{"title":"p21/Zbtb18 repress the expression of cKit to regulate the self-renewal of hematopoietic stem cells.","authors":"Nini Wang, Shangda Yang, Yu Li, Fanglin Gou, Yanling Lv, Xiangnan Zhao, Yifei Wang, Chang Xu, Bin Zhou, Fang Dong, Zhenyu Ju, Tao Cheng, Hui Cheng","doi":"10.1093/procel/pwae022","DOIUrl":"10.1093/procel/pwae022","url":null,"abstract":"<p><p>The maintenance of hematopoietic stem cells (HSCs) is a complex process involving numerous cell-extrinsic and -intrinsic regulators. The first member of the cyclin-dependent kinase family of inhibitors to be identified, p21, has been reported to perform a wide range of critical biological functions, including cell cycle regulation, transcription, differentiation, and so on. Given the previous inconsistent results regarding the functions of p21 in HSCs in a p21-knockout mouse model, we employed p21-tdTomato (tdT) mice to further elucidate its role in HSCs during homeostasis. The results showed that p21-tdT+ HSCs exhibited increased self-renewal capacity compared to p21-tdT- HSCs. Zbtb18, a transcriptional repressor, was upregulated in p21-tdT+ HSCs, and its knockdown significantly impaired the reconstitution capability of HSCs. Furthermore, p21 interacted with ZBTB18 to co-repress the expression of cKit in HSCs and thus regulated the self-renewal of HSCs. Our data provide novel insights into the physiological role and mechanisms of p21 in HSCs during homeostasis independent of its conventional role as a cell cycle inhibitor.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"840-857"},"PeriodicalIF":13.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892325","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}
Protein & CellPub Date : 2024-11-01DOI: 10.1093/procel/pwad062
{"title":"Correction to: Oncogenic miR-19a and miR-19b co-regulate tumor suppressor MTUS1 to promote cell proliferation and migration in lung cancer.","authors":"","doi":"10.1093/procel/pwad062","DOIUrl":"10.1093/procel/pwad062","url":null,"abstract":"","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"866"},"PeriodicalIF":13.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139465601","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}
Protein & CellPub Date : 2024-11-01DOI: 10.1093/procel/pwae032
Junpeng Gao, Mengya Liu, Minjie Lu, Yuxuan Zheng, Yan Wang, Jingwei Yang, Xiaohui Xue, Yun Liu, Fuchou Tang, Shuiyun Wang, Lei Song, Lu Wen, Jizheng Wang
{"title":"Integrative analysis of transcriptome, DNA methylome, and chromatin accessibility reveals candidate therapeutic targets in hypertrophic cardiomyopathy.","authors":"Junpeng Gao, Mengya Liu, Minjie Lu, Yuxuan Zheng, Yan Wang, Jingwei Yang, Xiaohui Xue, Yun Liu, Fuchou Tang, Shuiyun Wang, Lei Song, Lu Wen, Jizheng Wang","doi":"10.1093/procel/pwae032","DOIUrl":"10.1093/procel/pwae032","url":null,"abstract":"<p><p>Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease and is characterized by primary left ventricular hypertrophy usually caused by mutations in sarcomere genes. The mechanism underlying cardiac remodeling in HCM remains incompletely understood. An investigation of HCM through integrative analysis at multi-omics levels will be helpful for treating HCM. DNA methylation and chromatin accessibility, as well as gene expression, were assessed by nucleosome occupancy and methylome sequencing (NOMe-seq) and RNA-seq, respectively, using the cardiac tissues of HCM patients. Compared with those of the controls, the transcriptome, DNA methylome, and chromatin accessibility of the HCM myocardium showed multifaceted differences. At the transcriptome level, HCM hearts returned to the fetal gene program through decreased sarcomeric and metabolic gene expression and increased extracellular matrix gene expression. In the DNA methylome, hypermethylated and hypomethylated differentially methylated regions were identified in HCM. At the chromatin accessibility level, HCM hearts showed changes in different genome elements. Several transcription factors, including SP1 and EGR1, exhibited a fetal-like pattern of binding motifs in nucleosome-depleted regions in HCM. In particular, the inhibition of SP1 or EGR1 in an HCM mouse model harboring sarcomere mutations markedly alleviated the HCM phenotype of the mutant mice and reversed fetal gene reprogramming. Overall, this study not only provides a high-precision multi-omics map of HCM heart tissue but also sheds light on the therapeutic strategy by intervening in the fetal gene reprogramming in HCM.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"796-817"},"PeriodicalIF":13.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141082074","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}
Protein & CellPub Date : 2024-10-29DOI: 10.1093/procel/pwae063
Xue Zhang, Jing Han, Yudong Wang, Li Feng, Zhisong Fan, Yu Su, Wenya Song, Lan Wang, Long Wang, Hui Jin, Jiayin Liu, Dan Li, Guiying Li, Yan Liu, Jing Zuo, Zhiyu Ni
{"title":"Microbiome, metabolome and transcriptome analyses in esophageal squamous cell carcinoma: Insights into immune modulation by F. nucleatum.","authors":"Xue Zhang, Jing Han, Yudong Wang, Li Feng, Zhisong Fan, Yu Su, Wenya Song, Lan Wang, Long Wang, Hui Jin, Jiayin Liu, Dan Li, Guiying Li, Yan Liu, Jing Zuo, Zhiyu Ni","doi":"10.1093/procel/pwae063","DOIUrl":"https://doi.org/10.1093/procel/pwae063","url":null,"abstract":"","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547022","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":"JMJD1C forms condensates to facilitate a RUNX1-dependent gene expression program shared by multiple types of AML cells.","authors":"Qian Chen,Saisai Wang,Juqing Zhang,Min Xie,Bin Lu,Jie He,Zhuoran Zhen,Jing Li,Jiajun Zhu,Rong Li,Pilong Li,Haifeng Wang,Christopher Vakoc,Robert G Roeder,Mo Chen","doi":"10.1093/procel/pwae059","DOIUrl":"https://doi.org/10.1093/procel/pwae059","url":null,"abstract":"JMJD1C, a member of the lysine demethylase 3 (KDM3) family, is universally required for the survival of several types of acute myeloid leukemia (AML) cells with different genetic mutations, representing a therapeutic opportunity with broad application. Yet how JMJD1C regulates the leukemic programs of various AML cells is largely unexplored. Here we show that JMJD1C interacts with the master hematopoietic transcription factor RUNX1, which thereby recruits JMJD1C to the genome to facilitate a RUNX1-driven transcriptional program that supports leukemic cell survival. The underlying mechanism hinges on the long N-terminal disordered region of JMJD1C, which harbors two inseparable abilities: condensate formation and direct interaction with RUNX1. This dual capability of JMJD1C may influence enhancer-promoter contacts crucial for the expression of key leukemic genes regulated by RUNX1. Our findings demonstrate a previously unappreciated role for the non-catalytic function of JMJD1C in transcriptional regulation, underlying a mechanism shared by different types of leukemias.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":"96 1","pages":""},"PeriodicalIF":21.1,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142490565","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}
Protein & CellPub Date : 2024-10-23DOI: 10.1093/procel/pwae057
Ying Liu,Yin Li,Peipei Zhang
{"title":"Stress granules and organelles: Coordinating cellular responses in health and disease.","authors":"Ying Liu,Yin Li,Peipei Zhang","doi":"10.1093/procel/pwae057","DOIUrl":"https://doi.org/10.1093/procel/pwae057","url":null,"abstract":"Membrane-bound organelles and membraneless organelles (MLOs) coordinate various biological processes within eukaryotic cells. Among these, stress granules (SGs) are significant cytoplasmic MLOs that form in response to cellular stress, exhibiting liquid-like properties alongside stable substructures. SGs interact with diverse organelles, thereby influencing cellular pathways that are critical in both health and disease contexts. This review discusses the interplay between SGs and organelles and explores the methodologies employed to analyze interactions between SGs and other MLOs. Furthermore, it highlights the pivotal roles SGs play in regulating cellular responses and the pathogenesis of ALS. Gaining insights into these interactions is essential for deciphering the mechanisms underlying both physiological processes and pathological conditions.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":"1 1","pages":""},"PeriodicalIF":21.1,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488214","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}