Cell insightPub Date : 2022-12-01DOI: 10.1016/j.cellin.2022.100059
Hao Zhang , Chengsan Wang , Keyi Zhang , Peter Muiruri Kamau , Anna Luo , Lifeng Tian , Ren Lai
{"title":"The role of TRPA1 channels in thermosensation","authors":"Hao Zhang , Chengsan Wang , Keyi Zhang , Peter Muiruri Kamau , Anna Luo , Lifeng Tian , Ren Lai","doi":"10.1016/j.cellin.2022.100059","DOIUrl":"10.1016/j.cellin.2022.100059","url":null,"abstract":"<div><p>Transient receptor potential ankyrin 1 (TRPA1) is a polymodal nonselective cation channel sensitive to different physical and chemical stimuli. TRPA1 is associated with many important physiological functions in different species and thus is involved in different degrees of evolution. TRPA1 acts as a polymodal receptor for the perceiving of irritating chemicals, cold, heat, and mechanical sensations in various animal species. Numerous studies have supported many functions of TRPA1, but its temperature-sensing function remains controversial. Although TRPA1 is widely distributed in both invertebrates and vertebrates, and plays a crucial role in tempreture sensing, the role of TRPA1 thermosensation and molecular temperature sensitivity are species-specific. In this review, we summarize the temperature-sensing role of TRPA1 orthologues in terms of molecular, cellular, and behavioural levels.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"1 6","pages":"Article 100059"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cd/6b/main.PMC10120293.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9488242","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}
Cell insightPub Date : 2022-12-01DOI: 10.1016/j.cellin.2022.100067
Hou-Yuan Qiu, Rui-Jin Ji, Ying Zhang
{"title":"Current advances of CRISPR-Cas technology in cell therapy","authors":"Hou-Yuan Qiu, Rui-Jin Ji, Ying Zhang","doi":"10.1016/j.cellin.2022.100067","DOIUrl":"10.1016/j.cellin.2022.100067","url":null,"abstract":"<div><p>CRISPR-Cas is a versatile genome editing technology that has been broadly applied in both basic research and translation medicine. Ever since its discovery, the bacterial derived endonucleases have been engineered to a collection of robust genome-editing tools for introducing frameshift mutations or base conversions at site-specific loci. Since the initiation of first-in-human trial in 2016, CRISPR-Cas has been tested in 57 cell therapy trials, 38 of which focusing on engineered CAR-T cells and TCR-T cells for cancer malignancies, 15 trials of engineered hematopoietic stem cells treating hemoglobinopathies, leukemia and AIDS, and 4 trials of engineered iPSCs for diabetes and cancer. Here, we aim to review the recent breakthroughs of CRISPR technology and highlight their applications in cell therapy.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"1 6","pages":"Article 100067"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10120314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9488245","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}
Cell insightPub Date : 2022-12-01DOI: 10.1016/j.cellin.2022.100058
Mengxin Liu , Jie Liu , Tong Zhang , Li Wang
{"title":"Direct cardiac reprogramming: Toward the era of multi-omics analysis","authors":"Mengxin Liu , Jie Liu , Tong Zhang , Li Wang","doi":"10.1016/j.cellin.2022.100058","DOIUrl":"10.1016/j.cellin.2022.100058","url":null,"abstract":"<div><p>Limited regenerative capacity of adult cardiomyocytes precludes heart repair and regeneration after cardiac injury. Direct cardiac reprograming that converts scar-forming cardiac fibroblasts (CFs) into functional induced-cardiomyocytes (iCMs) offers promising potential to restore heart structure and heart function. Significant advances have been achieved in iCM reprogramming using genetic and epigenetic regulators, small molecules, and delivery strategies. Recent researches on the heterogeneity and reprogramming trajectories elucidated novel mechanisms of iCM reprogramming at single cell level. Here, we review recent progress in iCM reprogramming with a focus on multi-omics (transcriptomic, epigenomic and proteomic) researches to investigate the cellular and molecular machinery governing cell fate conversion. We also highlight the future potential using multi-omics approaches to dissect iCMs conversion for clinal applications.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"1 6","pages":"Article 100058"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e1/d2/main.PMC10120284.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9488243","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}
Cell insightPub Date : 2022-12-01DOI: 10.1016/j.cellin.2022.100060
Lanfang Li , Bing Zhang , Xiaomei Tang , Quntao Yu , Aodi He , Youming Lu , Xinyan Li
{"title":"A selective degeneration of cholinergic neurons mediated by NRADD in an Alzheimer's disease mouse model","authors":"Lanfang Li , Bing Zhang , Xiaomei Tang , Quntao Yu , Aodi He , Youming Lu , Xinyan Li","doi":"10.1016/j.cellin.2022.100060","DOIUrl":"10.1016/j.cellin.2022.100060","url":null,"abstract":"<div><p>Cholinergic neurons in the basal forebrain constitute a major source of cholinergic inputs to the forebrain, modulate diverse functions including sensory processing, memory and attention, and are vulnerable to Alzheimer's disease (AD). Recently, we classified cholinergic neurons into two distinct subpopulations; calbindin D28K-expressing (D28K<sup>+</sup>) versus D28K-lacking (D28K<sup>−</sup>) neurons. Yet, which of these two cholinergic subpopulations are selectively degenerated in AD and the molecular mechanisms underlying this selective degeneration remain unknown. Here, we reported a discovery that D28K<sup>+</sup> neurons are selectively degenerated and this degeneration induces anxiety-like behaviors in the early stage of AD. Neuronal type specific deletion of NRADD effectively rescues D28K<sup>+</sup> neuronal degeneration, whereas genetic introduction of exogenous NRADD causes D28K<sup>−</sup> neuronal loss. This gain- and loss-of-function study reveals a subtype specific degeneration of cholinergic neurons in the disease progression of AD and hence warrants a novel molecular target for AD therapy.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"1 6","pages":"Article 100060"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10120297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9540883","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}
Cell insightPub Date : 2022-10-01DOI: 10.1016/j.cellin.2022.100057
Yueming Yuan , An Fang , Zongmei Wang , Bin Tian , Yuan Zhang , Baokun Sui , Zhaochen Luo , Yingying Li , Ming Zhou , Huanchun Chen , Zhen F. Fu , Ling Zhao
{"title":"Trim25 restricts rabies virus replication by destabilizing phosphoprotein","authors":"Yueming Yuan , An Fang , Zongmei Wang , Bin Tian , Yuan Zhang , Baokun Sui , Zhaochen Luo , Yingying Li , Ming Zhou , Huanchun Chen , Zhen F. Fu , Ling Zhao","doi":"10.1016/j.cellin.2022.100057","DOIUrl":"10.1016/j.cellin.2022.100057","url":null,"abstract":"<div><p>Tripartite motif-containing protein 25 (Trim25) is an E3 ubiquitin ligase that activates retinoid acid-inducible gene I (RIG-I) and promotes the antiviral interferon response. Recent studies have shown that Trim25 can bind and degrade viral proteins, suggesting a different mechanism of Trim25 on its antiviral effects. In this study, Trim25 expression was upregulated in cells and mouse brains after rabies virus (RABV) infection. Moreover, expression of Trim25 limited RABV replication in cultured cells. Overexpression of Trim25 caused attenuated viral pathogenicity in a mouse model that was intramuscularly injected with RABV. Further experiments confirmed that Trim25 inhibited RABV replication via two different mechanisms: an E3 ubiquitin ligase-dependent mechanism and an E3 ubiquitin ligase-independent mechanism. Specifically, the CCD domain of Trim25 interacted with RABV phosphoprotein (RABV-P) at amino acid (AA) position at 72 and impaired the stability of RABV-P via complete autophagy. This study reveals a novel mechanism by which Trim25 restricts RABV replication by destabilizing RABV-P, which is independent of its E3 ubiquitin ligase activity.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"1 5","pages":"Article 100057"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cc/ea/main.PMC10120326.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9540900","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}
Cell insightPub Date : 2022-10-01DOI: 10.1016/j.cellin.2022.100055
Gongsheng Yuan , Shu-ting Yang , Shuying Yang
{"title":"Endothelial RGS12 governs angiogenesis in inflammatory arthritis by controlling cilia formation and elongation via MYCBP2 signaling","authors":"Gongsheng Yuan , Shu-ting Yang , Shuying Yang","doi":"10.1016/j.cellin.2022.100055","DOIUrl":"10.1016/j.cellin.2022.100055","url":null,"abstract":"<div><p>Angiogenesis is the formation of new capillaries that plays an essential role in the pathogenesis of inflammatory arthritis. However, the cellular and molecular mechanisms remain unclear. Here, we provide the first evidence that regulator of G-protein signaling 12 (RGS12) promotes angiogenesis in inflammatory arthritis through governing ciliogenesis and cilia elongation in endothelial cells. The knockout of RGS12 inhibits the development of inflammatory arthritis with the reduction in clinical score, paw swelling, and angiogenesis. Mechanistically, RGS12 overexpression (OE) in endothelial cells increases cilia number and length, and thereby promotes cell migration and tube-like structure formation. The knockout of cilia marker protein Intraflagellar transport (IFT) 80 blocked the increase in cilia number and length caused by RGS12 OE. Moreover, the results from LC/MS and IP analysis showed that RGS12 is associated with cilia-related protein MYC binding protein 2 (MYCBP2), which enhances the phosphorylation of MYCBP2 to promote ciliogenesis in endothelial cells. These findings demonstrate that upregulation of RGS12 by inflammation enhances angiogenesis by promoting cilia formation and elongation via activation of MYCBP2 signaling during inflammatory arthritis pathogenesis.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"1 5","pages":"Article 100055"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/74/68/main.PMC10120324.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9840602","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}
Cell insightPub Date : 2022-10-01DOI: 10.1016/j.cellin.2022.100048
Ting Li
{"title":"The functions of polycomb group proteins in T cells","authors":"Ting Li","doi":"10.1016/j.cellin.2022.100048","DOIUrl":"10.1016/j.cellin.2022.100048","url":null,"abstract":"<div><p>T cells are involved in many aspects of adaptive immunity, including autoimmunity, anti-tumor activity, and responses to allergenic substances and pathogens. T cells undergo comprehensive epigenome remodeling in response to signals. Polycomb group (PcG) proteins are a well-studied complex of chromatin regulators, conserved in animals, and function in various biological processes. PcG proteins are divided into two distinct complexes: PRC1 (Polycomb repressive complex 1) and PRC2. PcG is correlated with the regulation of T cell development, phenotypic transformation, and function. In contrast, PcG dysregulation is correlated with pathogenesis of immune-mediated diseases and compromised anti-tumor responses. This review discusses recent findings on the involvement of PcG proteins in T cell maturation, differentiation, and activation. In addition, we explore implications in the development of the immune system diseases and cancer immunity, which offers promising targets for various treatment protocols.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"1 5","pages":"Article 100048"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0b/b0/main.PMC10120301.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9841054","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":"mRNA produced by VSW-3 RNAP has high-level translation efficiency with low inflammatory stimulation","authors":"Guoquan Wang , Rui Cheng , Qiubing Chen , Yuandong Xu , Bingbing Yu , Bin Zhu , Hao Yin , Heng Xia","doi":"10.1016/j.cellin.2022.100056","DOIUrl":"10.1016/j.cellin.2022.100056","url":null,"abstract":"<div><p><em>In vitro</em> preparation of mRNA is a key step for mRNA therapeutics. The widely used T7 RNA polymerase (RNAP) was shown to have many by-products during <em>in vitro</em> transcription (IVT) process, among which double-stranded RNA (dsRNA) is the major by-product to activate the intracellular immune response. Here, we describe the use of a new VSW-3 RNAP that reduced dsRNA production during IVT and the resulting mRNA exhibited low inflammatory stimulation in cells. Compared to T7 RNAP transcripts, these mRNA exhibited superior protein expression levels, with an average of 14-fold increase in Hela cells and 5-fold increase in mice. In addition, we found that VSW-3 RNAP did not require modified nucleotides to improve protein production of IVT products. Our data suggest that VSW-3 RNAP could be a useful tool for mRNA therapeutics.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"1 5","pages":"Article 100056"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/22/80/main.PMC10120321.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9840603","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}
Cell insightPub Date : 2022-08-01DOI: 10.1016/j.cellin.2022.100046
Timsy Uppal , Kai Tuffo , Svetlana Khaiboullina , Sivani Reganti , Mark Pandori , Subhash C. Verma
{"title":"Screening of SARS-CoV-2 antivirals through a cell-based RNA-dependent RNA polymerase (RdRp) reporter assay","authors":"Timsy Uppal , Kai Tuffo , Svetlana Khaiboullina , Sivani Reganti , Mark Pandori , Subhash C. Verma","doi":"10.1016/j.cellin.2022.100046","DOIUrl":"10.1016/j.cellin.2022.100046","url":null,"abstract":"<div><p>COVID-19 (Coronavirus Disease 2019) caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome CoronaVirus-2) continues to pose an international public health threat and thus far, has resulted in greater than 6.4 million deaths worldwide. Vaccines are critical tools to limit COVID-19 spread, but antiviral drug development is an ongoing global priority due to fast-spreading COVID-19 variants that may elude vaccine efficacies. The RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 is an essential enzyme of viral replication and transcription machinery complex. Therefore, the RdRp is an attractive target for the development of effective anti-COVID-19 therapeutics. In this study, we developed a cell-based assay to determine the enzymatic activity of SARS-CoV-2 RdRp through a luciferase reporter system. The SARS-CoV-2 RdRp reporter assay was validated using known inhibitors of RdRp polymerase, remdesivir along with other anti-virals including ribavirin, penciclovir, rhoifolin, 5′CT, and dasabuvir. Dasabuvir (an FDA-approved drug) exhibited promising RdRp inhibitory activity among these inhibitors. Anti-viral activity of dasabuvir was also tested on the replication of SARS-CoV-2 through infection of Vero E6 cells. Dasabuvir inhibited the replication of SARS-CoV-2, USA-WA1/2020 as well as B.1.617.2 (delta variant) in Vero E6 cells in a dose-dependent manner with EC<sub>50</sub> values 9.47 μM and 10.48 μM, for USA-WA1/2020 and B.1.617.2 variants, respectively. Our results suggest that dasabuvir can be further evaluated as a therapeutic drug for COVID-19. Importantly, this system provides a robust, target-specific, and high-throughput screening compatible (z- and z’-factors of >0.5) platforms that will be a valuable tool for screening SARS-CoV-2 RdRp inhibitors.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"1 4","pages":"Article 100046"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d8/14/main.PMC9239919.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9540492","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}