Cell insightPub Date : 2023-04-01DOI: 10.1016/j.cellin.2023.100078
Xingxing Shao , Xin Liu , Hai Qi
{"title":"A role for Hes1 in constraining germinal center B cell formation","authors":"Xingxing Shao , Xin Liu , Hai Qi","doi":"10.1016/j.cellin.2023.100078","DOIUrl":"https://doi.org/10.1016/j.cellin.2023.100078","url":null,"abstract":"<div><p>Germinal center is a transient lymphoid tissue structure in which B cells undergo affinity maturation and differentiate into memory B cells and plasma cells. GC formation depends on B cell expression of BCL6, a master transcription regulator of the GC state. Bcl6 expression is under elaborate control by external signals. HES1 plays important roles in T-cell lineage commitment, although little is known about its potential roles in GC formation. Here we report that B-cell-specific HES1 deletion causes a significant increase in GC formation, leading to increased production of plasma cells. We further provide evidence that HES1 inhibits BCL6 expression in a bHLH domain-dependent manner. Our study suggests a new layer of regulation of GC initiation mediated by HES1 and, by inference, Notch signals <em>in vivo</em>.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"2 2","pages":"Article 100078"},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49777269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell insightPub Date : 2023-02-01DOI: 10.1016/j.cellin.2022.100068
Guangnan Li , Zhidong Tang , Weiliang Fan , Xi Wang , Li Huang , Yu Jia , Manli Wang , Zhihong Hu , Yu Zhou
{"title":"Atlas of interactions between SARS-CoV-2 macromolecules and host proteins","authors":"Guangnan Li , Zhidong Tang , Weiliang Fan , Xi Wang , Li Huang , Yu Jia , Manli Wang , Zhihong Hu , Yu Zhou","doi":"10.1016/j.cellin.2022.100068","DOIUrl":"10.1016/j.cellin.2022.100068","url":null,"abstract":"<div><p>The proteins and RNAs of viruses extensively interact with host proteins after infection. We collected and reanalyzed all available datasets of protein-protein and RNA-protein interactions related to SARS-CoV-2. We investigated the reproducibility of those interactions and made strict filters to identify highly confident interactions. We systematically analyzed the interaction network and identified preferred subcellular localizations of viral proteins, some of which such as ORF8 in ER and ORF7A/B in ER membrane were validated using dual fluorescence imaging. Moreover, we showed that viral proteins frequently interact with host machinery related to protein processing in ER and vesicle-associated processes. Integrating the protein- and RNA-interactomes, we found that SARS-CoV-2 RNA and its N protein closely interacted with stress granules including 40 core factors, of which we specifically validated G3BP1, IGF2BP1, and MOV10 using RIP and Co-IP assays. Combining CRISPR screening results, we further identified 86 antiviral and 62 proviral factors and associated drugs. Using network diffusion, we found additional 44 interacting proteins including two proviral factors previously validated. Furthermore, we showed that this atlas could be applied to identify the complications associated with COVID-19. All data are available in the AIMaP database (<span>https://mvip.whu.edu.cn/aimap/</span><svg><path></path></svg>) for users to easily explore the interaction map.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"2 1","pages":"Article 100068"},"PeriodicalIF":0.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1e/e4/main.PMC9670597.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9485001","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 : 2023-02-01DOI: 10.1016/j.cellin.2023.100077
Dong Guo , Ying Meng , Xiaoming Jiang , Zhimin Lu
{"title":"Hexokinases in cancer and other pathologies","authors":"Dong Guo , Ying Meng , Xiaoming Jiang , Zhimin Lu","doi":"10.1016/j.cellin.2023.100077","DOIUrl":"10.1016/j.cellin.2023.100077","url":null,"abstract":"<div><p>Glucose metabolism is indispensable for cell growth and survival. Hexokinases play pivotal roles in glucose metabolism through canonical functions of hexokinases as well as in immune response, cell stemness, autophagy, and other cellular activities through noncanonical functions. The aberrant regulation of hexokinases contributes to the development and progression of pathologies, including cancer and immune diseases.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"2 1","pages":"Article 100077"},"PeriodicalIF":0.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b8/33/main.PMC10120283.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10301099","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 : 2023-02-01DOI: 10.1016/j.cellin.2022.100076
Dan San , Jun Lei , Yang Liu , Baowei Jing, Xiang Ye, Pengcheng Wei, Chonil Paek, Yi Yang, Jin Zhou, Peng Chen, Hongjian Wang, Yongshun Chen, Lei Yin
{"title":"Structural basis of the TCR-pHLA complex provides insights into the unconventional recognition of CDR3β in TCR cross-reactivity and alloreactivity","authors":"Dan San , Jun Lei , Yang Liu , Baowei Jing, Xiang Ye, Pengcheng Wei, Chonil Paek, Yi Yang, Jin Zhou, Peng Chen, Hongjian Wang, Yongshun Chen, Lei Yin","doi":"10.1016/j.cellin.2022.100076","DOIUrl":"10.1016/j.cellin.2022.100076","url":null,"abstract":"<div><p>Evidence shows that some class I human leucocyte antigen (HLA) alleles are related to durable HIV controls. The T18A TCR, which has the alloreactivity between HLA-B∗42:01 and HLA-B∗81:01 and the cross-reactivity with different antigen mutants, can sustain long-term HIV controls. Here the structural basis of the T18A TCR binding to the immunodominant HIV epitope TL9 (TPQDLNTML180-188) presented by HLA-B∗42:01 was determined and compared to T18A TCR binding to the TL9 presented by the allo-HLA-B∗81:01. For differences between HLA-B∗42:01 and HLA-B∗81:01, the CDR1α and CDR3α loops adopt a small rearrangement to accommodate them. For different conformations of the TL9 presented by different HLA alleles, not like the conventional recognition of CDR3s to interact with peptide antigens, CDR3β of the T18A TCR shifts to avoid the peptide antigen but intensively recognizes the HLA only, which is different with other conventional TCR structures. Featured sequence pairs of CDR3β and HLA might account for this and were additionally found in multiple other diseases indicating the popularity of the unconventional recognition pattern which would give insights into the control of diseases with epitope mutating such as HIV.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"2 1","pages":"Article 100076"},"PeriodicalIF":0.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/58/27/main.PMC10120306.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9490704","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 : 2023-02-01DOI: 10.1016/j.cellin.2022.100075
Jiaxu Liu , Hao Huang , Minghao Zhang , Guoliang Qing , Hudan Liu
{"title":"Intertwined regulation between RNA m6A modification and cancer metabolism","authors":"Jiaxu Liu , Hao Huang , Minghao Zhang , Guoliang Qing , Hudan Liu","doi":"10.1016/j.cellin.2022.100075","DOIUrl":"https://doi.org/10.1016/j.cellin.2022.100075","url":null,"abstract":"<div><p>RNA N6-methyladenosine (m<sup>6</sup>A) has been identified as the most common, abundant and conserved internal modification in RNA transcripts, especially within eukaryotic messenger RNAs (mRNAs). Accumulating evidence demonstrates that RNA m<sup>6</sup>A modification exploits a wide range of regulatory mechanisms to control gene expression in pathophysiological processes including cancer. Metabolic reprogramming has been widely recognized as a hallmark of cancer. Cancer cells obtain metabolic adaptation through a variety of endogenous and exogenous signaling pathways to promote cell growth and survival in the microenvironment with limited nutrient supply. Recent emerging evidence reveals reciprocal regulation between the m<sup>6</sup>A modification and disordered metabolic events in cancer cells, adding more complexity in the cellular network of metabolic rewiring. In this review, we summarize the most recent advances of how RNA methylation affects tumor metabolism and the feedback regulation of m<sup>6</sup>A modification by metabolic intermediates. We aim to highlight the important connection between RNA m<sup>6</sup>A modification and cancer metabolism, and expect that studise of RNA m<sup>6</sup>A and metabolic reprogramming will lead to greater understanding of cancer pathology.</p></div>","PeriodicalId":72541,"journal":{"name":"Cell insight","volume":"2 1","pages":"Article 100075"},"PeriodicalIF":0.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49774143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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}