Cell Death and Differentiation最新文献

{"title":"Integrin β6/Annexin A2 axis triggers autophagy to orchestrate hepatocellular carcinoma radioresistance","authors":"Ying Gao, Guangyan Wei, Hua Yu, Shuping Li, Yuhao Tang, Xin Yue, Yong Chen, Meixiao Zhan, Jian Wu","doi":"10.1038/s41418-024-01411-5","DOIUrl":"https://doi.org/10.1038/s41418-024-01411-5","url":null,"abstract":"<p>Radiotherapy (RT) is one of the main therapies for hepatocellular carcinoma (HCC), but its effectiveness has been constrained due to the resistance effect of radiation. Thus, the factors involved in radioresistance are evaluated and the underlying molecular mechanisms are also done. In this present study, we identified Integrin β6 (ITGB6) as a potential radioresistant gene through an integrative analysis of transcriptomic profiles, proteome datasets and survival using HCC cases treated with IR. We show that ITGB6 functionally contributed to radioresistance by activating autophagy through a series of in vitro and in vivo methods, such as clonogenic assays, autophagy flux (LC3B-GFP-mCherry reporter) analysis and a subcutaneous transplantation model. Mechanically, ITGB6 binds to Annexin A2 (ANXA2) and enhanced its stability by competitively antagonizing proteasome mediated ANXA2 degradation, thereby promoting autophagy and radioresistance. Notably, HCC radioresistance was significantly improved by either blocking ITGB6 or autophagy, but the combination was more effective. Importantly, ITGB6/ANXA2 axis triggered autophagic program endowed HCC cells with radioresistant activity in a radiated patient-derived xenograft (PDX) model and hydrodynamic injection in liver-specific <i>Itgb6</i>-knockout mice, further supported by clinical evidence. Together, our data revealed that ITGB6 is a radioresistant gene stabilizing the autophagy regulatory protein ANXA2, providing insights into the biological and potentially clinical significance of ITGB6/ANXA2 axis in radiotherapy planning of HCC.</p>","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":"95 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601485","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}

{"title":"hnRNPA2B1 deacetylation by SIRT6 restrains local transcription and safeguards genome stability","authors":"Feng Chen,&nbsp;Wenchao Xu,&nbsp;Ming Tang,&nbsp;Yuan Tian,&nbsp;Yuxin Shu,&nbsp;Xingkai He,&nbsp;Linmin Zhou,&nbsp;Qi Liu,&nbsp;Qian Zhu,&nbsp;Xiaopeng Lu,&nbsp;Jun Zhang,&nbsp;Wei-Guo Zhu","doi":"10.1038/s41418-024-01412-4","DOIUrl":"10.1038/s41418-024-01412-4","url":null,"abstract":"Repair of double strand breaks (DSBs) by RNA-binding proteins (RBPs) is vital for ensuring genome integrity. DSB repair is accompanied by local transcriptional repression in the vicinity of transcriptionally active genes, but the mechanism by which RBPs regulate transcriptional regulation is unclear. Here, we demonstrated that RBP hnRNPA2B1 functions as a RNA polymerase-associated factor that stabilizes the transcription complex under physiological conditions. Following a DSB, hnRNPA2B1 is released from damaged chromatin, reducing the efficiency of RNAPII complex assembly, leading to local transcriptional repression. Mechanistically, SIRT6 deacetylates hnRNPA2B1 at K113/173 residues, enforcing its rapid detachment from DSBs. This process disrupts the integrity of the RNAPII complex on active chromatin, which is a pre-requisite for transient but complete repression of local transcription. Functionally, the overexpression of an acetylation mimic stabilizes the transcription complex and facilitates the functioning of the transcription machinery. hnRNPA2B1 acetylation status was negatively correlated with SIRT6 expression, and acetylation mimic enhanced radio-sensitivity in vivo. Our findings demonstrate that hnRNPA2B1 is crucial for transcriptional repression. We have uncovered the missing link between DSB repair and transcriptional regulation in genome stability maintenance, highlighting the potential of hnRNPA2B1 as a therapeutic target.","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":"32 3","pages":"382-396"},"PeriodicalIF":13.7,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596851","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}

{"title":"Correction: STAT3 dictates β-cell apoptosis by modulating PTEN in streptozocin-induced hyperglycemia","authors":"Qinjie Weng,&nbsp;Mengting Zhao,&nbsp;Jiahuan Zheng,&nbsp;Lijun Yang,&nbsp;Zijie Xu,&nbsp;Zhikang Zhang,&nbsp;Jincheng Wang,&nbsp;Jiajia Wang,&nbsp;Bo Yang,&nbsp;Q. Richard Lu,&nbsp;Meidan Ying,&nbsp;Qiaojun He","doi":"10.1038/s41418-024-01405-3","DOIUrl":"10.1038/s41418-024-01405-3","url":null,"abstract":"","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":"32 2","pages":"369-369"},"PeriodicalIF":13.7,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41418-024-01405-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: RIPK1 prevents TRADD-driven, but TNFR1 independent, apoptosis during development","authors":"Holly Anderton,&nbsp;Esther Bandala-Sanchez,&nbsp;Daniel S. Simpson,&nbsp;James A. Rickard,&nbsp;Ashley P. Ng,&nbsp;Ladina Di Rago,&nbsp;Cathrine Hall,&nbsp;James E. Vince,&nbsp;John Silke,&nbsp;Gianmaria Liccardi,&nbsp;Rebecca Feltham","doi":"10.1038/s41418-024-01401-7","DOIUrl":"10.1038/s41418-024-01401-7","url":null,"abstract":"","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":"31 12","pages":"1776-1777"},"PeriodicalIF":13.7,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41418-024-01401-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Localized release of muscle-generated BDNF regulates the initial formation of postsynaptic apparatus at neuromuscular synapses","authors":"Jinkai Zhang,&nbsp;Hiu-Lam Rachel Kwan,&nbsp;Chi Bun Chan,&nbsp;Chi Wai Lee","doi":"10.1038/s41418-024-01404-4","DOIUrl":"10.1038/s41418-024-01404-4","url":null,"abstract":"Growing evidence indicates that brain-derived neurotrophic factor (BDNF) is produced in contracting skeletal muscles and is secreted as a myokine that plays an important role in muscle metabolism. However, the involvement of muscle-generated BDNF and the regulation of its vesicular trafficking, localization, proteolytic processing, and spatially restricted release during the development of vertebrate neuromuscular junctions (NMJs) remain largely unknown. In this study, we first reported that BDNF is spatially associated with the actin-rich core domain of podosome-like structures (PLSs) at topologically complex acetylcholine receptor (AChR) clusters in cultured Xenopus muscle cells. The release of spatially localized BDNF is tightly controlled by activity-regulated mechanisms in a calcium-dependent manner. Live-cell time-lapse imaging further showed that BDNF-containing vesicles are transported to and captured at PLSs in both aneural and synaptic AChR clusters for spatially restricted release. Functionally, BDNF knockdown or furin-mediated endoproteolytic activity inhibition significantly suppresses aneural AChR cluster formation, which in turn affects synaptic AChR clustering induced by nerve innervation or agrin-coated beads. Lastly, skeletal muscle-specific BDNF knockout (MBKO) mice exhibit structural defects in the formation of aneural AChR clusters and their subsequent recruitment to nerve-induced synaptic AChR clusters during the initial stages of NMJ development in vivo. Together, this study demonstrated the regulatory roles of PLSs in the intracellular trafficking, spatial localization, and activity-dependent release of BDNF in muscle cells and revealed the involvement of muscle-generated BDNF and its proteolytic conversion in regulating the initial formation of aneural and synaptic AChR clusters during early NMJ development in vitro and in vivo.","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":"32 3","pages":"546-560"},"PeriodicalIF":13.7,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41418-024-01404-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tufm lactylation regulates neuronal apoptosis by modulating mitophagy in traumatic brain injury","authors":"Weiji Weng,&nbsp;Zhenghui He,&nbsp;Zixuan Ma,&nbsp;Jialin Huang,&nbsp;Yuhan Han,&nbsp;Qiyuan Feng,&nbsp;Wenlan Qi,&nbsp;Yidong Peng,&nbsp;Jiangchang Wang,&nbsp;Jiacheng Gu,&nbsp;Wenye Wang,&nbsp;Yong Lin,&nbsp;Gan Jiang,&nbsp;Jiyao Jiang,&nbsp;Junfeng Feng","doi":"10.1038/s41418-024-01408-0","DOIUrl":"10.1038/s41418-024-01408-0","url":null,"abstract":"Lactates accumulation following traumatic brain injury (TBI) is detrimental. However, whether lactylation is triggered and involved in the deterioration of TBI remains unknown. Here, we first report that Tufm lactylation pathway induces neuronal apoptosis in TBI. Lactylation is found significantly increased in brain tissues from patients with TBI and mice with controlled cortical impact (CCI), and in neuronal injury cell models. Tufm, a key factor in mitophagy, is screened and identified to be mostly lactylated. Tufm is detected to be lactylated at K286 and the lactylation inhibits the interaction of Tufm and Tomm40 on mitochondria. The mitochondrial distribution of Tufm is then inhibited. Consequently, Tufm-mediated mitophagy is suppressed while mitochondria-induced neuronal apoptosis is increased. In contrast, the knockin of a lactylation-deficient TufmK286R mutant in mice rescues the mitochondrial distribution of Tufm and Tufm-mediated mitophagy, and improves functional outcome after CCI. Likewise, mild hypothermia, as a critical therapeutic method in neuroprotection, helps in downregulating Tufm lactylation, increasing Tufm-mediated mitophagy, mitigating neuronal apoptosis, and eventually ameliorating the outcome of TBI. A novel molecular mechanism in neuronal apoptosis, TBI-initiated Tufm lactylation suppressing mitophagy, is thus revealed.","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":"32 3","pages":"530-545"},"PeriodicalIF":13.7,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575099","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}

{"title":"The AKR1C1–CYP1B1–cAMP signaling axis controls tumorigenicity and ferroptosis susceptibility of extrahepatic cholangiocarcinoma","authors":"Chang Liu,&nbsp;Cheng Zhang,&nbsp;Hongkun Wu,&nbsp;Zhibin Zhao,&nbsp;Zhenhua Wang,&nbsp;Xiaomin Zhang,&nbsp;Jieli Yang,&nbsp;Wenlong Yu,&nbsp;Zhexiong Lian,&nbsp;Minghui Gao,&nbsp;Lin Zhou","doi":"10.1038/s41418-024-01407-1","DOIUrl":"10.1038/s41418-024-01407-1","url":null,"abstract":"Extrahepatic cholangiocarcinoma (ECC), a highly malignant type of cancer with increasing incidence, has a poor prognosis due to limited treatment options. Based on genomic analysis of ECC patient samples, here we report that aldo-keto reductase family 1 member C1 (AKR1C1) is highly expressed in human ECC tissues and closely associated with ECC progression and poor prognosis. Intriguingly, we show that inducible AKR1C1 knockdown triggers ECC cells to undergo ferroptosis. Mechanistically, AKR1C1 degrades the protein stability of the cytochrome P450 family member CYP1B1, a newly discovered mediator of ferroptosis, via ubiquitin-proteasomal degradation. Additionally, AKR1C1 decreases CYP1B1 mRNA level through the transcriptional factor aryl-hydrocarbon receptor (AHR). Furthermore, the AKR1C1–CYP1B1 axis modulates ferroptosis in ECC cells via the cAMP–PKA signaling pathway. Finally, in a xenograft mouse model of ECC, AKR1C1 depletion sensitizes cancer cells to ferroptosis and synergizes with ferroptosis inducers to suppress tumor growth. Therefore, the AKR1C1–CYP1B1–cAMP signaling axis is a promising therapeutic target for ECC treatment, especially in combination with ferroptosis inducers.","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":"32 3","pages":"506-520"},"PeriodicalIF":13.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41418-024-01407-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL3 confers oxaliplatin resistance through the activation of G6PD-enhanced pentose phosphate pathway in hepatocellular carcinoma","authors":"Xiaohan Jin,&nbsp;Yongrui Lv,&nbsp;Fengjie Bie,&nbsp;Jinling Duan,&nbsp;Chao Ma,&nbsp;Miaomiao Dai,&nbsp;Jiewei Chen,&nbsp;Lianghe Lu,&nbsp;Shuidan Xu,&nbsp;Jie Zhou,&nbsp;Si Li,&nbsp;Jiong Bi,&nbsp;Fengwei Wang,&nbsp;Dan Xie,&nbsp;Muyan Cai","doi":"10.1038/s41418-024-01406-2","DOIUrl":"10.1038/s41418-024-01406-2","url":null,"abstract":"Oxaliplatin-based therapeutics is a widely used treatment approach for hepatocellular carcinoma (HCC) patients; however, drug resistance poses a significant clinical challenge. Epigenetic modifications have been implicated in the development of drug resistance. In our study, employing siRNA library screening, we identified that silencing the m6A writer METTL3 significantly enhanced the sensitivity to oxaliplatin in both in vivo and in vitro HCC models. Further investigations through combined RNA-seq and non-targeted metabolomics analysis revealed that silencing METTL3 impeded the pentose phosphate pathway (PPP), leading to a reduction in NADPH and nucleotide precursors. This disruption induced DNA damage, decreased DNA synthesis, and ultimately resulted in cell cycle arrest. Mechanistically, METTL3 was found to modify E3 ligase TRIM21 near the 3’UTR with N6-methyladenosine, leading to reduced RNA stability upon recognition by YTHDF2. TRIM21, in turn, facilitated the degradation of the rate-limiting enzyme of PPP, G6PD, through the ubiquitination-proteasome pathway. Importantly, high expression of METTL3 was significantly associated with adverse prognosis and oxaliplatin resistance in HCC patients. Notably, treatment with the specific METTL3 inhibitor, STM2457, significantly improved the efficacy of oxaliplatin. These findings underscore the critical role of the METTL3/TRIM21/G6PD axis in driving oxaliplatin resistance and present a promising strategy to overcome chemoresistance in HCC.","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":"32 3","pages":"466-479"},"PeriodicalIF":13.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41418-024-01406-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142536562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apoptosis signaling is activated as a transient pulse in neurons","authors":"Keeley L. Spiess,&nbsp;Matthew J. Geden,&nbsp;Selena E. Romero,&nbsp;Emilie Hollville,&nbsp;Elizabeth S. Hammond,&nbsp;Rachel L. Patterson,&nbsp;Quintin B. Girardi,&nbsp;Mohanish Deshmukh","doi":"10.1038/s41418-024-01403-5","DOIUrl":"10.1038/s41418-024-01403-5","url":null,"abstract":"Apoptosis is a fundamental process of all mammalian cells but exactly how it is regulated in different primary cells remains less explored. In most contexts, apoptosis is engaged to eliminate cells. However, postmitotic cells such as neurons must efficiently balance the need for developmental apoptosis versus the physiological needs for their long-term survival. Neurons are capable of reversing the commitment to death even after the point of cytochrome c release. This ability of neurons to recover from an apoptotic signal suggests that activation of the apoptotic pathway in neurons could be much more transient than is currently recognized. Here, we investigated whether the apoptotic pathway in neurons is a persistent signal or a transient pulse in continuous presence of apoptotic stimulus. We have examined this at three key steps in apoptotic signaling: phosphorylation of c-Jun, induction of the BH3-only family proteins and Bax activation. Strikingly, we found all three of these events occur as transient signals following Nerve Growth Factor (NGF) deprivation-induced apoptosis in sympathetic neurons. This transient apoptosis signal would effectively allow neurons to reset and permit recovery if the apoptotic stimulus is reversed. Excitingly, we have also discovered that a neuron’s ability to recover from an apoptotic signal is dependent on expression of the anti-apoptotic Bcl-2 family protein Bcl-xL. Bcl-xL-deficient neurons lose the ability to recover from NGF deprivation even if NGF is restored. Additionally, we show that recovery from a previous exposure to NGF deprivation is protective against subsequent deprivation. Together, these results define a novel mechanism by which apoptosis is regulated in neurons where the transient pulse of the apoptotic signaling supports neuronal resilience.","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":"32 3","pages":"521-529"},"PeriodicalIF":13.7,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142490649","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}

{"title":"RIP1 inhibition protects retinal ganglion cells in glaucoma models of ocular injury","authors":"Bo Kyoung Kim,&nbsp;Tatiana Goncharov,&nbsp;Sébastien A. Archaimbault,&nbsp;Filip Roudnicky,&nbsp;Joshua D. Webster,&nbsp;Peter D. Westenskow,&nbsp;Domagoj Vucic","doi":"10.1038/s41418-024-01390-7","DOIUrl":"10.1038/s41418-024-01390-7","url":null,"abstract":"Receptor-interacting protein 1 (RIP1, RIPK1) is a critical mediator of multiple signaling pathways that promote inflammatory responses and cell death. The kinase activity of RIP1 contributes to the pathogenesis of a number of inflammatory and neurodegenerative diseases. However, the role of RIP1 in retinopathies remains unclear. This study demonstrates that RIP1 inhibition protects retinal ganglion cells (RGCs) in preclinical glaucoma models. Genetic inactivation of RIP1 improves RGC survival and preserves retinal function in the preclinical glaucoma models of optic nerve crush (ONC) and ischemia–reperfusion injury (IRI). In addition, the involvement of necroptosis in ONC and IRI glaucoma models was examined by utilizing RIP1 kinase-dead (RIP1-KD), RIP3 knockout (RIP3-KO), and MLKL knockout (MLKL-KO) mice. The number of RGCs, retinal thickness, and visual acuity were rescued in RIP1-kinase-dead (RIP1-KD) mice in both models, while wild-type (WT) mice experienced significant retinal thinning, RGC loss, and vision impairment. RIP3-KO and MLKL-KO mice showed moderate protective effects in the IRI model and limited in the ONC model. Furthermore, we confirmed that a glaucoma causative mutation in optineurin, OPTN-E50K, sensitizes cells to RIP1-mediated inflammatory cell death. RIP1 inhibition reduces RGC death and axonal degeneration following IRI in mice expressing OPTN-WT and OPTN-E50K variant mice. We demonstrate that RIP1 inactivation suppressed microglial infiltration in the RGC layer following glaucomatous damage. Finally, this study highlights that human glaucomatous retinas exhibit elevated levels of TNF and RIP3 mRNA and microglia infiltration, thus demonstrating the role of neuroinflammation in glaucoma pathogenesis. Altogether, these data indicate that RIP1 plays an important role in modulating neuroinflammation and that inhibiting RIP1 activity may provide a neuroprotective therapy for glaucoma.","PeriodicalId":9731,"journal":{"name":"Cell Death and Differentiation","volume":"32 2","pages":"353-368"},"PeriodicalIF":13.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41418-024-01390-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}