Protein & Cell最新文献_第6页

SMAD2/3-SMYD2 and developmental transcription factors cooperate with cell cycle inhibitors to guide tissue formation. SMAD2/3-SMYD2 和发育转录因子与细胞周期抑制剂合作，引导组织形成。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2024-05-17 DOI: 10.1093/procel/pwae031

Stefania Militi, R. Nibhani, Martin Pook, S. Pauklin

{"title":"SMAD2/3-SMYD2 and developmental transcription factors cooperate with cell cycle inhibitors to guide tissue formation.","authors":"Stefania Militi, R. Nibhani, Martin Pook, S. Pauklin","doi":"10.1093/procel/pwae031","DOIUrl":"https://doi.org/10.1093/procel/pwae031","url":null,"abstract":"Tissue formation and organ homeostasis is achieved by precise coordination of proliferation and differentiation of stem cells and progenitors. While deregulation of these processes can result in degenerative disease or cancer, their molecular interplays remain unclear. Here we show that the switch of human pluripotent stem cell (hPSC) self-renewal to differentiation is associated with the induction of distinct cyclin dependent kinase inhibitors (CDKIs). In hPSCs, Activin/Nodal/TGFβ signalling maintains CDKIs in a poised state via SMAD2/3-NANOG-OCT4-EZH2-SNON transcriptional complex. Upon gradual differentiation, CDKIs are induced by successive transcriptional complexes between SMAD2/3-SMYD2 and developmental regulators such as EOMES, thereby lengthening the G1 phase. This, in turn, induces SMAD2/3 transcriptional activity by blocking its linker phosphorylation. Such SMAD2/3-CDKI positive feedback loops drive the exit from pluripotency and stepwise cell fate specification that could be harnessed for producing cells for therapeutic applications. Our study uncovers fundamental mechanisms how cell fate specification is interconnected to cell cycle dynamics and provides insight to autonomous circuitries governing tissue self-formation.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":null,"pages":null},"PeriodicalIF":21.1,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140963080","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

IL-24 promotes atopic dermatitis-like inflammation through driving MRSA-induced allergic responses. IL-24 通过驱动 MRSA 诱导的过敏反应，促进特应性皮炎样炎症。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2024-05-16 DOI: 10.1093/procel/pwae030

Xinmin Qian, Meiyi Tong, Tianqing Zhang, Qingqing Li, Meng Hua, Nan Zhou, Wenwen Zeng

引用次数: 0

Alzheimer's disease: insights into pathology, molecular mechanisms, and therapy. 阿尔茨海默病：对病理学、分子机制和治疗的见解。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2024-05-11 DOI: 10.1093/procel/pwae026

Qiuyang Zheng, Xin Wang

引用次数: 0

Noncoding RNA Terc-53 and hyaluronan receptor Hmmr regulate ageing in mice. 非编码 RNA Terc-53 和透明质酸受体 Hmmr 可调节小鼠的衰老。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2024-05-09 DOI: 10.1093/procel/pwae023

Sipeng Wu, Yiqi Cai, Lixiao Zhang, Xiang Li, Xu Liu, Guangkeng Zhou, Hongdi Luo, Renjian Li, Yujia Huo, Zhirong Zhang, Siyi Chen, Jinliang Huang, Jiahao Shi, Shanwei Ding, Zhe Sun, Zizhuo Zhou, Pengcheng Wang, Geng Wang

{"title":"Noncoding RNA Terc-53 and hyaluronan receptor Hmmr regulate ageing in mice.","authors":"Sipeng Wu, Yiqi Cai, Lixiao Zhang, Xiang Li, Xu Liu, Guangkeng Zhou, Hongdi Luo, Renjian Li, Yujia Huo, Zhirong Zhang, Siyi Chen, Jinliang Huang, Jiahao Shi, Shanwei Ding, Zhe Sun, Zizhuo Zhou, Pengcheng Wang, Geng Wang","doi":"10.1093/procel/pwae023","DOIUrl":"https://doi.org/10.1093/procel/pwae023","url":null,"abstract":"One of the basic questions in the ageing field is whether there is fundamental difference between the ageing of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-ageing Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at early age was observed, indicating its involvement in normal ageing of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal ageing. AAV-delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan (Stern 2017). These findings demonstrate the complexity of ageing in mammals, and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":null,"pages":null},"PeriodicalIF":21.1,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892318","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

Exploring unconventional attributes of red blood cells and their potential applications in biomedicine. 探索红细胞的非传统属性及其在生物医学中的潜在应用。

IF 13.6 1区生物学

Protein & Cell Pub Date : 2024-05-07 DOI: 10.1093/procel/pwae001

Alkmini T Anastasiadi, Vasiliki-Zoi Arvaniti, Krystalyn E Hudson, Anastasios G Kriebardis, Constantinos Stathopoulos, Angelo D'Alessandro, Steven L Spitalnik, Vassilis L Tzounakas

引用次数: 0

Applications of genetic code expansion technology in eukaryotes. 遗传密码扩展技术在真核生物中的应用。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2024-05-07 DOI: 10.1093/procel/pwad051

Qiao-Ru Guo, Yu J Cao

引用次数: 0

Aging hallmarks of the primate ovary revealed by spatiotemporal transcriptomics. 时空转录组学揭示灵长类卵巢衰老特征

IF 21.1 1区生物学

Protein & Cell Pub Date : 2024-05-07 DOI: 10.1093/procel/pwad063

Huifen Lu, Ying Jing, Chen Zhang, Shuai Ma, Weiqi Zhang, Daoyuan Huang, Bin Zhang, Yuesheng Zuo, Yingying Qin, Guang-Hui Liu, Yang Yu, Jing Qu, Si Wang

{"title":"Aging hallmarks of the primate ovary revealed by spatiotemporal transcriptomics.","authors":"Huifen Lu, Ying Jing, Chen Zhang, Shuai Ma, Weiqi Zhang, Daoyuan Huang, Bin Zhang, Yuesheng Zuo, Yingying Qin, Guang-Hui Liu, Yang Yu, Jing Qu, Si Wang","doi":"10.1093/procel/pwad063","DOIUrl":"10.1093/procel/pwad063","url":null,"abstract":"The ovary is indispensable for female reproduction, and its age-dependent functional decline is the primary cause of infertility. However, the molecular basis of ovarian aging in higher vertebrates remains poorly understood. Herein, we apply spatiotemporal transcriptomics to benchmark architecture organization as well as cellular and molecular determinants in young primate ovaries and compare these to aged primate ovaries. From a global view, somatic cells within the non-follicle region undergo more pronounced transcriptional fluctuation relative to those in the follicle region, likely constituting a hostile microenvironment that facilitates ovarian aging. Further, we uncovered that inflammation, the senescent-associated secretory phenotype, senescence, and fibrosis are the likely primary contributors to ovarian aging (PCOA). Of note, we identified spatial co-localization between a PCOA-featured spot and an unappreciated MT2 (Metallothionein 2) highly expressing spot (MT2high) characterized by high levels of inflammation, potentially serving as an aging hotspot in the primate ovary. Moreover, with advanced age, a subpopulation of MT2high accumulates, likely disseminating and amplifying the senescent signal outward. Our study establishes the first primate spatiotemporal transcriptomic atlas, advancing our understanding of mechanistic determinants underpinning primate ovarian aging and unraveling potential biomarkers and therapeutic targets for aging and age-associated human ovarian disorders.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":null,"pages":null},"PeriodicalIF":21.1,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11075111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138831229","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}

引用次数: 0

Correction to: Modeling CADASIL vascular pathologies with patient-derived induced pluripotent stem cells. 更正：用源自患者的诱导多能干细胞模拟 CADASIL 血管病变。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2024-05-07 DOI: 10.1093/procel/pwad059

引用次数: 0

Degeneration Directory: a multi-omics web resource for degenerative diseases. 变性目录：退化性疾病的多组学网络资源。

IF 13.6 1区生物学

Protein & Cell Pub Date : 2024-05-07 DOI: 10.1093/procel/pwad066

Haoteng Yan, Changfa Lu, Chenyang Lan, Si Wang, Weiqi Zhang, Zan He, Jinghao Hu, Jiaqi Ai, Guang-Hui Liu, Shuai Ma, Yuanchun Zhou, Jing Qu

引用次数: 0

Dissecting caspase-2-mediated cell death: from intrinsic PIDDosome activation to chemical modulation. 剖析caspase-2介导的细胞死亡：从内在PIDDosome激活到化学调制。

IF 21.1 1区生物学

Protein & Cell Pub Date : 2024-04-27 DOI: 10.1093/procel/pwae020

Mengxue Zeng, Kun Wang, Qingcui Wu, Jingjin Ding, Dan Xie, Xiangbing Qi, Feng Shao

{"title":"Dissecting caspase-2-mediated cell death: from intrinsic PIDDosome activation to chemical modulation.","authors":"Mengxue Zeng, Kun Wang, Qingcui Wu, Jingjin Ding, Dan Xie, Xiangbing Qi, Feng Shao","doi":"10.1093/procel/pwae020","DOIUrl":"https://doi.org/10.1093/procel/pwae020","url":null,"abstract":"Caspase-2, a highly conserved member of the caspase family, is considered an initiator caspase that triggers apoptosis in response to some cellular stresses. Previous studies suggest that an intracellular multi-protein complex PIDDosome, induced by genotoxic stress, serves as a platform for caspase-2 activation. However, due to caspase-2's inability to process effector caspases, the mechanism underlying caspase-2-mediated cell death upon PIDDosome activation remains unclear. Here we conducted an unbiased genome-wide genetic screen and identified that the Bcl2 family protein BID is required for PIDDosome-induced, caspase-2-mediated apoptosis. PIDDosome-activated caspase-2 directly and functionally processes BID to signal the mitochondrial pathway for apoptosis induction. Additionally, a designed chemical screen identified a compound, HUHS015, that specifically activates caspase-2-mediated apoptosis. HUHS015-stimulated apoptosis also requires BID but is independent of the PIDDosome. Through extensive structure-activity relationship efforts, we identified a derivative with a potency of ~ 60 nmol/L in activating caspase-2-mediated apoptosis. The HUHS015-series of compounds act as efficient agonists that directly target the interdomain linker in caspase-2, representing a new mode of initiator caspase activation. Human and mouse caspase-2 differ in two crucial residues in the linker, rendering a selectivity of the agonists for human caspase-2. The caspase-2 agonists are valuable tools to explore the physiological roles of caspase-2-mediated cell death and a base for developing small-molecule drugs for relevant diseases.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":null,"pages":null},"PeriodicalIF":21.1,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140869069","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