url":null,"abstract":"<p>Phosphorylation regulates the transition between phases of the RNA polymerase II (RNAPII) transcription cycle. The elongation factor SPT5 is phosphorylated by the CDK9 kinase on a flexible linker and in C-terminal repeat 1 (CTR1) to regulate promoter-proximal pausing and termination. In this study, Sun and Fisher report that the C-terminal repeat 2 (CTR2) region in SPT5 is also phosphorylated by CDK9, and this modification regulates the transcription elongation rate. The researchers investigated the effect of mutating CTR1 or CTR2 in a human colon cancer cell line and found that phosphorylated CTR1 and CTR2 exert opposing effects on elongation — CTR1 accelerates elongation after pause release, whereas CTR2 acts as a brake on RNAPII elongation rate. Despite opposing functions on RNAPII elongation, phosphorylation of CTR1 and CTR2 reinforced gene expression.</p><p>This study shows that three-way phosphorylation of SPT5 by CDK9 collectively regulates RNAPII pausing and elongation rate for productive transcription.</p>","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"32 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Stem cells against Parkinson’s 干细胞对抗帕金森症
IF 21.3 1区 生物学
Nature Cell Biology Pub Date : 2025-05-15 DOI: 10.1038/s41556-025-01676-z
Stylianos Lefkopoulos
{"title":"Stem cells against Parkinson’s","authors":"Stylianos Lefkopoulos","doi":"10.1038/s41556-025-01676-z","DOIUrl":"https://doi.org/10.1038/s41556-025-01676-z","url":null,"abstract":"<p>Previous studies have developed an approach to derive midbrain dopaminergic neurons from human embryonic stem (hES) cells. Tabar et al. now use these cells in an open, phase 1 clinical trial aiming to treat Parkinson’s disease (PD).</p><p>The authors primarily assessed the safety and tolerability of bilateral grafts of cryopreserved dopaminergic neuron progenitor cells into the putamen of individuals with PD. Twelve patients were enrolled into two cohorts — five patients were subjected to low-dose treatment (0.9 × 10<sup>6</sup> cells per putamen) and seven patients were subjected to high-dose treatment (2.7 × 10<sup>6</sup> cells per putamen). Both cohorts underwent immunosuppression for a year. After 12 months, no major adverse events related to the transplant or immunosuppression were detected. Further studies showed that the transplanted dopaminergic neurons survived up to 18 months after transplantation. In addition, the high-dose cohort patients displayed an improvement in their PD symptoms.</p>","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"47 43 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Stem cells in the clinic 干细胞在临床中的应用
IF 21.3 1区 生物学
Nature Cell Biology Pub Date : 2025-05-15 DOI: 10.1038/s41556-025-01677-y
Stylianos Lefkopoulos
{"title":"Stem cells in the clinic","authors":"Stylianos Lefkopoulos","doi":"10.1038/s41556-025-01677-y","DOIUrl":"https://doi.org/10.1038/s41556-025-01677-y","url":null,"abstract":"<p>Treatments that aim to alleviate the symptoms of Parkinson’s disease (PD) are only effective at the early stages and eventually lead to complications. Sawamoto et al. conduct an open-label, phase 1/2 clinical trial to test induced pluripotent stem (iPS) cell-derived dopaminergic cells as a therapeutic approach for PD.</p><p>The researchers bilaterally transplanted allogeneic iPS cell-derived dopaminergic progenitors into seven patients with PD, in which three received a low-dose treatment (2.1 –2.6 × 10<sup>6</sup> cells per hemisphere), four received high-dose treatment (5.3–5.5 × 10<sup>6</sup> cells per hemisphere), and all patients received tacrolimus as an immunosuppressant. No serious adverse events were detected, and MRI imaging revealed a gradual increase in the graft volume over 24 months, with no tumour-like features. Although the major purpose of the trial was to assess safety, Sawamoto et al. also reported some overall symptom improvements, thus providing data on the potential efficacy of the approach.</p>","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"43 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
ALDH4A1 functions as an active component of the MPC complex maintaining mitochondrial pyruvate import for TCA cycle entry and tumour suppression ALDH4A1作为MPC复合物的活性成分，维持线粒体丙酮酸的输入，用于TCA循环进入和肿瘤抑制
IF 21.3 1区 生物学
Nature Cell Biology Pub Date : 2025-05-12 DOI: 10.1038/s41556-025-01651-8
Che-Chia Hsu, Chi-Yun Wang, Rajesh Kumar Manne, Zhen Cai, Vasudevarao Penugurti, Rajni Kant, Ling Bai, Bo-Syong Pan, Tingjin Chen, Yuan-Ru Chen, Hsin-En Wu, Yan Jin, Haiwei Gu, Chia-Yang Li, Hui-Kuan Lin
{"title":"ALDH4A1 functions as an active component of the MPC complex maintaining mitochondrial pyruvate import for TCA cycle entry and tumour suppression","authors":"Che-Chia Hsu, Chi-Yun Wang, Rajesh Kumar Manne, Zhen Cai, Vasudevarao Penugurti, Rajni Kant, Ling Bai, Bo-Syong Pan, Tingjin Chen, Yuan-Ru Chen, Hsin-En Wu, Yan Jin, Haiwei Gu, Chia-Yang Li, Hui-Kuan Lin","doi":"10.1038/s41556-025-01651-8","DOIUrl":"https://doi.org/10.1038/s41556-025-01651-8","url":null,"abstract":"<p>MPC1 and MPC2 are two well-known components of the mitochondrial pyruvate carrier (MPC) complex maintaining MPC activity to transport pyruvate into mitochondria for tricarboxylic acid (TCA) cycle entry in mammalian cells. It is currently unknown whether there is an additional MPC component crucially maintaining MPC complex activity for pyruvate mitochondrial import. Here we show that ALDH4A1, a proline-metabolizing enzyme localized in mitochondria, serves as a previously unrecognized MPC component maintaining pyruvate mitochondrial import and the TCA cycle independently of its enzymatic activity. Loss of ALDH4A1 in mammalian cells impairs pyruvate entry to mitochondria, resulting in defective TCA cycle entry. ALDH4A1 forms an active trimeric complex with MPC1–MPC2 to maintain the integrity and oligomerization of MPC1–MPC2 and facilitates pyruvate transport in an in vitro system. ALDH4A1 displays tumour suppression by maintaining MPC complex activity. Our study identifies ALDH4A1 as an essential component of MPC for pyruvate mitochondrial import, TCA cycle entry and tumour suppression.</p>","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"20 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143933220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Import mechanism of peroxisomal proteins with an N-terminal signal sequence 具有n端信号序列的过氧化物酶体蛋白的进口机制
IF 21.3 1区 生物学
Nature Cell Biology Pub Date : 2025-05-09 DOI: 10.1038/s41556-025-01662-5
Michael L. Skowyra, Tom A. Rapoport
{"title":"Import mechanism of peroxisomal proteins with an N-terminal signal sequence","authors":"Michael L. Skowyra, Tom A. Rapoport","doi":"10.1038/s41556-025-01662-5","DOIUrl":"https://doi.org/10.1038/s41556-025-01662-5","url":null,"abstract":"<p>Most proteins imported into peroxisomes use a carboxy-terminal PTS1 signal, which is recognized by soluble receptors that transport the cargo through a nuclear pore-like conduit in the peroxisomal membrane formed by the tyrosine and glycine-rich YG domain of PEX13. The receptors then return to the cytosol through a separate retrotranslocon. Some peroxisomal proteins instead use an amino-terminal PTS2 signal that is recognized by an adaptor called PEX7, but how they are imported is poorly understood. Here we show that PTS2 cargo is moved through the YG phase by PEX7 bound to a receptor. After cargo release inside peroxisomes, PEX7 returns to the cytosol by moving back on its own through the YG phase. The chaperone PEX39 then extracts PEX7 from the phase on the cytosolic side and helps to reload PEX7 with a new receptor and cargo to start another import cycle. Our results provide a comprehensive model of PTS2 protein import.</p>","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"120 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Regulation of RIG-I activity by phase separation reveals new therapeutic opportunities 通过相分离调节RIG-I活性揭示了新的治疗机会
IF 21.3 1区 生物学
Nature Cell Biology Pub Date : 2025-05-09 DOI: 10.1038/s41556-025-01656-3
{"title":"Regulation of RIG-I activity by phase separation reveals new therapeutic opportunities","authors":"","doi":"10.1038/s41556-025-01656-3","DOIUrl":"https://doi.org/10.1038/s41556-025-01656-3","url":null,"abstract":"After virus infection, RIG-I forms disulfide-linked oligomers that are resistant to degradation and able to enter liquid-like condensates, which is necessary for RIG-I-mediated stimulation of type I interferon signalling. RIG-I agonists and antagonists that enhance or prevent formation of disulfide-linked RIG-I oligomers, respectively, confirm that this mechanism is crucial for RIG-I function and could be harnessed to boost antiviral immunity or suppress autoimmunity caused by hyperactive RIG-I.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"2 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeting redox-sensitive MBD2–NuRD condensate in cancer cells 靶向肿瘤细胞中氧化还原敏感的MBD2-NuRD凝聚物
IF 21.3 1区 生物学
Nature Cell Biology Pub Date : 2025-04-30 DOI: 10.1038/s41556-025-01657-2
Heyang Wei, Hongdan Zheng, Siqing Wang, Yun Yang, Ruiqian Zhao, Aihong Gu, Ronggui Hu, Fei Lan, Wenyu Wen
{"title":"Targeting redox-sensitive MBD2–NuRD condensate in cancer cells","authors":"Heyang Wei, Hongdan Zheng, Siqing Wang, Yun Yang, Ruiqian Zhao, Aihong Gu, Ronggui Hu, Fei Lan, Wenyu Wen","doi":"10.1038/s41556-025-01657-2","DOIUrl":"https://doi.org/10.1038/s41556-025-01657-2","url":null,"abstract":"<p>Transcriptional silencing of hypermethylated tumour suppressor genes is a hallmark of tumorigenesis but the underlying mechanism remains enigmatic. Here we show that methyl-CpG-binding domain protein 2 (MBD2) forms nuclear condensate in diverse cancer cells, where it assembles and navigates the chromatin remodeller NuRD complex to these gene loci for transcriptional suppression, thus fuelling tumour growth. Disturbance of MBD2 condensate reduces the level of NuRD complex-specific proteins, destabilizes heterochromatin foci, facilitates chromatin relaxation and consequently impedes tumour progression. We demonstrate that MBD2 condensate is redox sensitive, mediated by C359. Pro-oxidative interventions disperse MBD2–NuRD condensate, thereby alleviating the transcriptional repression of tumour suppressor genes. Our findings illuminate a hitherto unappreciated function of MBD2 condensate in sustaining a repressive chromatin state essential for cancer cell proliferation and suggest an oxidative stress targeting approach for malignancies with excessive MBD2 condensate.</p>","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"44 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143890263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
α-Ketoglutarate promotes trophectoderm induction and maturation from naive human embryonic stem cells α-酮戊二酸促进幼年人胚胎干细胞的滋养外胚层诱导和成熟
IF 21.3 1区 生物学
Nature Cell Biology Pub Date : 2025-04-23 DOI: 10.1038/s41556-025-01658-1
Karlien Van Nerum, Anne Wenzel, Lidia Argemi-Muntadas, Eleni Kafkia, Antar Drews, Ida Sophie Brun, Viktoria Lavro, Annina Roelofsen, Nikolaos Stamidis, Sandra Bages Arnal, Cheng Zhao, Simone di Sanzo, Moritz Völker-Albert, Sophie Petropoulos, Thomas Moritz, Jan Jakub Żylicz
{"title":"α-Ketoglutarate promotes trophectoderm induction and maturation from naive human embryonic stem cells","authors":"Karlien Van Nerum, Anne Wenzel, Lidia Argemi-Muntadas, Eleni Kafkia, Antar Drews, Ida Sophie Brun, Viktoria Lavro, Annina Roelofsen, Nikolaos Stamidis, Sandra Bages Arnal, Cheng Zhao, Simone di Sanzo, Moritz Völker-Albert, Sophie Petropoulos, Thomas Moritz, Jan Jakub Żylicz","doi":"10.1038/s41556-025-01658-1","DOIUrl":"https://doi.org/10.1038/s41556-025-01658-1","url":null,"abstract":"<p>Development and lineage choice are driven by interconnected transcriptional, epigenetic and metabolic changes. Specific metabolites, such as α-ketoglutarate (αKG), function as signalling molecules affecting the activity of chromatin-modifying enzymes. However, how metabolism coordinates cell-state changes, especially in human pre-implantation development, remains unclear. Here we uncover that inducing naive human embryonic stem cells towards the trophectoderm lineage results in considerable metabolic rewiring, characterized by αKG accumulation. Elevated αKG levels potentiate the capacity of naive embryonic stem cells to specify towards the trophectoderm lineage. Moreover, increased αKG levels promote blastoid polarization and trophectoderm maturation. αKG supplementation does not affect global histone methylation levels; rather, it decreases acetyl-CoA availability, reduces histone acetyltransferase activity and weakens the pluripotency network. We propose that metabolism functions as a positive feedback loop aiding in trophectoderm fate induction and maturation, highlighting that global metabolic rewiring can promote specificity in cell fate decisions through intricate regulation of signalling and chromatin.</p>","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"17 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effects of embryonic origin, tissue cues and pathological signals on fibroblast diversity in humans 胚胎来源、组织线索和病理信号对人类成纤维细胞多样性的影响
IF 21.3 1区 生物学
Nature Cell Biology Pub Date : 2025-04-22 DOI: 10.1038/s41556-025-01638-5
Marta Torregrossa, Lindsay Davies, Machens Hans-Günther, Jan C. Simon, Sandra Franz, Yuval Rinkevich
{"title":"Effects of embryonic origin, tissue cues and pathological signals on fibroblast diversity in humans","authors":"Marta Torregrossa, Lindsay Davies, Machens Hans-Günther, Jan C. Simon, Sandra Franz, Yuval Rinkevich","doi":"10.1038/s41556-025-01638-5","DOIUrl":"https://doi.org/10.1038/s41556-025-01638-5","url":null,"abstract":"<p>Fibroblasts, once perceived as a uniform cell type, are now recognized as a mosaic of distinct populations with specialized roles in tissue homeostasis and pathology. Here we provide a global overview of the expanding compendium of fibroblast cell types and states, their diverse lineage origins and multifaceted functions across various human organs. By integrating insights from developmental biology, lineage tracing and single-cell technologies, we highlight the complex nature of fibroblasts. We delve into their origination from embryonic mesenchyme and tissue-resident populations, elucidating lineage-specific behaviours in response to physiological cues. Furthermore, we highlight the pivotal role of fibroblasts in orchestrating tissue repair, connective tissue remodelling and immune modulation across diverse pathologies. This knowledge is essential to develop novel fibroblast-targeted therapies to restore steady-state fibroblast function and advance regenerative medicine strategies across multiple diseases.</p>","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"47 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143857564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Metastatic medulloblastoma remodels the local leptomeningeal microenvironment to promote further metastatic colonization and growth 转移性髓母细胞瘤重塑局部脑膜微环境，促进进一步转移定植和生长
IF 21.3 1区 生物学
Nature Cell Biology Pub Date : 2025-04-22 DOI: 10.1038/s41556-025-01660-7
Namal Abeysundara, Alexandra Rasnitsyn, Vernon Fong, Alexander Bahcheli, Randy Van Ommeren, Kyle Juraschka, Maria Vladoiu, Winnie Ong, Bryn Livingston, Pasqualino de Antonellis, Michelle Ly, Borja López Holgado, Olga Sirbu, Shahrzad Bahrampour, Hyun-Kee Min, Jerry Fan, Carolina Nor, Abhirami Visvanathan, Jiao Zhang, Hao Wang, Lei Qin, Ning Huang, Jonelle Pallotta, Tajana Douglas, Esta Mak, Haipeng Su, Karen Ng, Kevin Yang Zhang, Craig Daniels, Calixto-Hope G. Lucas, Charles G. Eberhart, Hailong Liu, Tao Jiang, Faiyaz Notta, Vijay Ramaswamy, Jüri Reimand, Marco Gallo, Jeremy N. Rich, Xiaochong Wu, Xi Huang, Michael D. Taylor
{"title":"Metastatic medulloblastoma remodels the local leptomeningeal microenvironment to promote further metastatic colonization and growth","authors":"Namal Abeysundara, Alexandra Rasnitsyn, Vernon Fong, Alexander Bahcheli, Randy Van Ommeren, Kyle Juraschka, Maria Vladoiu, Winnie Ong, Bryn Livingston, Pasqualino de Antonellis, Michelle Ly, Borja López Holgado, Olga Sirbu, Shahrzad Bahrampour, Hyun-Kee Min, Jerry Fan, Carolina Nor, Abhirami Visvanathan, Jiao Zhang, Hao Wang, Lei Qin, Ning Huang, Jonelle Pallotta, Tajana Douglas, Esta Mak, Haipeng Su, Karen Ng, Kevin Yang Zhang, Craig Daniels, Calixto-Hope G. Lucas, Charles G. Eberhart, Hailong Liu, Tao Jiang, Faiyaz Notta, Vijay Ramaswamy, Jüri Reimand, Marco Gallo, Jeremy N. Rich, Xiaochong Wu, Xi Huang, Michael D. Taylor","doi":"10.1038/s41556-025-01660-7","DOIUrl":"https://doi.org/10.1038/s41556-025-01660-7","url":null,"abstract":"<p>Leptomeningeal metastases are the major source of morbidity and mortality for patients with medulloblastoma. The biology of the leptomeningeal metastases and the local tumour microenvironment are poorly characterized. Here we show that metastasis-associated meningeal fibroblasts (MB-MAFs) are transcriptionally distinct and signal extensively to tumour cells and the tumour microenvironment. Metastatic cells secrete platelet-derived growth factor (PDGF) ligands into the local microenvironment to chemotactically recruit meningeal fibroblasts. Meningeal fibroblasts are reprogrammed to become MB-MAFs, expressing distinct transcriptomes and secretomes, including bone morphogenetic proteins. Active bone morphogenetic protein signalling and co-implantation of tumour cells with MB-MAFs enhances the colonization of the leptomeninges by medulloblastoma cells and promotes the growth of established metastases. Furthermore, treatment of patient-derived xenograft mice with a PDGF-receptor-α neutralizing antibody enhances overall survival in vivo. Collectively, our results define a targetable intercellular communication cascade in the metastatic niche to treat leptomeningeal disease.</p>","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"31 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143857206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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