keyword
https://read.qxmd.com/read/38521877/maternal-rna-transcription-in-dlk1-dio3-domain-is-critical-for-proper-development-of-the-mouse-placental-vasculature
#1
JOURNAL ARTICLE
Ximeijia Zhang, Hongjuan He, Haoran Yu, Xiangqi Teng, Ziwen Wang, Chenghao Li, Jiahang Li, Haopeng Yang, Jiwei Shen, Tong Wu, Fengwei Zhang, Yan Zhang, Qiong Wu
The placenta is a unique organ for ensuring normal embryonic growth in the uterine. Here, we found that maternal RNA transcription in Dlk1-Dio3 imprinted domain is essential for placentation. PolyA signals were inserted into Gtl2 to establish a mouse model to prevent the expression of maternal RNAs in the domain. The maternal allele knock-in (MKI) and homozygous (HOMO) placentas showed an expanded junctional zone, reduced labyrinth and poor vasculature impacting both fetal and maternal blood spaces. The MKI and HOMO models displayed dysregulated gene expression in the Dlk1-Dio3 domain...
March 23, 2024: Communications Biology
https://read.qxmd.com/read/38434968/-trim67-promotes-non-small-cell-lung-cancer-development-by-positively-regulating-the-notch-pathway-through-dlk1-ubiquitination
#2
JOURNAL ARTICLE
Jun Jiang, Xinjie Dong, Jixuan Liu, Ting Liu, Xiaoshuai Chen, Xiaolei Bian, Ming Li, Yafang Liu
Tripartite motif-containing 67 (TRIM67), a member of the TRIM protein family, is an E3 ubiquitin ligase. Our previous study revealed a relationship between TRIM67 expression and carcinogenesis, showing that TRIM67 expression is linked to p-TNM stage, lymph node metastasis, tumour size, cancer cell differentiation, and poor prognosis. Additionally, TRIM67 immunostaining results were associated with clinicopathological features. TRIM67 activated the Notch pathway in a favourable manner to enhance cell invasion, migration, and proliferation...
2024: Journal of Cancer
https://read.qxmd.com/read/38425435/gene-regulation-and-mitochondrial-activity-during-white-and-brown-adipogenesis-are-modulated-by-kdm5-histone-demethylase
#3
JOURNAL ARTICLE
Laurent Vergnes, Carrie B Wiese, Temeka Zore, Carrie Riestenberg, Rozeta Avetisyan, Karen Reue
Body fat accumulation differs between males and females and is influenced by both gonadal sex (ovaries vs testes) and chromosomal sex (XX vs XY). We previously showed that an X chromosome gene, Kdm5c , is expressed at higher levels in females compared to males and correlates with adiposity in mice and humans. Kdm5c encodes a KDM5 histone demethylase that regulates gene expression by modulating histone methylation at gene promoters and enhancers. Here, we use chemical inhibition and genetic knockdown to identify a role for KDM5 activity during early stages of white and brown preadipocyte differentiation, with specific effects on white adipocyte clonal expansion, and white and brown adipocyte gene expression and mitochondrial activity...
February 19, 2024: Journal of the Endocrine Society
https://read.qxmd.com/read/38367171/novel-variants-ensued-genomic-imprinting-in-familial-central-precocious-puberty
#4
JOURNAL ARTICLE
V Karaman, E Karakilic-Ozturan, S Poyrazoglu, M Y Gelmez, F Bas, F Darendeliler, Z O Uyguner
INTRODUCTION: Central precocious puberty (CPP) is characterized by the early onset of puberty and is associated with the critical processes involved in the pubertal switch. The puberty-related gene pool in the human genome is considerably large though few have been described in CPP. Within those genes, the genomic imprinting features of the MKRN3 and DLK1 genes add additional complexity to the understanding of the pathologic pathways. This study aimed to investigate the molecular etiology in the CPP cohort...
February 17, 2024: Journal of Endocrinological Investigation
https://read.qxmd.com/read/38328889/pericardial-delta-like-non-canonical-notch-ligand-1-dlk1-augments-fibrosis-in-the-heart-through-epithelial-to-mesenchymal-transition
#5
JOURNAL ARTICLE
Charlotte Harken Jensen, Rikke Helin Johnsen, Tilde Eskildsen, Christina Baun, Ditte Gry Ellman, Shu Fang, Sara Thornby Bak, Svend Hvidsten, Lars Allan Larsen, Ann Mari Rosager, Lars Peter Riber, Mikael Schneider, Jo De Mey, Mads Thomassen, Mark Burton, Shizuka Uchida, Jorge Laborda, Ditte Caroline Andersen
BACKGROUND: Heart failure due to myocardial infarction (MI) involves fibrosis driven by epicardium-derived cells (EPDCs) and cardiac fibroblasts, but strategies to inhibit and provide cardio-protection remains poor. The imprinted gene, non-canonical NOTCH ligand 1 (Dlk1), has previously been shown to mediate fibrosis in the skin, lung and liver, but very little is known on its effect in the heart. METHODS: Herein, human pericardial fluid/plasma and tissue biopsies were assessed for DLK1, whereas the spatiotemporal expression of Dlk1 was determined in mouse hearts...
February 2024: Clinical and Translational Medicine
https://read.qxmd.com/read/38328230/dual-effects-of-arx-poly-alanine-mutations-in-human-cortical-and-interneuron-development
#6
Vanesa Nieto-Estevez, Parul Varma, Sara Mirsadeghi, Jimena Caballero, Sergio Gamero-Alameda, Ali Hosseini, Sonal Goswami, Marc J Silvosa, Drew M Thodeson, Zane R Lybrand, Michele Giugliano, Christopher Navara, Jenny Hsieh
Mutations in ARX , an X-linked gene, are implicated in a wide spectrum of neurological disorders including patients who have intellectual disability and epilepsy. Mouse models have shown that Arx is critical for cortical development and interneuron migration, however they do not recapitulate the full phenotype observed in patients. Moreover, the epilepsy in many patients with poly-alanine tract expansion (PAE) mutations in ARX show pharmacoresistance, emphasizing the need to develop new treatments. Here, we used human neural organoid models to study the consequences of PAE mutations, one of the most prevalent mutations in ARX ...
January 25, 2024: bioRxiv
https://read.qxmd.com/read/38328172/identification-of-type-2-diabetes-and-obesity-associated-human-%C3%AE-cells-using-deep-transfer-learning
#7
Gitanjali Roy, Rameesha Syed, Olivia Lazaro, Sylvia Robertson, Sean D McCabe, Daniela Rodriguez, Alex M Mawla, Travis S Johnson, Michael A Kalwat
Diabetes affects >10% of adults worldwide and is caused by impaired production or response to insulin, resulting in chronic hyperglycemia. Pancreatic islet β-cells are the sole source of endogenous insulin and our understanding of β-cell dysfunction and death in type 2 diabetes (T2D) is incomplete. Single-cell RNA-seq data supports heterogeneity as an important factor in β-cell function and survival. However, it is difficult to identify which β-cell phenotypes are critical for T2D etiology and progression...
January 23, 2024: bioRxiv
https://read.qxmd.com/read/38311851/dlk1-dio3-locus-upregulation-by-a-%C3%AE-catenin-dependent-enhancer-drives-cell-proliferation-and-liver-tumorigenesis
#8
JOURNAL ARTICLE
Julie Sanceau, Lucie Poupel, Camille Joubel, Isabelle Lagoutte, Stefano Caruso, Sandra Pinto, Christèle Desbois-Mouthon, Cécile Godard, Akila Hamimi, Enzo Montmory, Cécile Dulary, Sophie Chantalat, Amélie Roehrig, Kevin Muret, Benjamin Saint-Pierre, Jean-François Deleuze, Sophie Mouillet-Richard, Thierry Forné, Christophe F Grosset, Jessica Zucman-Rossi, Sabine Colnot, Angélique Gougelet
The CTNNB1 gene, encoding β-catenin, is frequently mutated in hepatocellular carcinoma (HCC, ∼30%) and in hepatoblastoma (HB, >80%), in which DLK1/DIO3 locus induction is correlated with CTNNB1 mutations. Here, we aim to decipher how sustained β-catenin activation regulates DLK1/DIO3 locus expression and the role this locus plays in HB and HCC development in mouse models deleted for Apc (ApcΔhep ) or Ctnnb1-exon 3 (β-cateninΔExon3 ) and in human CTNNB1-mutated hepatic cancer cells...
February 3, 2024: Molecular Therapy
https://read.qxmd.com/read/38296740/placenta-accreta-spectrum-disorder-at-single-cell-resolution-a-loss-of-boundary-limits-in-the-decidua-and-endothelium
#9
JOURNAL ARTICLE
Yalda Afshar, Ophelia Yin, Anhyo Jeong, Guadalupe Martinez, Jina Kim, Feiyang Ma, Christine Jang, Sarah Tabatabaei, Sungyong You, Hsian-Rong Tseng, Yazhen Zhu, Deborah Krakow
BACKGROUND: Placenta accreta spectrum disorders are associated with severe maternal morbidity and mortality. Placenta accreta spectrum disorders involve excessive adherence of the placenta preventing separation at birth. Traditionally, this condition has been attributed to excessive trophoblast invasion; however, an alternative view is a fundamental defect in decidual biology. OBJECTIVE: This study aimed to gain insights into the understanding of placenta accreta spectrum disorder by using single-cell and spatially resolved transcriptomics to characterize cellular heterogeneity at the maternal-fetal interface in placenta accreta spectrum disorders...
January 29, 2024: American Journal of Obstetrics and Gynecology
https://read.qxmd.com/read/38260367/distinct-human-stem-cell-subpopulations-drive-adipogenesis-and-fibrosis-in-musculoskeletal-injury
#10
Steven M Garcia, Justin Lau, Agustin Diaz, Hannah Chi, Miguel Lizarraga, Aboubacar Wague, Cristhian Montenegro, Michael R Davies, Xuhui Liu, Brian T Feeley
Fibroadipogenic progenitors (FAPs) maintain healthy skeletal muscle in homeostasis but drive muscle degeneration in chronic injuries by promoting adipogenesis and fibrosis. To uncover how these stem cells switch from a pro-regenerative to pro-degenerative role we perform single-cell mRNA sequencing of human FAPs from healthy and injured human muscles across a spectrum of injury, focusing on rotator cuff tears. We identify multiple subpopulations with progenitor, adipogenic, or fibrogenic gene signatures. We utilize full spectrum flow cytometry to identify distinct FAP subpopulations based on highly multiplexed protein expression...
January 5, 2024: bioRxiv
https://read.qxmd.com/read/38217981/a-fanca-knockout-mouse-model-reveals-novel-fancd2-function
#11
JOURNAL ARTICLE
Qian Wang, Jia Liu, Yixinhe Zhong, Dongbo Li, Yusen Zhong, Huazhong Ying, Tingting Zhang
Fanconi anemia (FA) is a genetically and clinically heterogenous inherited disorder. Clinically, Fanca subtype patients exhibited milder phenotypes compared to Fancd2 subtypes. Increasing evidence suggests that Fancd2 perform independent functions, but the detailed mechanisms are not well characterized. In this study, we developed a Fanca KO mice model in C57BL/6 background with ATG region deletion, then performed a detailed FA phenotypes characterization and analysis with Fanca KO mice and Fancd2 KO mice in the same congenic background...
December 31, 2023: Biochemical and Biophysical Research Communications
https://read.qxmd.com/read/38203302/effects-of-adipose-tissue-specific-knockout-of-delta-like-non-canonical-notch-ligand-1-on-lipid-metabolism-in-mice
#12
JOURNAL ARTICLE
Xin Lu, Xibi Fang, Jiaqi Mi, Yue Liu, Ruimin Liu, Guanghui Li, Yue Li, Runjun Yang
Delta-like non-canonical Notch ligand 1 ( DLK1 ), which inhibits the differentiation of precursor adipocytes, is a recognized marker gene for precursor adipocytes. Lipids play a crucial role in energy storage and metabolism as a vital determinant of beef quality. In this study, we investigated the mechanism of the DLK1 gene in lipid metabolism by constructing adipose tissue-specific knockout mice. We examined some phenotypic traits, including body weight, liver coefficient, fat index, the content of triglyceride (TG) and cholesterol (CHOL) in abdominal white adipose tissue (WAT) and blood...
December 21, 2023: International Journal of Molecular Sciences
https://read.qxmd.com/read/38201476/mir-410-is-a-key-regulator-of-epithelial-to-mesenchymal-transition-with-biphasic-role-in-prostate-cancer
#13
JOURNAL ARTICLE
Diana M Asante, Amritha Sreekumar, Sandip Nathani, Tae Jin Lee, Ashok Sharma, Nikhil Patel, Matthew N Simmons, Sharanjot Saini
The molecular basis of prostate cancer (PCa) progression from the primary disease to metastatic castration-resistant prostate cancer (CRPC) followed by therapy-induced neuroendocrine prostate cancer is not fully understood. In this study, we elucidate the role of miR-410, a little-studied microRNA located on chromosome 14q32.31 within the DLK1-DIO3 cluster, in PCa. miR-410 expression analyses in primary and metastatic PCa tissues and cell lines show that its levels are decreased in initial stages and increased in advanced PCa...
December 21, 2023: Cancers
https://read.qxmd.com/read/38184718/mendelian-randomization-identifies-circulating-proteins-as-biomarkers-for-age-at-menarche-and-age-at-natural-menopause
#14
JOURNAL ARTICLE
Nahid Yazdanpanah, Basile Jumentier, Mojgan Yazdanpanah, Ken K Ong, John R B Perry, Despoina Manousaki
Age at menarche (AAM) and age at natural menopause (ANM) are highly heritable traits and have been linked to various health outcomes. We aimed to identify circulating proteins associated with altered ANM and AAM using an unbiased two-sample Mendelian randomization (MR) and colocalization approach. By testing causal effects of 1,271 proteins on AAM, we identified 22 proteins causally associated with AAM in MR, among which 13 proteins (GCKR, FOXO3, SEMA3G, PATE4, AZGP1, NEGR1, LHB, DLK1, ANXA2, YWHAB, DNAJB12, RMDN1 and HPGDS) colocalized...
January 6, 2024: Communications Biology
https://read.qxmd.com/read/38155837/epigenetic-control-and-genomic-imprinting-dynamics-of-the-dlk1-dio3-domain
#15
REVIEW
Ariella Weinberg-Shukron, Neil A Youngson, Anne C Ferguson-Smith, Carol A Edwards
Genomic imprinting is an epigenetic process whereby genes are monoallelically expressed in a parent-of-origin-specific manner. Imprinted genes are frequently found clustered in the genome, likely illustrating their need for both shared regulatory control and functional inter-dependence. The Dlk1-Dio3 domain is one of the largest imprinted clusters. Genes in this region are involved in development, behavior, and postnatal metabolism: failure to correctly regulate the domain leads to Kagami-Ogata or Temple syndromes in humans...
2023: Frontiers in Cell and Developmental Biology
https://read.qxmd.com/read/38153351/egr2-deletion-in-autoimmune-prone-c57bl6-lpr-mice-suppresses-the-expression-of-methylation-sensitive-dlk1-dio3-cluster-micrornas
#16
JOURNAL ARTICLE
Zhuang Wang, Bettina Heid, Jianlin He, Hehuang Xie, Christopher M Reilly, Rujuan Dai, S Ansar Ahmed
We previously demonstrated that the upregulation of microRNAs (miRNAs) at the genomic imprinted Dlk1-Dio3 locus in murine lupus is correlated with global DNA hypomethylation. We now report that the Dlk1-Dio3 genomic region in CD4+ T cells of MRL/lpr mice is hypomethylated, linking it to increased Dlk1-Dio3 miRNA expression. We evaluated the gene expression of methylating enzymes, DNA methyltransferases (DNMTs), and demethylating ten-eleven translocation proteins (TETs) to elucidate the molecular basis of DNA hypomethylation in lupus CD4+ T cells...
December 1, 2023: ImmunoHorizons
https://read.qxmd.com/read/38134840/bone-marrow-adipocytes-is-a-new-player-in-supporting-myeloma-cells-proliferation-and-survival-in-myeloma-microenvironment
#17
JOURNAL ARTICLE
Xiaoqian Wei, Yangmin Zhang, Ziyan Wang, Yuanning He, Songguang Ju, Jinxiang Fu
Multiple myeloma (MM) is a lethal B cell neoplasm characterized by clonal expansion of malignant plasma cells in the bone marrow and remains incurable due to disease relapse and drug resistance. Bone marrow adipocytes (BMAs) are emerging as playing active functions that can support myeloma cell growth and survival. The aim of this study is to investigate myeloma-mesenchymal stem cells (MSCs) interaction and the impact of such interactions on the pathogenesis of MM using in vitro co-culture assay. Here we provide evidence that MM cell up-regulated MSCs to express PPAR-γ and pushes MSCs differentiation toward adipocytes at the expense of osteoblasts in co-culture manner...
December 21, 2023: Translational Oncology
https://read.qxmd.com/read/38106022/a-proteogenomic-surfaceome-study-identifies-dlk1-as-an-immunotherapeutic-target-in-neuroblastoma
#18
Amber K Weiner, Alexander B Radaoui, Matthew Tsang, Daniel Martinez, Simone Sidoli, Karina L Conkrite, Alberto Delaidelli, Apexa Modi, Jo Lynne Rokita, Khushbu Patel, Maria V Lane, Bo Zhang, Chuwei Zhong, Brian Ennis, Daniel P Miller, Miguel A Brown, Komal S Rathi, Pichai Raman, Jennifer Pogoriler, Tricia Bhatti, Bruce Pawel, Tina Glisovic-Aplenc, Beverly Teicher, Stephen W Erickson, Eric J Earley, Kristopher R Bosse, Poul H Sorensen, Kateryna Krytska, Yael P Mosse, Karin E Havenith, Francesca Zammarchi, Patrick H van Berkel, Malcolm A Smith, Benjamin A Garcia, John M Maris, Sharon J Diskin
UNLABELLED: Cancer immunotherapies have produced remarkable results in B-cell malignancies; however, optimal cell surface targets for many solid cancers remain elusive. Here, we present an integrative proteomic, transcriptomic, and epigenomic analysis of tumor specimens along with normal tissues to identify biologically relevant cell surface proteins that can serve as immunotherapeutic targets for neuroblastoma, an often-fatal childhood cancer of the developing nervous system. We apply this approach to human-derived cell lines (N=9) and cell/patient-derived xenograft (N=12) models of neuroblastoma...
December 8, 2023: bioRxiv
https://read.qxmd.com/read/38100614/maternal-adverse-childhood-experiences-aces-and-offspring-imprinted-gene-dmr-methylation-at-birth
#19
JOURNAL ARTICLE
Adriana C Vidal, David W Sosnowski, Joddy Marchesoni, Carole Grenier, John Thorp, Susan K Murphy, Sara B Johnson, Billy Schlief, Cathrine Hoyo
Adverse childhood experiences (ACEs) contribute to numerous negative health outcomes across the life course and across generations. Here, we extend prior work by examining the association of maternal ACEs, and their interaction with financial stress and discrimination, with methylation status within eight differentially methylated regions (DMRs) in imprinted domains in newborns. ACEs, financial stress during pregnancy, and experience of discrimination were self-reported among 232 pregnant women. DNA methylation was assessed at PEG10 / SGCE, NNAT, IGF2, H19, PLAGL1 , PEG3 , MEG3-IG , and DLK1/MEG3 regulatory sequences using pyrosequencing...
December 2024: Epigenetics: Official Journal of the DNA Methylation Society
https://read.qxmd.com/read/38092161/identification-and-validation-of-stable-reference-genes-for-expression-profiling-of-target-genes-in-diverse-ovine-tissues
#20
JOURNAL ARTICLE
Mahanthi Vasu, Sonika Ahlawat, Vikas Choudhary, Rashmeet Kaur, Reena Arora, Rekha Sharma, Upasna Sharma, Pooja Chhabra, M A Mir, Manoj Kumar Singh
Quantitative PCR (qPCR) is a widely-used technique for quantifying the expression of target genes across various tissues, as well as under different pathological and physiological conditions. One of the challenges associated with this method is the need to identify optimal reference genes (RGs) that maintain consistent expression levels under diverse experimental settings, thereby ensuring accurate biological interpretation. In this study, we conducted a thorough analysis of 18 candidate RGs (ACTB, BACH1, B2M, GAPDH, HMBS, HPRT1, PGK1, PPIA, PPIB, RPLP0, RPL19, RPS9, RPS15, RPS28, SDHA, TBP, UXT, and YWHAZ) across 10 ovine tissues (muscle, skin, kidney, liver, intestine, rumen, lung, testis, heart, and spleen) obtained from five individual sheep...
December 11, 2023: Gene
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