Genes & development最新文献_第2页

Chronic interferon-stimulated gene transcription promotes oncogene-induced breast cancer 慢性干扰素刺激基因转录促进癌基因诱发乳腺癌

IF 10.5 1区生物学

Genes & development Pub Date : 2024-10-25 DOI: 10.1101/gad.351455.123

Hexiao Wang, Claudia Canasto-Chibuque, Jun Hyun Kim, Marcel Hohl, Christina Leslie, Jorge S. Reis-Filho, John H.J. Petrini

{"title":"Chronic interferon-stimulated gene transcription promotes oncogene-induced breast cancer","authors":"Hexiao Wang, Claudia Canasto-Chibuque, Jun Hyun Kim, Marcel Hohl, Christina Leslie, Jorge S. Reis-Filho, John H.J. Petrini","doi":"10.1101/gad.351455.123","DOIUrl":"https://doi.org/10.1101/gad.351455.123","url":null,"abstract":"The MRE11 complex (comprising MRE11, RAD50, and NBS1) is integral to the maintenance of genome stability. We previously showed that a hypomorphic Mre11 mutant mouse strain (Mre11ATLD1/ATLD1) was highly susceptible to oncogene-induced breast cancer. Here we used a mammary organoid system to examine which MRE11-dependent responses are tumor-suppressive. We found that Mre11ATLD1/ATLD1 organoids exhibited an elevated interferon-stimulated gene (ISG) signature and sustained changes in chromatin accessibility. This Mre11ATLD1/ATLD1 phenotype depended on DNA binding of a nuclear innate immune sensor, IFI205. Ablation of Ifi205 in Mre11ATLD1/ATLD1 organoids restored baseline and oncogene-induced chromatin accessibility patterns to those observed in WT. Implantation of Mre11ATLD1/ATLD1 organoids and activation of the oncogene led to aggressive metastatic breast cancer. This outcome was reversed in implanted Ifi205−/− Mre11ATLD1/ATLD1 organoids. These data reveal a connection between innate immune signaling and tumor development in the mammary epithelium. Given the abundance of aberrant DNA structures that arise in the context of genome instability syndromes, the data further suggest that cancer predisposition in those contexts may be partially attributable to chronic innate immune transcriptional programs.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"194 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142490358","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

Circadian de(regulation) in physiology: implications for disease and treatment 生理学中的昼夜节律调节：对疾病和治疗的影响

IF 10.5 1区生物学

Genes & development Pub Date : 2024-10-17 DOI: 10.1101/gad.352180.124

Leonardo Vinicius Monteiro de Assis, Achim Kramer

{"title":"Circadian de(regulation) in physiology: implications for disease and treatment","authors":"Leonardo Vinicius Monteiro de Assis, Achim Kramer","doi":"10.1101/gad.352180.124","DOIUrl":"https://doi.org/10.1101/gad.352180.124","url":null,"abstract":"Time plays a crucial role in the regulation of physiological processes. Without a temporal control system, animals would be unprepared for cyclic environmental changes, negatively impacting their survival. Experimental studies have demonstrated the essential role of the circadian system in the temporal coordination of physiological processes. Translating these findings to humans has been challenging. Increasing evidence suggests that modern lifestyle factors such as diet, sedentarism, light exposure, and social jet lag can stress the human circadian system, contributing to misalignment; i.e., loss of phase coherence across tissues. An increasing body of evidence supports the negative impact of circadian disruption on several human health parameters. This review aims to provide a comprehensive overview of how circadian disruption influences various physiological processes, its long-term health consequences, and its association with various diseases. To illustrate the relevant consequences of circadian disruption, we focused on describing the many physiological consequences faced by shift workers, a population known to experience high levels of circadian disruption. We also discuss the emerging field of circadian medicine, its founding principles, and its potential impact on human health.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":"106 1","pages":""},"PeriodicalIF":10.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448383","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

YY1 knockout in pro-B cells impairs lineage commitment, enabling unusual hematopoietic lineage plasticity. 原 B 细胞中的 YY1 基因敲除会损害血系承诺，从而使造血血系具有不寻常的可塑性。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-10-16 DOI: 10.1101/gad.351734.124

Sarmistha Banerjee, Sulagna Sanyal, Suchita Hodawadekar, Sarah Naiyer, Nasreen Bano, Anupam Banerjee, Joshua Rhoades, Dawei Dong, David Allman, Michael L Atchison

{"title":"YY1 knockout in pro-B cells impairs lineage commitment, enabling unusual hematopoietic lineage plasticity.","authors":"Sarmistha Banerjee, Sulagna Sanyal, Suchita Hodawadekar, Sarah Naiyer, Nasreen Bano, Anupam Banerjee, Joshua Rhoades, Dawei Dong, David Allman, Michael L Atchison","doi":"10.1101/gad.351734.124","DOIUrl":"10.1101/gad.351734.124","url":null,"abstract":"During B-cell development, cells progress through multiple developmental stages, with the pro-B-cell stage defining commitment to the B-cell lineage. YY1 is a ubiquitous transcription factor that is capable of both activation and repression functions. We found here that knockout of YY1 at the pro-B-cell stage eliminates B lineage commitment. YY1 knockout pro-B cells can generate T lineage cells in vitro using the OP9-DL4 feeder system and in vivo after injection into sublethally irradiated Rag1-/- mice. These T lineage-like cells lose their B lineage transcript profile and gain a T-cell lineage profile. Single-cell RNA-seq experiments showed that as YY1 knockout pro-B cells transition into T lineage cells in vitro, various cell clusters adopt transcript profiles representing a multiplicity of hematopoietic lineages, indicating unusual lineage plasticity. In addition, YY1 KO pro-B cells in vivo can give rise to other hematopoietic lineages in vivo. Evaluation of RNA-seq, scRNA-seq, ChIP-seq, and scATAC-seq data indicates that YY1 controls numerous chromatin-modifying proteins leading to increased accessibility of alternative lineage genes in YY1 knockout pro-B cells. Given the ubiquitous nature of YY1 and its dual activation and repression functions, YY1 may regulate commitment in multiple cell lineages.","PeriodicalId":12591,"journal":{"name":"Genes & development","volume":" ","pages":"887-914"},"PeriodicalIF":7.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371578","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

The area postrema: a critical mediator of brain-body interactions. 脑后区：脑-体互动的关键中介。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-10-16 DOI: 10.1101/gad.352276.124

Daniëlle van de Lisdonk, Bo Li

引用次数: 0

Cancer neuroscience at the brain-body interface. 脑-体界面的癌症神经科学。

IF 7.5 1区生物学

Genes & development Pub Date : 2024-10-16 DOI: 10.1101/gad.352288.124

Jeremy C Borniger

引用次数: 0

What a wonderful world! 世界真奇妙