title: Effects of oxytocin on the hair growth ability of dermal papilla cells

city: Kawasaki

first: Tatsuto

last: Kageyama

state: Kanagawa

address: Life Innovation Center, 3-25-22 Tonomachi

institute: Kanagawa Institute of Industrial Science and Technology

summary: Oxytocin (OXT) is a neuropeptide hormone termed “love hormone” that is produced and released during childbirth and lactation. It is also produced in response to stimulation of the skin (e.g., during hugging and massaging) and music therapy, among others. The effects of OXT on various organs have been revealed in recent years; however, the relationship between hair follicles and OXT remains unclear. In this study, we examined the effects of OXT on dermal papilla (DP) cells, that control hair growth by secreting growth/regression signals. Gene expression analysis revealed that DP functional markers were significantly upregulated in DP cells treated with OXT. In addition, we tested the hair growth-promoting effects of OXT using in vitro hair follicle organoids. OXT promoted the growth of hair peg-like sprouting by upregulating the expression of hair growth-promoting factors including genes encoding vascular endothelial growth factor A (VEGFA). This study highlights the positive effects of OXT in hair follicles and may assist in the development of new treatments for alopecia.

overall_design: We analyzed gene expression of human dermal papilla cells with/without 10 μM OXT treatment for 6 days.

first: Junji

last: Fukuda


title: Pulmonary effects of inhaled diesel exhaust and fracking sand particles in rats

status: Public on Dec 01 2024

city: Morgantown

first: Pius

last: Joseph

address: 1000 Frederick Lane

country: USA

institute: NIOSH

type: Expression profiling by high throughput sequencing

summary: The pulmonary response to inhalation exposure to diesel exhaust particles (DEP) and fracking sand particles (FSD) was investigated in a rat model.  Healthy adult male Sprague-Dawley rats were exposed by whole-body inhalation to air (control) or an aerosol containing DEP at a concentration of 1.0 mg/m3 combined with FSD at concentrations of 30 mg/m3, 6 hours/day for 4 days.  The control and DEP/FSD exposed rats were euthanized at post-exposure time intervals of 1, 7, or 27 days and pulmonary inflammatory, cytotoxic, and oxidant responses were determined.  Analysis of bronchoalveolar lavage parameters of toxicity such as lactate dehydrogenase activity, oxidant generation, and inflammation revealed only minimal changes in pulmonary toxicity in the DEP/FSD-exposed rats, compared with the time-matched controls. The lung gene expression profiles showed only minimal changes in the DEP/FSD exposed rats compared with the controls. Specifically, there were a total of 6 genes significantly differentially expressed (fold change >1.5 and FDR p<0.05) only at the one-day post-exposure group. The data obtained from the present study demonstrated that DEP/FSD inhalation exposure, under the conditions employed in the present study, resulted in only minimal changes in lung toxicity and gene expression profile in the rats.

overall_design: The rats were exposed by inhalation to filtered air or 30 mg/m3 fracking sand dust and 1.0 mg/m3 of Diesel particles (6 hours/day for 4 days) . At post exposure time intervals of 1, 7, and 27 days, the  rats were euthanized and lung samples (n=8  were used to determine gene expression profiles by RNA sequencing.

first: Tina

middle: M

last: Sager


title: Effect of chaperonin 60 kDa on gene expression during osteoclast differentiation of RAW 264.7 cells

city: Seoul

first: Heeeun

last: Woo

address: 1, Anam-dong 5(o)-ga, Seongbuk-gu

country: South Korea

institute: Korea University

summary: To investigate the function of chaperonin 60 kDa in the inhibition of osteoclast differentiation, we performed gene expression profiling analysis using data obtained from RNA-seq.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for RAW 264.7 cells.

first: Younghee

last: Lim

first: Jooyoung

last: Cho


title: Inflammatory signature of atopic dermatitis from tissue and systemic levels

city: Taipei

first: Chen-Hsin

last: Wang

address: Zhongshan S. Rd

country: Taiwan

institute: National Taiwan University Hospital and College of Medicine

summary: We aimed to feature Asian populations and identify potential biomarkers associated with disease severity by incorporating analyses of skin and serum using RNA-seq

overall_design: Comparative gene expression profiling analysis of RNA-seq data for atopic dermatitis and normal patients.

first: Tom

middle: C

last: Chan


title: Hypoxia-induced gene expression profiling of esophageal cancer cell lines

city: Changchun

first: Tongjian

last: Zhao

address: 1266 Fujin Road

country: China

institute: School of Pharmaceutical Sciences, Jilin University

summary: Analysis of gene expression changes in two esophageal squamous cell carcinomas cell lines treated with hypoxia.

overall_design: RNA-seq analysis of gene expression in KYSE150 and KYSE410 incubated in 21% oxygen and 0.5% oxygen for 48 hours

first: Xiaoke

last: Di

first: Jiahang

last: Song


title: Meningioma cell lines CH-157MN and IOMM-Lee treated with digitoxin and torin 2

city: Evanston

first: Thomas

middle: P

last: Wytock

state: IL

address: 633 Clark St

department: Physics

institute: Northwestern University

summary: Meningiomas are central nervous system cancers that originate the membranes that surround the brain and spinal cord. To date, there is a lack of effective drug treatment options. This project used a drug combination prediction algorithm to arrive at digitoxin and torin 2 as a potentially effective pairwise combination. RNA-sequencing data was collected from the untreated, digitoxin treated, torin 2-treated, and combination-treated CH-157MN and IOMM-Lee cell lines to experimentally validate the prediction algorithm.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for CH-157MN and IOMM-Lee cells subjected to DMSO, digitoxin (78 nM), torin 2 (2 nM), or digitoxin (78 nM) and torin 2 treatment (2 nM).


title: A novel gene fusion RUNX1/ZNF423 promotes leukemic relapse of NUP98-rearranged AML

city: Hangzhou

first: Xuejing

last: Shao

address: 866, Yuhangtang Road

department: Zhejiang University

institute: College of Pharmaceutical Sciences

summary: Acute myeloid leukemia (AML) is characterized by serious aggressivity of high relapse risk and various molecular aberrations. Rearrangements involving NUP98 with multiple fusing partner genes in myeloid malignancies indicate dismal survival outcomes. Mechanisms contributing to subsequent aggressive progression and severe relapse risk of NUP98-rearranged AML remain undefined. Here we identified a novel oncogenic fusion RUNX1/ZNF423 in a relapse and refractory AML patient with NUP98/NSD1. And mice xenografted from the patient bearing both RUNX1/ZNF423 and NUP98/NSD1 display more severe engraftment levels than NUP98/NSD1 only. Mechanically, RUNX1/ZNF423 accompanied with NUP98/NSD1 recapitulated transcriptional signatures in hematopoietic differentiation blockage and altered amino acid metabolism pathway. Moreover, single-cell sequencing confirmed the coexistence of RUNX1/ZNF423 with NUP98/NSD1 in the same leukemic blast. Meanwhile, we also found that the coexistence of gene fusions in NUP98-rearranged AML was a significant phenomenon, which probably contributes to their worse clinical outcome. Finally, tailored intervention treatment based on ex vivo drug sensitivity testing is provided to this relapse and refractory AML patient and achieved favorable clinical response. Taken together, we not only identified a novel gene fusion RUNX1/ZNF423 with transforming potential detected in a NUP98-rearranged AML, but also achieved a deeper understanding into mechanisms contributing to disease relapse in AML.

overall_design: Mononuclear cells derived from the patient were conducted with scRNA-seq.

first: Meidan

last: Ying

first: Xiaojun

last: Xu

first: Wenxin

last: Du


title: Effect of osteocytes mitochondria on OA chondrocytes

city: Shanghai

first: Junjie

last: Gao

address: 600 Yishan Road

institute: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

summary:
To investigate the regulatory role of MLO-Y4 mitochondria on OA chondrocytes, we isolated mitochondria from MLO-Y4 and transplanted to chondrocytes treated with IL-1β.
We then performed gene expression profiling analysis using data obtained from RNA-seq of chondrocytes from vehicle group and mitochondria transplanted group.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for OA chondrocytes and OA chondrocytes transplanted with mitochondria.

first: Yiyang

last: Ma

first: Changqing

last: Zhang


title: A novel gene fusion RUNX1/ZNF423 promotes leukemic relapse of NUP98-rearranged AML [RNAseq]

overall_design: Gene expression profiling analysis of RNA-seq data for mononuclear cells derived from the patient and PDX mice.


title: Synergism of FAK and ROS1 inhibitors in the treatment of CDH1-deficient cancers mediated by FAK-YAP-TRX signaling

city: shanghai

first: Jiam

address: 197 Rui Jin 2nd Road

institute: Shanghai Institute of Hematology,Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine

summary:
To investigate the ROS1 and FAK inhibitors combination may provide stronger anti-cancer effects by targeting CDH1 deficiency and potentially overcome drug resistance.
Here, we evaluated the effects and mechanisms of combined treatment with FAK inhibitor IN10018 and ROS1 inhibitors.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for NUGC-4 cells by fifferent treament (IN10018 or Crizotinib monotherapy, IN10018 and Crizotinib combination)

first: Jiaming

first: Yunying

last: Yao


title: Effect of knockdown USP27 on gene expression of MCF7 cells

city: Weifang

first: Zhenhai

last: Yu

address: No.288 Shengli East Street

institute: Weifang Medical University

summary: To investigate USP27 in tumorigenesis, we established cell lines in which target gene has been knocked down by shRNA.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for cells and its KD derivatives (shUSP27).


title: FBXO45, a new guardian of the genome

first: Lian

last: Li

state: Shanghai

address: No.1158, Gongyuan East Road, Shanghai

department: Department of Respiratory and Critical Care Medicine

institute: QingPu Branch of Zhongshan Hospital Affiliated to Fudan University

summary:
Conditional knockout of Fbxo45 in alveolar epithelial type II cells (AT2) in mice (cKO) resulted in spontaneous lung adenocarcinoma.
To investigate why deletion of Fbxo45 in AT2 leads to lung adenocarcinoma.
We isolated primary AT2 cells from 6-month-old WT, cKO mice for high-throughput RNA-sequencing analysis. (WT=2, cKO=2)

overall_design: Comparative gene expression profiling analysis of RNA-seq data for WT-AT2 cells and KO-AT2 cells.

first: Jianxiu


title: Effect of A4368 compound on global gene expression in Hep3B cells

city: Incheon

first: Kwang Won

last: Jeong

address: 191 Hambakmoe-ro, Yeonsu-gu

department: College of Pharmacy

institute: Gachon University

summary: We performed transcriptome analysis in A4368-treated cells to investigate the effect A4368 on genome-wide expression in Hep3B cells.

overall_design: Differential expresssion profile of transcripts A4368-treated Hep3B cells.

first: Mingli

last: Jin

first: Kwang

middle: W


title: Single-cell transcriptomic analysis reveals transcriptional and cell subpopulation differences between human and pig immune cells

city: Beijing

first: Zhaoqi

state: Beijing

address: Beijing China Institute of Zoology，Chinese Academy of Sciences

institute: University of Chinese Academy of Sciences

summary: The pig is a promising candidate for xenotransplantation. Understanding the differences between human and swine immune systems is critical for addressing xeno-transplant rejection and hematopoietic reconstitution. We performed single-cell RNA-seq on human and pig immune cells. High oxidative phosphorylation, HIF-1, glycolysis, and lysosome-related gene expressions in pig CD14+ monocytes were observed, whereas pig CD14+ monocytes exhibited lower levels of cytokine receptors and JAK-STAT-related genes. Pig activated CD4+T cells decreased cell adhesion and inflammation, while enriched for migration and activation processes. Porcine GNLY+CD8+T cells reduced cytotoxicity and increased proliferation compared with human GNLY+CD8+T cells. Pig CD2+CD8+γδT cells were functionally homologous to human CD2+CD4+ γδT cells. Pig CD2-CD8-γδT cells expressed genes with quiescent and precursor characteristics, while CD2-CD8+γδT cells expressed migration and memory-related molecules. Pig CD24+ and CD5+B cells are associated with inflammatory responses. Our research with integrated scRNA-seq enables a deeper understanding of the development and function of porcine immune cells.

sample_organism:
Homo sapiens
Sus scrofa

platform_organism:
Homo sapiens
Sus scrofa

overall_design: Pig blood was collected from the anterior vena cava, and human blood was collected from the median cubital vein. PBMCs were isolated by Ficoll gradient centrifugation.


title: RNA-seq of depletion Mina53 in HCT116 p53+/+ cells and HCT116 p53-/- cells

first: Lixiao

last: Zhou

address: Yuhangtang road

institute: Zhejiang University

summary: We report the signaling pathway of Mina53 by depleting Mina53 in HCT116 p53+/+ cells and HCT116 p53-/- cells based on RNA-sequencing.

overall_design: By using magnetic oligo(dT) beads to enrich the total RNA with poly A, and then breaking the RNA to fragments about 300bp, these fragments are used as models to get cDNA by using primers and reverse transcriptase, and then the second cDNA model. After the library was constructed, we use next-generation sequencing (NGS) based on Illumina HiSeq sequencing platform to detect the DNA sequence. After filtrating the raw data, the clean data was blast to the human genome sequence.

first: Wen

last: Yi


title: Time-dependent expression data from human fibrosarcoma human cell line (HT1080) in collagen matrix with protease inhibitors

city: London

first: Oscar

last: Maiques

address: Charterhouse Square

department: Tumour Microenvironment

country: United Kingdom

institute: Queen Mary's University of London- Cancer Research UK Barts Centre

summary: HT1080 cells were grown on collagen I and treated with PI for 4 h (short term) and 24 h (long term) while RNA was extracted for Genome-wide Affymetrix Microarray gene expression analysis. The objective of this study was to identify whether collagen accumulation driven by blocking proteases induced transcriptional changes that correlated sustained amoeboid cell state.

overall_design: 9 samples (3 x 3 biological replicates). Cells were plated on deformable matrices. Human fibrosarcoma cells (HT1080 cells) plated on deformable matrices were left untreated or treated with proteinase kinase inhibitor cocktail.

first: O

first: V

last: Sanz-Moreno


title: Characterization of DNA methylation changes associated with lung and right ventricle dysfunction in pulmonary hypertension

city: Spring House

first: Vinod

last: Krishna

state: Pennsylvania

address: 1400 McKean Road

institute: Janssen R&D LLC

summary: Pulmonary arterial hypertension (PAH) is a lethal vasculopathy associated with pulmonary arteries remodeling and right ventricle (RV) dysfunction. Epigenetic dysregulation, including altered DNA methylation, promotes PAH. However, the DNA methylation changes associated with PAH and their functional consequences on transcriptomic reprogramming remain unexplored in human PAH RV and lungs. We conducted an exploratory study in human lung and RV samples to characterize the DNA methylome and transcriptomic changes associated with PAH in both organs. Impaired DNA methylation landscape observed in PAH lungs and RV correlates with adverse pulmonary vascular remodeling, RV fibrosis, and markers of disease severity (e.g. NT-proBNP). PAH differentially methylated genes and differentially expressed transcripts regulate biological functions related to inflammation, fibrosis, heart contraction, blood vessel development. Moreover, we observed substantial lung/RV transcriptomic and methylomic changes overlap in PAH. Thus, PAH is associated with specific DNA methylation changes associated with the disease severity.

overall_design: mRNA profiles for control and PAH human right ventricle and lung

first: Francois

last: Potus

first: Reem

middle: E

last: Kabbout


title: METTL3 regulates chromatin of human trophoblasts

city: Wuhan

first: Hanyang

last: Hu

state: Please Select

address: School of Basic Medical Sciences, Wuhan University

institute: Wuhan University

type: Genome binding/occupancy profiling by high throughput sequencing

summary: To investigate the role of METTL3-mediated chromatin dynamics, we performed ChIP-seq for METTL3, ARID1A and H3K27ac,and ATAC-seq in high glucose treated control or METTL3 knockdown HTR8/SVneo cells.

overall_design: METTL3, ARID1A and H3K27ac ChIP-seq and ATAC-seq of the METTL3 knockdown and control HTR8/SVneo cells with treatment of 30 mM glucose for 24 hours

first: Lulu

last: Ji


title: hPSC-Derived Enteric Ganglioids Model Human ENS Development and Function [scRNA-seq]

city: San Francisco

first: Faranak

last: Fattahi

state: California

department: Cellular and Molecular Pharmacology

institute: University of California San Francisco

summary: We used single cell RNA sequencing (scRNA-seq) for molecular characterization of our hPSC-derived enteric crestosphere and 2D enteric nervous system models

overall_design: For each sample we pooled cells from two independent biological repeats.

first: Ryan

last: Samuel

first: Andrew

last: Cesiulis

first: Kevin

last: Barber

first: Matvei

last: Khoroshkin

first: Johnny

first: Hani

last: Goodarzi

first: Homa

last: Majd


title: ABCA1-eRNA as a novel Epigenetic Regulator, promotes cholesterol efflux, Attenuates Macrophage Inflammation and Severity of Coronary Artery Disease [ABCA1 RNA-seq]

city: WuHan

first: shuai

last: mei

address: 1095# Jiefang Ave

summary: Enhancer RNAs (eRNAs) are emerging as powerful regulators of various biological processes, but the underlying epigenetic regulatory mechanisms of these molecules in cholesterol homeostasis remain elusive. Using an integrated genomic screen, we identified an intragenic super-enhancer derived long noncoding RNA embedded in the ATP-binding cassette transporter A1 (ABCA1) gene, named ABCA1-seRNA, which is required for activation of RXRα/LXR mediated gene expression. Deficiency of ABCA1-seRNA abolished cholesterol efflux, promotes Macrophage Inflammation, and that haven been causally Susceptibility to Coronary heart disease. Mechanistically, ABCA1-seRNA affects cholesterol efflux by interaction with MED23 and recruitment RXR and LXR to mediate ABCA1 transcription in cis. Furthermore, ABCA1-seRNA repression inflammatory response and attenuated macrophage M1 polarization and migration through ubiquitination of a NF-B subunit P65. Our results suggest that super-enhancer derived long noncoding RNA, as a novel Epigenetic Regulator, are critical components to maintain cholesterol homeostasis and inflammation restriction, represent an attractive therapeutic target to reduce Atherosclerotic cardiovascular disease (ASCVD).

overall_design: THP1 mRNA profiling of RNAi-Ctrl or RNAi-ABCA1-seRNA

first: Dao

last: Wang

first: Hu

last: Ding


title: ABCA1-eRNA as a novel Epigenetic Regulator, promotes cholesterol efflux, Attenuates Macrophage Inflammation and Severity of Coronary Artery Disease [MED23 RNA-seq]

overall_design: THP1 mRNA profiling of si-NC and si-MED23


title: ABCA1-eRNA as a novel Epigenetic Regulator, promotes cholesterol efflux, Attenuates Macrophage Inflammation and Severity of Coronary Artery Disease

summary: This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series


title: hPSC-Derived Enteric Ganglioids Model Human ENS Development and Function [snRNA-seq]

summary: We used single nuclei RNA sequencing (snRNA-seq) for molecular characterization of our hPSC-derived enteric nervous system models termed enteric ganglioids.

overall_design: For each sample we pooled ganglioids from an independent differentiation and for each condition we used two independet samples.

first: Jonathan

last: Ramirez


title: ABCA1-eRNA as a novel Epigenetic Regulator, promotes cholesterol efflux, Attenuates Macrophage Inflammation and Severity of Coronary Artery Disease [ATAC-seq]

overall_design: the choromatin accessibility profiling of RNAi-Ctrl or RNAi-ABCA1-seRNA THP-1 cells


title: Binding sites and the core motif of CmNOR.

first: Yongtao

last: Yu

address: 50 Zhanghua

institute: Beijing Academy of Agriculture and Forestry Sciences

summary: We used DAP-seq technology to identify the binding sites and the core motif of CmNOR.

overall_design: We set two negative controls and two experimental groups

first: Jinfang

first: Yong

last: Xu


title: ABCA1-eRNA as a novel Epigenetic Regulator, promotes cholesterol efflux, Attenuates Macrophage Inflammation and Severity of Coronary Artery Disease [CUT&TAG]

overall_design: the Cleavage Under Targets and Tagmentation (CUT&Tag) profiling of RNAi-Ctrl or RNAi-ABCA1-seRNA THP-1 cells


title: CXCR3-expressing macrophages regulate angiogenesis, tumor cell proliferation and immune evasion in hepatocellular carcinoma

city: Aachen

first: Zhijian

last: Li

state: North Rhine-Westphal

address: Pauwelsstr. 19

country: Germany

institute: RWTH Aachen University

summary: Chemokine receptor CXCR3 shapes the intrahepatic tumor microenvironment in a highly dynamic manner. Genetic deletion of Cxcr3 has an impact on the development and differentiation of myeloid cells and improves potentially oncogenic properties of tumor-associated macrophages in hepatocellular carcinoma (HCC) bearing mice. This ultimately leads to an increased carcinogenesis.

overall_design: C57BL/6J wild type (WT) and Cxcr3 knockout mice (Cxcr3-/-) were treated with a combination of diethylnitrosamine (DEN) and tetrachloromethane (CCl4) to induce fibrosis-associated HCCs. For functional analysis of CXCR3 during macrophage differentiation a comprehensive in vitro and in vivo analysis was performed. For ATACseq in vitro cultured wild type and Cxcr3-/- common myeloid progenitor cells (CMP)/ granulocyte-monocyte progenitor (GMP) cells and moncytes were used.

first: Elisa

middle: F

last: Brandt

first: Theresa

middle: H

last: Wirtz

first: Mahmoud

last: Ibrahim

first: Petra

last: Fischer

first: Anika

last: Beckers

first: Alexander

last: Flaßhove

first: Antje

last: Mohs

first: Ivan

middle: G

last: Costa

first: Rafael

last: Kramann

first: Emiel

last: van der Vorst

first: Christian

last: Liedtke

first: Hacer

last: Sahin

first: Marie-Luise

last: Berres


title: Genome-wide identification of gamabufotalin (CS-6) targets in MDA-MB-468 cells

city: Changsha

first: Jianlin

last: Zhou

state: Hunan

address: 36 Lushan road

department: College of Life Science

institute: Hunan Normal University

summary: The MDA-MB-468 triplicate-negative breast cancer cells were treated with 18 nmol/L gamabufotalin (CS-6) or DMSO for 24 h. Then, RNA-seq was performed to explore the differentially expressed genes.

overall_design: Comparing the mRNA profilings of MDA-MB-468 cells treated with DMSO or CS-6.

first: Liqin

last: Yuan

first: Meiling


title: Blocking DCIR mitigates colitis and prevents colorectal tumors by enhancing the GM-CSF-STAT5 pathway

city: Noda

first: HAIYANG

last: SUN

state: Chiba

address: Yamazaki

country: Japan

institute: Research Institute for Biomedical Sciences,  Tokyo University of Science

summary: Dendritic cell immunoreceptor (DCIR; gene: Clec4a2), a member of the C-type lectin receptor family, plays important roles in homeostasis of the immune and bone systems. However, the intestinal role of this molecule is unclear. Here, we showed that the severity of dextran sodium sulfate (DSS)–induced colitis and the incidence of azoxymethane-DSS–induced intestinal tumors was reduced in Clec4a2–/– mice in an intestinal microbiota–independent manner. STAT5 phosphorylation and expression of Csf2 and tight junction genes were enhanced, while expression of Il17a and Cxcl2 was suppressed in the Clec4a2–/– mouse, which exhibited reduced infiltration of neutrophils and myeloid-derived suppressor cells. GM-CSF administration ameliorated DSS colitis associated with reduced Il17a and enhanced tight junction gene expression, whereas anti–GM-CSF significantly exacerbated the symptoms. Furthermore, blocking the ligand-DCIR interaction ameliorated colitis and prevented colorectal tumors. These observations indicate that blocking DCIR signaling ameliorate colitis and suppresses colonic tumors, suggesting DCIR as a possible target for the treatment of these diseases.

overall_design: Colon mRNA profiles of wild type (WT) and DCIR–/–  mice. Samples were collected 1) in steady state, 2) on day 12 after DSS induction, 3) on day 112 after AOM-DSS induction. Totally five samples of colon, one biological replicate fo each one, were analyzed.

first: Haiyang

last: Sun

first: Xiao-Qi

last: Ye

first: Ce

last: Tang

first: Yoichiro

last: Iwakura


title: Activation of CASP1 induces AML cell pyroptosis and sensitizes to ATRA treatment

city: Guangzhou

first: xibao

last: yu

state: Guangdong

address: No.601, West Huangpu Avenue

department: Department of Hematology

institute: Jinan University

summary: Acute myeloid leukemia (AML) is characterized by the accumulation of immature leukemic blasts. The application of all-trans retinoic acid (ATRA) treatments have markedly transformed acute promyelocytic leukemia (APL, the M3 subtype of AML) to a highly manageable disease, and research strategies that seek to extend the application of ATRA-based treatment to other AML subtypes are an important area of investigation. Here, we found CASP1/GSDMD was lower expressed in APL and most other subtypes of primary de novo AML patients and increased in ATRA-treated APL cells. We showed that ATRA increased and activated CASP1 to trigger pyroptosis and differentiation of APL cells. Mechanistically, ATRA could induce CASP1 expression via IFNγ/STAT1 in APL and non-APL AML cells, while do not activate CASP1 in non-APL AML cells. Accordingly, pharmacological activation of CASP1 by Val-boroPro (DPP8/9 inhibitor) enhanced pyroptosis and differentiation induced by ATRA in AML cells. Moreover, the combination of ATRA and Val-boroPro enhanced anti-leukemia activity in primary AML cells. Our study demonstrates that the ATRA-mediated anti-leukemia effect requires a functional activated CASP1 and provides a highly attractive therapeutic strategy for the treatment of AML.

overall_design: Gene expression analysis of DMSO, single and combination treatment (ATRA and VbP) on AML cell lines HEL and KG1a

first: Xibao

last: Yu

first: Zhuandi

last: Liu

first: Dingrui

last: Nie

first: Cunte

last: Chen

first: Xiangbo

last: Zeng

first: Youxue

last: Huang

first: Xin

first: Mengjun

last: Zhong

first: Xianfeng

last: Wang

first: Songnan

last: Sui

first: Gengxin

last: Luo

first: Ling

last: Xu

first: Yangqiu

last: Li

first: Chengwu


title: Transcriptomes of Wild Type tomato and sllbd40 fruit on different fruit stages

first: Lun

address: No. 2, Yuanmingyuan West Road, Haidian District, Beijing

institute: China Agricultural University

summary: In order to find the gene which were regulated by SlLBD40, the fruits of WT and SlLBD40-KO-5 line were collected at 25 DDA to do the RNA-Seq. Total RNA was extracted from above tomato fruits by TRIzol reagent and three biological replicates were taken. The clean data were aligned to the tomato reference genome release SL2.50. According to the RNA-Seq data, many development-related genes were down-regulated in SlLBD40-KO-5 fruit. We find the potential SlLBD40-regulated genes.

overall_design: Fruit mRNA profiles of 25 DAA fruits of wild type (Micro Tom) and  sllbd40 mutant

first: Jialong

last: Zhang

first: Yang-Dong

last: Guo


title: Integration between MCL1 gene co-expression module and the Revised International Staging System enables precise prognostication and prediction of response to proteasome inhibitor-based therapy in individual multiple myeloma

first: Yin

last: Wu

state: -- select

address: No. 8 Gongti south street road, Chaoyang district

department: Heamotologic department

institute: Capital Medical University Beijing Chaoyang Hospital

summary:
We recently identified a gene module of 87 genes co-expressed with MCL1 (MCL1-M), a critical regulator of plasma cell survival. MCL1-M captures both MM cell-intrinsically acting signals and the signals regulating the interaction between MM cells with bone marrow microenvironment. MM can be clustered into MCL1-M high and MCL1-M low subtypes. While the MCL1-M high MMs are enriched in a preplasmablast signature, the MCL1-M low MMs are enriched in B cell-specific genes. In multiple independent datasets, MCL1-M high MMs exhibited poorer prognosis compared to MCL1-M low MMs. Re-analysis of the phase III HOVON-65/GMMG-HD4 showed that only MCL1-M MMs, but not MCL1-M low MMs, benefited from bortezomib-based treatment. To translate the MCL1-M clustering scheme into a platform for individual diagnosis, we refined the classifier genes and developed a support vector machine-based algorithm.
Individual MMs with transcriptome assessed at the RNA-seq or U133 plus 2.0 array platform can be robustly assigned as the MCL1-M high or low subtype with high confidence. Analyses of the MM samples in the HOVON-65/GMMG-HD4 trial and APEX trial reinforce that only MCL1-M high MMs benefit from bortezomib-based treatment with a hazard ratio of 0.58 (P = 0.010) and 0.47 (P = 0.009), respectively. Thus, MCL1-M based subtyping assigns MMs into prognostic and predictive molecular subtypes driven by subtype-specific pathogenic pathways.

overall_design: We also generated our own data set based on 72 newly diagnosed MM samples  from Chaoyang hospital in Beijing. All participants signed the informed consent form, and the study was approved by the institutional ethical review board of the Chao-Yang Hospital, Capital Medical University (Beijing, China). Patients were treated between August 2015 and September 2019, the longest follow-up period was 67 months. Bone marrow CD138+ cells were purified for the preparation of total mRNA for the transcriptome profiling using Affymetrix PrimeView array according to standard protocols.


title: Transcriptome analysis of mouse follicular (FO) and marginal zone (MZ) B cells from control mice and of MZ B cells from mice overexpressing AKT-1 in B cells

city: Jouy-en-Josas

first: Jouneau

last: Luc

address: Domaine de Vilvert

country: France

institute: INRA

summary: The purpose of this experiment is to delineate whether Akt over-expression is sufficient to induce a marginal zone-like phenotype in B cells at the molecular level. Mice expressing constitutively Akt in B cells have almost only marginal zone B cells in secondary lymphoid organs, as much as we can say through characterization of cell surface receptor by flow cytometry. These analyses were conducted in order to gain a more precise understanding of the relationship between WT marginal zone B cells and marginal zone B cells produced as a result of constitutive Akt signalling.

overall_design: The experiments include a total of 9 arrays, each corresponding to a distinct biological sample. There are 3 arrays (3 samples) for FO B cells from control mice (Cd19-cre mice; Rickert et al. 1997), 3 arrays for MZ B cells from the same control mice, and 3 arrays from mice expressing an hyperactive AKT-1 in B cells (AKTboe mice that are Cd19-cre x ROSA26-LoxP-STOP-LoxP-AKT1-ires eGFP; see PMID: 33140819 for the description of this allele)

first: Simon

last: Fillatreau

first: Nadine

last: Hövelmeyer

first: Luc

last: Jouneau


title: Ablation of the Sost gene prevents hallmarks of calcific aortic valve disease in a high-cholesterol mouse model

city: Nashville

first: Lance

last: Riley

state: TN

address: 9445 MRB4, 2213 Garland Ave

department: Biomedical Engineering

institute: Vanderbilt University

summary: The purpose of this study was to understand the effect of sclerostin genetic ablation (gene: Sost) on aortic valve fibrocalcification in an aged, high-cholesterol diet mouse model. Sclerostin is a potent agent in bone remodeling. It both blocks Wnt-mediated osteoblast bone deposition and spurs RANKL-mediated osteoclast maturation and subsequent bone resorption. A monoclonal antibody was recently approved as a treatment for post-menopausal osteoporosis but clinical trials indicated potential cardiovascular side effects. This study aimed to begin to understand the potential role of sclerostin in the aortic valve.

overall_design: C57BL6/J background mice with wild-type or double knockout  of the Sost gene were aged to 4 months on standard chow and then transferred to high-cholesterol diet for 8 months. Aortic roots were harvested at one-year of age. N=3 aortic roots from each experimental group were used for this RNA sequencing analysis.

first: Jeffrey

last: Joll

middle: A

first: W

middle: D

last: Merryman


title: RNA-seq for HCT116 cells with TTC22-OE or kockdown

city: BEIJING

first: WEI

last: TIAN

address: FUCHENG ROAD 52#

institute: BEIJING CANCER HOSPITAL

summary:
object:compare the genes influenced by TTC22 overexpression or knockdown
Methods: For whole-genome transcriptome profiling, four libraries were generated from total RNA samples extracted from Flag-TTC22-OE, empty vector control, scramble RNA control, and TTC22-KD (siTTC#1&2&3) HCT116 cells using TruSeq® RNA Sample Preparation Kit (Illumina Inc.) according to the manufacturer’s protocol, and sequenced on the Illumina HiSeq PE150 platform (Genminix, Shanghai, China) using the 150–base pair single-end sequencing module. Hisat2 (version:2.0.4) was used to map the cleaned reads to the human hg38 reference genome.
Results: The mRNA data obtained from transcriptome sequencing, subjected to T-test statistics and corrected by the RVM model. Significant differential mRNA (TwoClassDif) between TTC22-OE and vector control cells or between TTC22-KD and scramble RNA control cells was yielded. Up-regulated and down-regulated genes (fold change>1.5, calculated through Ballgown algorithm) were performed to find significant functions and significant signaling pathways based on the Gene Ontology database (GO-Analysis) or KEGG database.(Pathway-Analysis).
Conclusion:The results suggested that TTC22 could affect the RNA metabolism pathway that controls the progression and metastasis of CC.

overall_design: mRNA profiles of TTC22 overexpression or knockdown in colon cancer HCT116 cells

first: Wei

last: Tian

first: Dajun

last: Deng


title: Folic acid intake during juvenile/peri-pubertal development modulates the mammary tissue transcriptome of female C56BL/6 mice

city: Oxford

first: Elie

last: Antoun

state: United Kingdom

address: Nuffield Department of Medicine

department: CAMS China Oxford Institute (CAMS-COI

institute: University of Oxford

summary:
We tested the hypothesis that high FA (HFA) intake alters the juvenile/peri-pubertal mammary transcriptome in a manner consistent with increased potential for breast cancer, detectable beyond the period of intake. C57BL/6 mice were fed control FA (CFA) (1 mg/kg diet) or HFA (5 mg/kg diet) diets for 4 weeks, followed by AIN93M maintenance diet for 4 weeks.
RNA sequencing of the mammary transcriptome (~83 million reads) showed 18 transcripts (17 downregulated) differentially expressed between groups. Gene Set Enrichment showed downregulated genes significantly enriched in oxidative phosphorylation, adipogenesis, fatty acid metabolism and epithelial mesenchymal transition. Cancer and developmental disorder were the most altered Disease and Disorder pathways, with top upstream regulators identified as DNA methyltransferases.
This study demonstrates HFA intake during juvenile/peri-pubertal mammary development induces changes in the mammary transcriptome associated with altered energy metabolism, cell neoplasia and epigenetic regulation of gene.

overall_design: C57BL/6 PND84 Mammary gland RNA transcriptomes 4 weeks after a follic acid supplemntation (5mg/kg or 1mg/kg).


title: Shear stress-induced long non-coding RNA, NIMBUSS, is required for the KLF2-mediated gene expression profile associated with vascular homeostasis I

city: Toronto

first: Philip

last: Marsden

state: ON

address: 209 Victoria Street, Room 522

department: Medicine

country: Canada

institute: University of Toronto

type:
Expression profiling by array
Non-coding RNA profiling by array

summary: The endothelial cell (EC) response to shear stress is partly mediated by the transcription factor KLF2, which is preferentially activated by laminar flow and promotes an atheroprotective phenotype. The up-regulation of KLF2 elicits anti-inflammmatory, anti-coagulant, and pro-vasodilatory processes. To investigate the function of the flow-induced long non-coding RNA (lncRNA) NIMBUSS, we performed loss-of-function studies using siRNA for NIMBUSS in ECs overexpressing KLF2.

overall_design: Four independent human umbilical vein endothelial cells (HUVEC) lines were transduced with adenovirus overexpressing GFP only or murine KLF2, and transfected with either control or two independent NIMBUSS siRNAs (16 samples: 8 Ad-GFP, 8 Ad-KLF2). Total RNA was isolated and analyzed using the Human lncRNA Microarray V3.0 (Arraystar) which profiles the expression of 30,586 lncRNAs and 26,109 protein-coding genes.

first: Aravin

middle: N

last: Sukumar


title: RNA sequencing of lung tissue of cynomolgus monkeys

first: Zunpeng

last: Liu

address: Beichen West Road

department: Institute of Zoology, Chinese Academy of Sciences

institute: State Key Laboratory of Stem Cell and Reproductive Biology

summary: RNA sequencing of lung tissue of young/old male/female cynomolgus monkeys

overall_design: RNA sequencing of lung tissue of young and old cynomolgus monkeys.

first: Guanghui


title: Resistance of Norway spruce tree clones  against the root and stem rot conifer pathogen (Heterobasidion parviporum)

city: Helsinki

first: Fred

last: Asiegbu

address: Latokartanonkaari 7

country: Finland

institute: University of Helsinki

summary: By exploring the large-scale transcriptome analysis, we aim to identify differentially expressed genes in the comparison betweem tolerant and susceptible clones.

overall_design: mRNA profiles of needles from tolerant and susceptible 3-year old Norway spruce clones

first: Mengxia

first: Kai

last: Wang


title: Shear stress-induced long non-coding RNA, NIMBUSS, is required for the KLF2-mediated gene expression profile associated with vascular homeostasis II

summary: To investigate the regulation of the long non-coding RNA (lncRNA) transcriptome of endothelial cells in response to shear stress, gene expression profiling was performed using a microarray for both protein-coding genes and lncRNAs. The expression of known flow-induced protein coding genes, eNOS, KLF2, and KLF4, were quantified using real-time PCR. Identifying lncRNAs that are up-regulated or down-regulated in the presence or absence of laminar flow will provide insight into gene regulatory mechanisms that contribute to vascular homeostasis or disease.

overall_design: Five independent human umbilical vein endothelial cells (HUVEC) lines were subjected to either static or non-pulsatile, laminar flow (10 dynes/cm2, 48 hours) and total RNA was isolated. RNA was analyzed using the human lncRNA expression microarray V3.0 (Arraystar) which profiles the expression of 30,586 lncRNAs and 26,109 protein-coding genes. Total 10 samples: 5 static and 5 flow samples.


title: T cell receptor-induced alternative splicing of MALT1 affects T cell signaling and effector cell differentiation

city: Neuherberg

first: Martin

last: Irmler

state: Bayern

address: Ingolstaedter Landstrasse 1

department: Institute of Experimental Genetics

institute: Helmholtz Zentrum München GmbH

summary: MALT1 is an essential component of the T cell receptor (TCR)-induced T cell activation pathway. Two alternative splice isoforms of MALT1 (ISO A and ISO B) are conserved within vertebrae, which differ in the presence of exon 7 (MALT1 ISO A). We show by isoform-specific reconstitution of MALT1-deficient CD4-positive T cells that MALT1 ISO A mediates additional functions in T cell activation. Transcriptome-wide analysis revealed a distinct subset of genes specifically upregulated in presence of exon 7.

overall_design: Total RNA from sorted T cell was obtained from 4 animals, unstimulated, stimulated, mock stimulated (reference)

first: Johannes

last: Beckers

first: Marion

last: Horsch


title: Gene expression analysis of liver and heart from wildtype and ABCB5 mutant mice

summary: Abcb5 is a member of the ATP-Binding Cassette (ABC) transporter superfamily. It is an energy dependent transporter and its role is unknown yet. We are characterizing this transporter at the genomic and protein level. We know that it is highly expressed in pigmented cells, including pigmented cells of the CNS (retinal pigment epithelium and basal ganglion cells). We found it highly expressed in melanotic melanoma and in alveolar soft part sarcoma.

overall_design: Total RNA obtained from liver and heart of 3-4 male homozygous ABCB5 mutant and 4 male wildtype mice


title: Single cell gene expression profiling of splenic cells in mice treated with gated CD33-CD123 CARs compared to those with conventional CD123 CAR expression

status: Public on Nov 29 2024

city: Los Angeles

first: Babak

last: Moghimi

state: CA

address: 4650 sunset blvd

institute: CHLA

summary: Single-cell profiling of specific cells in humanized mice treated with gated and conventional CAR-T cells, illustrating the mechanisms of Cytokine Release Syndrome (CRS) and cross-talk between human and mouse cells in animals presenting with CAR-induced CRS symptoms.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Humanized SGM3 mice, generated from human CD34+ cells, were evaluated for evidence of engraftment and subsequently inoculated with MOLM-13 AML cells. Following this, a 10-million dose of CAR-T cells (both gated and constitutively expressed) was administered. Mice were monitored weekly, and as symptoms of Cytokine Release Syndrome (CRS) developed and animals reached study endpoints, splenic cells were isolated. These cells were then subjected to single-cell analysis after enrichment for mouse and human CD45+ cells, with the enriched cells added back at a 1:1 ratio.

first: Jambon

last: Samy

first: Sun

last: Jianping

first: Barman

last: Shawn

first: Muthugounder

last: Sakunthala

first: Bito

last: Rachel

first: Shadfar

last: Armita

first: Kovach

last: Alexandra

first: Wood

last: Brent

first: Manoharan

last: Thoppey

first: Morrissy

last: Sorana

first: Bhojwani

last: Deepa

first: Wayne

last: Alan

first: Pulsipher

last: Michael

first: Kim

last: Yong-Mi

first: Asgharzadeh

last: Shahab

first: Parekh

last: Chintan

first: Moghimi

last: Babak


title: Pharmaceutical reversal of Dkk1-induced LRP6 endocytosis prevents cancer cachexia and prolongs survival

city: shanghai

first: meng

last: liu

address: 1239,SiPing Road

institute: TongJi University

summary: Cancer cachexia with profound weight loss and frailty impairs quality of life, limits cancer therapy and decreases survival, against which no effective therapy is available. Dkk1 is a secreted antagonist of Wnt/β-catenin pathway via interacting with Wnt co-receptors LRP5 and 6 (LRP5/6) and inducing their endocytosis1-4.  Although Dkk1 is critical for animal development3,5, its mRNA is undetectable in most adult organs6. Of note, elevated circulating Dkk1 leads to poor prognosis in patients with a variety of types of cancer by a completely unknown mechanism. Here, we show that administration of a recombinant Dkk1 protein accelerated cancer cachexia-related death through inducing LRP6 endocytosis but not β-catenin inhibition, whereas pharmacological blockade of Dkk1-induced membrane LRP6 downregulation completely prevented cancer cachexia and robustly prolonged survival in tumor-bearing mice. Pharmacological blockade of Dkk1-induced membrane LRP6 downregulation prevented alterations of a number of GPCR pathways and all main cancer cachexia-related pathways in skeletal muscle of mice bearing tumor as shown by a genome-wide transcriptional analysis. Furthermore, Dkk1 injection into hindlimb directly triggered activations of GPCR pathways and cachexia-related pathways. These findings establish a key role of the Dkk1-LRP6 axis in cancer cachexia development through affecting GPCR pathways and suggest a highly promising therapeutic approach for preventing cancer cachexia.

overall_design: We collected muscle cellls and/or kidney cells from mouse of different conditions respectively and conducted RNA-seq.

first: Weidong

last: Zhu


title: Deep conservation of cis-regulatory elements and chromatin organization in echinoderms uncover ancestral regulatory features of animal genomes [Hi-C]

status: Public on Nov 30 2024

city: Seville

first: Marta

middle: Silvia

last: Magri

address: Carretera de Utrera km1

country: Spain

institute: Centro Andaluz de Biología del Desarrollo

summary: we generated new reference genome assemblies for two species belonging to two different echinoderm classes: the bat sea star Patiria miniata and  the purple sea urchin Strongylocentrotus purpuratus

sample_organism:
Strongylocentrotus purpuratus
Patiria miniata

overall_design: Hi-C assays in wild-type sea star and sea urchin whole embryos at late gastrula

first: Marta Silvia

first: Danila

last: Voronov

first: Saoirse

last: Foley

first: Pedro Manuel

last: Martínez-García

first: Martin

last: Franke

first: Gregory A

last: Cary

first: José M

last: Santos-Pereira

first: Carolyn

last: Ku

first: Claudia

last: Cuomo

first: Manuel

last: Fernández-Moreno

first: Alejandro

last: Gil-Galvez

first: Rafael D

last: Acemel

first: Periklis

last: Paganos

first: Jovana

last: Ranđelović

first: Maria Lorenza

last: Rusciano

first: Panos N

last: Firbas

first: Veronica F

last: Hinman

first: Maria Ina

last: Arnone

first: Ignacio

last: Maeso

first: José

middle: L

last: Gómez-Skarmeta


title: Yeast Thigmotropism Controlled by a Cell-Surface Mucin and a MAP-Kinase Pathway

city: Bar Harbor

first: Gregory

last: Carter

state: ME

address: 600 Main Street

institute: The Jackson Laboratory

summary: Budding yeast can switch from growth as ovoid cells to growth in an adhesive and invasive filamentous form.  Limiting availability of reduced nitrogen is thought to be the signal that induces filamentous growth.  In contrast, we find that filamentation is a thigmotropic response.  In the absence of repressive agents, growth on a surface is necessary and sufficient to induce filamentation, whereas nitrogen limitation is neither sufficient nor necessary.  The thigmostimulus is transmitted to the genome via a MAP-kinase pathway that has been linked to filamentation.  The FLO11 gene, encoding a cell-surface mucin protein, maps genetically at the top and at the bottom of this thigmotropism MAP-kinase pathway.  These results suggest that yeast differentiation to the filamentous form is primarily a response to surface contact for the purposes of colonization and invasion, rather than foraging for nutrients.

platform_organism:
Schizosaccharomyces pombe
Saccharomyces cerevisiae

overall_design: Gene expression was assayed for yeast cells grown in liquid cultures and on solid substrates with various nutrient compositions.  Samples were collected from wild-type and strains harboring mutations of a proposed thigmotropism MAP-kinase pathway to identify the genomic response to thigmostimuli (touch).

first: Song

last: Li

first: Susanne

last: Prinz

first: Timothy

last: Galitski


title: Deep conservation of cis-regulatory elements and chromatin organization in echinoderms uncover ancestral regulatory features of animal genomes

first: Marta

last: Magri

summary: This SuperSeries is composed of the SubSeries listed below.

platform_organism:
Strongylocentrotus purpuratus
Patiria miniata

overall_design: Refer to individual Series


title: CosMx 6175 human gene for human kidney primary non-function and immediate graft function.

city: Sacramento

first: Yongheng

last: Wang

address: 3101 Clinical Lab Building (Research II), UC Davis Medical Center, 4625 2nd Ave.

institute: University of California Davis

summary: This dataset includes CosMx spatial transcriptomic data from human kidney biopsies collected one hour post-transplantation. Patients were then monitored and categorized into two groups: immediate graft function (IGF) and primary nonfunction (PNF). PNF refers to cases where the transplanted kidney never functions. The biopsies were formalin-fixed, paraffin-embedded, and sectioned using a microtome. Sample processing followed NanoString's standard protocol, utilizing a pre-made 6,175-gene panel to detect the spatial location and expression levels of each gene, without any additional custom probes.

overall_design: This study contains human kidney biopsies form 2 groups: immediate graft function (IGF) and those with delayed graft function (PNF).

first: Siyu

last: Lin

first: Weidi

last: Zhang

first: Kuang-Yu

last: Jen

first: Peter

last: Than

first: Aijun


title: STING facilitates vascular calcification via p-STAT1/NLRP3 signal

status: Public on Nov 28 2024

first: Xiaoyu

last: Liu

address: 253 Industrial Avenue, Guangzhou, 510280, China

department: Department of Cardiology

institute: Zhujiang Hospital, Southern Medical University

summary: Vascular calcification contributes to the cardiovascular morbidity and mortality of chronic kidney disease (CKD), but there is no approved treatment for vascular calcification. In this study, we report the role of STING in vascular calcification. To further investigate the molecular mechanism by which STING participates in vascular calcification, we performed high-throughput RNA-seq to identify the target gene of STING.

overall_design: Primary mouse vascular smooth muscle cells from wild type and STING-/- mice were cultured in calcifying medium (CM). RNA-seq was performed to determine the downstream target of STING.

first: Jianyun

last: Yan

first: Lihe

last: Lu


title: CG1603 regulation of nuclear-encoded mitochondrial gene expression

status: Public on Nov 27 2024

city: Bethesda

first: Fan

address: 10 Center Dr.

institute: NHLBI

summary: Through a genetic screen in Drosophila melanogaster, CG1603 was identified as one of the transcription factors that coordinate mitochondrial biogenesis. To investigate the role of CG1603 in regulating nuclear-encoded mitochondrial gene expression, we collected second-instar larvae from wild type and CG1603PBac mutants (a mutant allele that disrupts the translation of the full-length CG1603 protein). We purified mRNA from the samples in triplicate and compared the mRNA transcriptome profiles (RNA-seq). We found that, between wild-type and CG1603PBac larvae, more than 80% of nuclear-encoded mitochondrial genes were differentially expressed. Nearly half of the nuclear-encoded mitochondrial genes were reduced by more than twofold in CG1603PBac mutants, including many structural subunit genes of all five ETC complexes. Gene Ontology (GO) enrichment analysis of the significantly downregulated genes also revealed that the most significantly enriched biological processes were related to mitochondria, including “mitochondrial translation,” “mitochondrial gene expression,” “electron transport chain,” “aerobic respiration,” and “ATP metabolic process.” These results suggest that CG1603 is essential for nuclear mitochondrial gene expression.

overall_design: Total mRNAs were extracted from second-instar larvae of wild type and CG1603PBac mutant flies in triplicate. The RNA-seq was performed with Illumina Novaseq 6000.

first: Zhang

last: Fan

first: Xu

last: Hong


title: Transcriptome profiling of vascular fragments 3h and 24h post MCAO in imatinib and PBS treated mice

city: Solna

first: Manuel

last: Zeitelhofer

address: Biomedicum

department: MBB

country: Sweden

institute: Karolinska Institute

summary: We isolated vascular fragments, representing the BBB, from the ipsilateral hemisphere of imatinib and PBS treated mice 3h and 24h post MCAO induction.

overall_design: We analysed the transcriptome of vascular fragments 3h (n=3) and 24h (n=3) post MCAO treated with PBS compared to treated with imatinib 3h (n=2) and 24h (n=3) post MCO induction.


title: Nanostring protein expression of immune cell recruitment and BBB breakdown following Aβ immunotherapy

city: Indianapolis

first: Xavier

last: Taylor

state: Indiana

address: 307 E Merrill St

institute: Eli Lilly and Company

summary: We study immune responses induced by amyloid targeting antibodies and CAA-mediated microhemorrhages using Nanostring Digital Spatial profling in AD mouse models .

overall_design: To compare the protein expression profiles for immune cells surrounding vascular amyloid deposits activated by Fc receptor signaling Ab antibody or isotype control antibody.

first: X

first: N

last: Harun


title: Broad-spectrum tolerance to disinfectant-mediated bacterial killing due to mutation of the PheS aminoacyl tRNA synthetase

city: Xiamen City

first: shouqiang

last: hong

address: No. 4221-117 Xiang'an South Road

institute: Xiamen university

summary: Disinfectants are essential tools for controlling infectious diseases and maintaining sterile conditions in many medical and food-industry settings. Recent work revealed that a deficiency in the PTS carbohydrate phosphor transfer system confers pan-tolerance to killing by diverse disinfectant types through its interaction with the cAMP-CRP regulatory network. The present work characterized a new pan-tolerance mutant obtained by enrichment using phenol as a lethal probe and an Escherichia coli PTS null mutant as a parental strain. The resulting super-pan-tolerant mutant, which harbored an F158C PheS substitution, inhibited bacterial killing by multiple disinfectant classes with surprisingly little effect on antimicrobial lethality. The PheS substitution, which was expected to lower substrate recognition efficiency and result in deacylated tRNAphe occupying the ribosomal A site, activated relA expression and synthesis of ppGpp, even in the absence of disinfectant exposure. ppGpp, along with DksA, increased RpoS function by activating promoters of dsrA and iraP, two genes whose products increase the expression and stability of RpoS. Subsequently, RpoS upregulated the expression of genes encoding a universal stress protein (UspB) and an oxidative stress peroxidase (KatE), which preconditions bacteria to better survive a variety of disinfectants. Disinfectant-mediated accumulation of ROS and bacterial killing were abolished/reduced by an F158C PheS substitution, by exogenous DMSO, and by the PheS F158C substitution up-regulating genes encoding ROS-detoxifying enzymes (katE, sodA, oxyR, ahpC). These data identify a pheS mutation-triggered, ppGpp-stimulated transcriptional regulatory cascade that negates biocide-mediated lethality, thereby tying the stringent response to protection from ROS-mediated biocide lethality.

overall_design: Mid-log-phase cultures of E. coli K-12 were treated with phenol (3.5 mg/mL) for 0 min and 45 min. Cells were collected for total RNA extraction and subsequent RNA-seq. Differential expression of various conditions was analyzed.

first: Shouqiang

first: Miaomiao

last: Chen

first: Xilin

last: Zhao


title: Circadian transcriptome analysis in mouse cultured cortical astrocytes

status: Public on Nov 26 2024

city: Seoul

first: Jae-Hyung

last: Lee

address: 26 Kyungheedae-ro, Dongdaemun-gu

institute: Kyung Hee University

summary: To understand how the circadian clock regulates astrocyte physiology, we conducted a circadian transcriptome analysis in cultured mouse cortical astrocytes

overall_design: After synchronizing the circadian clock of cultured astrocytes by serum shock, cells were collected at intervals of 4 hours, starting from 12hrs post sync to 56hrs post sync. Subsequently, collected cells were subjected to RNA sequencing.

first: Ji

last: Ryu

first: Kyu-Won

last: Shim

first: Hyun

last: Roh

first: Min

middle: S

last: Park

first: Eun

middle: Y

last: Kim


title: The PNUTS phosphatase complex controls transcription pause release

first: Emilia

last: Dimitrova

address: South Parks Road

department: Biochemistry

sample_organism:
Drosophila melanogaster
Homo sapiens
Mus musculus


title: Toll-Like receptor 3-mediated interferon-β production is suppressed by oncostatin m and a broader epithelial-mesenchymal transition program

status: Public on Nov 25 2024

city: Cleveland

first: Noah

middle: Matthew

last: Chernosky

state: Ohio

address: 2103 Cornell Road

department: Pathology

institute: Case Western Reserve University

summary: Background: Patients with Triple Negative Breast Cancer (TNBC) currently lack targeted therapies, and consequently face higher mortality rates when compared to patients with other breast cancer subtypes. The tumor microenvironment (TME) cytokine Oncostatin M (OSM) reprograms TNBC cells to a more stem-like/mesenchymal state, conferring aggressive cancer cell properties such as enhanced migration and invasion, increased tumor-initiating capacity, and intrinsic resistance to the current standards of care. In contrast to OSM, Interferon-β (IFN-β) promotes a more differentiated, epithelial cell phenotype in addition to its role as an activator of anti-tumor immunity. Importantly, OSM suppresses the production of IFN-β, although the mechanism of IFN-β suppression has not yet been elucidated. Methods: IFN-β production and downstream autocrine signaling were assessed via quantitative real-time PCR (qRT-PCR) and Western blotting in TNBC cells following exposure to OSM. RNA-sequencing (RNA-seq) was used to assess an IFN-β metagene signature, and to assess the expression of innate immune sensors, which are upstream activators of IFN-β. Cell migration was assessed using an in vitro chemotaxis assay. Additionally, TNBC cells were exposed to TGF-β1, Snail, and Zeb1, and IFN-β production and downstream autocrine signaling were assessed via RNA-seq, qRT-PCR, and Western blotting. Results: Here, we identify the repression of Toll-like Receptor 3 (TLR3), an innate immune sensor, as the key molecular event linking OSM signaling and the repression of IFN-β transcription, production, and autocrine IFN signaling. Moreover, we demonstrate that additional epithelial-mesenchymal transition (EMT)-inducing factors, such as TGF-β1, Snail, and Zeb1, similarly suppress TLR3-mediated IFN-β production and signaling. Conclusions: Our findings provide a novel insight into the regulation of TLR3 and IFN-β production in TNBC cells, which are known indicators of treatment responses to DNA-damaging therapies. Furthermore, strategies to stimulate TLR3 in order to increase IFN-β within the TME may be ineffective in stem-like/mesenchymal cells, as TLR3 is strongly repressed. Rather, we propose that therapies targeting OSM or OSM receptor (OSMR) would reverse the stem-like/mesenchymal program and restore TLR3-mediated IFN-β production within the TME, facilitating improved responses to current therapies.

overall_design: RNA-seq profiling of BT-549 cells transduced with a lentivirus encoding either Oncostatin M (OSM), Transforming Growth Factor Beta 1 (TGF-B1), Snail (SNAI1), Zeb1 (ZEB1), or a an empty lentiviral vector (Vec).

first: Mark

last: Jackson


title: Effect of deletion of UTX expression in NY8.3 progenitor CD8+ T cells

first: Ho Chung

address: 609 Charles E Young Dr E

department: MIMG

institute: University of California, Los Angeles

summary: Type 1 diabetes (T1D) is a chronic autoimmune disease resulting from the destruction of insulin-producing beta cells. This persistence is due to the continual replenishment of short-live effector CD8+ T cells (autoimmune mediators, Tmed) in the pancreatic lymph nodes (pLNs) by a long-lived reservoir of stem-like memory CD8+ T cells (autoimmune progenitors, Tprog). We are investigating an epigenetic regulator UTX playing the role in Tprog to Tmed conversion. The NOD mice with T cell-specific UTX deficiency (UTXTCD mice) were protected from T1D. In addition, the deletion of UTX in CD8+ T cells resulted in the accumulation of Tprog and loss of Tmed populations in pLNs. The function of UTX is to demethylate the histone mark, H3K27 tri-methylation, leading to the open chromatin accessibility for gene expression. ATAC-seq and RNA-seq of antigen specific Tprog cells revealed a role of UTX in closing chromatin at progenitor gene loci while enforcing accessibility at effector gene loci. Taken together, these findings point to the potential of targeting UTX-mediated conversion of Tprog into Tmed for interrupting the T1D autoimmune response.

overall_design: To investigate the gene expression and chromatin accessibility regulated by UTX, we sorted the Ly108+CXCR6- CD8+ T cells harvested from pancreatic lymph node of NOD.NY8.3 (NY8.3) mice and T cell specific deletion UTX deficient NY8.3 mice (UTXTCD.NY8.3). We then perform gene expression profiling using RNA-seq and ATAC-seq. There are 3 samples for each group (NY8.3 and UTXTCD.NY8.3)

first: Shirley

last: Zhang

first: Lisa

last: Kohn

first: Hsing Hui

last: Wang

first: David

last: Sailer

first: Ethan

last: McCarthy

first: Maryam

last: Seyedsadr

first: Zikang

last: Zhou

first: Xihui

last: Yin

first: Nicole

last: Wilkinson

first: Melissa

last: Lechner

first: Willy

last: Hugo

first: Maureen

last: Su


title: CD8+MTs+ Effector T Cells from Enlarged Tumor-Draining Lymph Nodes Drive Enhanced  Tumor Immunogenicity and Improved Prognosis in Colorectal Cancer Patients

city: Harbin

first: Tiantongfei

last: Jiang

state: Heilongjiang

address: 黑龙江省哈尔滨市保健路157号

department: bioinformatics science and technology

institute: harbin medical university

summary: Tumor-draining lymph nodes (TDLNs) play a crucial role in anti-tumor immunity. However, the  heterogeneity of TDLNs significantly impacts their immune function. We employed single-cell  RNA sequencing to dissect the immune landscape of TDLNs of colorectal cancer (CRC), revealing  that enlarged non-metastatic TDLNs (L-TDLNs) are enriched with CD8+ effector T cells (Teff)  exhibiting a distinct metallothionein (MT)-positive signature. These CD8+MTs+ Teff cells,  characterized by heightened cytotoxicity and a stress-adapted phenotype, are critical mediators of  anti-tumor immunity. Our data indicate that these cells migrate from L-TDLNs to tumor sites,  enhancing tumor immunogenicity. Moreover, CRC patients with a high level of CD8+MTs+ Teff in  tumor site showed a significant survival advantage, particularly when treated with adjuvant  chemotherapy. These findings underscore the importance of L-TDLNs in shaping effective antitumor immune responses in CRC, suggesting that the CD8+MTs+ Teff cell population may serve as  a novel prognostic biomarker and therapeutic target. Our study provides a comprehensive  framework for understanding the cellular dynamics within TDLNs and their impact on CRC  progression and treatment response.

overall_design: To elucidate the ecosystem of primary CRC and especially the different TDLNs, we first used  droplet-based scRNA-seq to profile the transcriptomes of 57,427 cells from 8 fresh CRC samples, including 2 CRC, 2 metastatic TDLNs (M-TDLNs), 4 non-metastatic TDLNs (N-TDLNs) tissues.

first: Xu

last: Guan

first: Ran

last: Wei

first: Chongwen

last: Lv


title: COMPARATIVE SINGLE CELL PROFILING OF MUCOSA AND ORGANOIDS IMPLICATES ALTERED EPITHELIAL-MESENCHYMAL INTERACTIONS MEDIATED BY PTGER4 IN PERIANAL FISTULIZING CROHN’S DISEASE

status: Public on Nov 22 2024

city: Atlanta

first: Subra

last: Kugathasan

state: GA

address: 1760 Haygood Dr

department: Pediatrics

institute: Emory University

summary: Background and aims: Perianal fistulizing Crohn’s disease (CD) is severe and often more difficult to treat than luminal CD. Current therapeutics focusing solely on the immune system neither target epithelial and mesenchymal compartments nor consider genetic/epigenetic mechanisms, potentially missing causative aspects of the disease. Thus, the mucosal cells and organoids from a cohort of perianal fistulizing CD patients and controls with diverse genetic backgrounds were experimentally examined. Results: Overall, 140,503 mucosa and 77,044 organoid cells were sequenced. Inflamed perianal CD showed changes across the mucosal compartments (epithelium, immune, stromal), the most dramatic taking place in the epithelium. Epithelial changes occurring in the rectum of perianal CD patients associated with inflammation, gender, and ancestry, and were accompanied by a reduction in differentiated lineages. Organoids from the patient cohort retained both the gender- and ancestral-specific gene expression but did not overwhelmingly reflect their disease status. Organoids lacked bona fide differentiated lineages, but secretory pathways were promoted through PGE2-PTGER4 signaling and HDAC function. Conclusion: Epigenetic modifications are disrupted in the epithelium during inflammation and perianal fistulizing CD that affect the differentiation capacity of those cells, limiting their production/function and thus diminishing the ability of the patients’ mucosal tissue to heal. These epigenetic modifications appear to be modulated by crosstalk between the epithelial and mesenchymal cells, and thus might be leveraged therapeutically.

overall_design: Patient mucosal biopsies and organoids were subjected to single cell RNA sequencing, biochemical, and microscopic analysis. Single-cell transcriptional activity was investigated via principal components, cell type proportions, enriched pathways, and receptor-ligand interactions.

first: Shanta

last: Murthy

first: Murugadas

last: Anbazhagan

first: Sushma

last: Maddipatla

first: Vasantha

last: Kolachala

first: Anne

last: Dodd

first: Jeeya

last: Sharma

first: Amanda

last: Randunne

first: Duke

last: Geem

first: Ranjit

last: Pelia

first: Savannah

last: Washburn

first: Yeonjoo

last: Hwang

first: Tarun

last: Koti

first: Sharmistha

last: Rudra

middle: J

last: Cutler

first: Jason

last: Matthews


title: Suppression of neurons in circumventricular organs enables months-long survival without water in thirteen-lined ground squirrels

city: New Haven

first: Madeleine

last: Junkins

state: Connecticut

address: 333 Cedar Street

department: Cellular & Molecular Physiology; Neuroscience

institute: Yale University

summary: Water deprivation is a life-threatening condition that engages a protective physiological response to couple osmolyte retention with potentiation of thirst. This response, typical for most mammals, safeguards against short-term water deprivation, but fails in the long-term. Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) employ the short-term response during summer, whereas during winter they lack thirst and survive without water for months. Here, we show that long-term thirst suppression occurs despite hormonal and behavioral signs of a dramatic fluid deficit and originates from hypoactivity of neurons in the circumventricular organs, which exhibit marked functional suppression during winter that blunts their sensitivity to thirst cues. Our work reveals a remarkable capacity of the evolutionarily conserved brain regions which control fluid homeostasis in mammals to enable long-term survival without water.

overall_design: Gene expression analysis and differential transcriptomics of the subfornical organ (n = 5 biological replicates) across active (non-hibernating) and interbout arousal (IBA) (hibernating) states in thirteen-lined ground squirrel.

first: Ni

last: Feng

first: Sviatoslav

last: Bagriantsev

first: Elena

middle: O

last: Gracheva


title: FTO degradation targeting enhances anti-tumor immunity

city: Chicago

first: Yanhong

last: Cui

state: IL

address: 5841 S Maryland Ave

institute: University of Chicago

summary: The m6A RNA demethylase Fat mass and obesity-associated protein (FTO) is aberrantly upregulated in numerous cancers and promotes tumor development and therapeutic resistance. Here, using public datasets and screening, we show that FTO is ubiquitinated at lysine 162 by its E3 ligase DTX2, followed by recognition by UFD1, leading to degradation in the proteasomes. Furthermore, we identified vitamin E succinate (VES) as a natural first-in-class degrader for FTO by binding to FTO and DTX2, thus enhancing FTO-DTX2 interaction, leading to increased FTO ubiquitination and degradation and enhanced anti-tumor immunity and response to immunotherapy. Genetic or pharmacological FTO knockdown by VES increased m6A methylation in the LIF gene and thus decreased LIF mRNA decay, and thus sensitized tumor cells to T cell-mediated cytotoxicity. Taken together, our findings elucidated the underlying molecular mechanism for FTO protein degradation and the first natural FTO degrader that reprograms the anti-tumor immunity.

overall_design: RNA Seq of MEL624 cells treated with Vehicle or 25uM Vitamin E succinate for 72 hours.

first: Emma

last: Wilkinson


title: Identification of REEP6 regulated genes and signaling pathways through RNA sequencing

status: Public on Nov 20 2024

city: Shiyan

first: Qin

last: Shanshan

address: Renmin Road 30, Maojian District

institute: Institute of Basic Medical Sciences, School of Basic Medical Sciences, Hubei University of Medicine

summary: This study aimed to explore the underlying molecular mechanism of REEP6 in OSCC progression.  REEP6 plays a role in cellular ferroptosis.

overall_design: The estabilished OSCC cell lines (negative control and REEP6-overexpression) were seeded into 6-well plates and grown overnight. The differentally expressed genes by REEP6 overexpression were screened by RNA sequencing. The transcriptome sequencing studies were performed by deep sequencing, using Illumina NovaSeq 6000.

first: Shanshan

last: Qin

first: Lingyun

last: Xia


title: The PNUTS phosphatase complex controls transcription pause release [cTT-seq]

city: Oxford

first: Emilia

last: Dimitrova

institute: University of Oxford

summary: Gene expression is regulated by controlling distinct steps of the transcriptional cycle, including initiation, pausing, elongation, and termination. Kinases phosphorylate RNA Polymerase II and associated factors to control transitions between these steps and act as central gene regulatory nodes. Similarly, phosphatases that dephosphorylate these components are emerging as important regulators of transcription, though their roles remain less well understood. Here we discover that the mouse PNUTS-PP1 phosphatase complex plays an essential role in controlling transcription pause release in addition to its previously described function in transcription termination. Transcription pause release by the PNUTS complex is essential for almost all RNA Pol II-dependent gene transcription, relies on its PP1 phosphatase subunit, and controls the phosphorylation of factors required for pause release and elongation. Together, these findings reveal an essential new role for a phosphatase complex in transcription pause release and shows that the PNUTS complex is essential for RNA Pol II-dependent transcription.

sample_organism:
Drosophila melanogaster
Mus musculus

platform_organism:
Drosophila melanogaster
Mus musculus

overall_design: Transcription profiling using spike-in calibrated transient transcriptome-sequencing (cTT-seq) of embryonic stem cells in which PNUTS-dTAG can be conditionally depleted upon addition of dTAG13. Rescue with PNUTS WT, W401A or TND-M can be induced with DOX.

first: Robert

last: Klose


title: m6A sites in the coding region trigger translation-dependent mRNA decay (YTHDF2 iCLIP2)

city: Würzburg

first: Julian

last: Konig

address: Am Hubland

institute: Würzburg University

summary: N6-Methyladenosine (m6A) is the predominant internal RNA modification in eukaryotic messenger RNAs (mRNAs) and plays a crucial role in mRNA stability. In this study, we reveal that m6A sites in the coding sequence (CDS) trigger CDS–m6A decay (CMD), a novel mRNA decay pathway that is distinct from previously reported m6A-dependent degradation mechanisms. Importantly, CDS m6A sites act considerably faster and more efficiently than those in the 3' untranslated region, which to date have been considered the main effectors of m6A-mediated RNA decay. Mechanistically, CMD depends on translation whereby m6A deposition in the CDS induces ribosome pausing and transcript destabilization. We found that the target transcripts of CMD are recognized by the m6A reader protein YTHDF2, selectively enriched in processing bodies (P-bodies) and degraded via the decapping factor DCP2. Our findings highlight CMD as a previously unknown pathway for m6A-mediated decay, which is particularly important for controlling the expression of developmental regulators and retrogenes.

overall_design: To learn about m6A-dependent binding of YTHDF2 in the transcriptome, we mapped YTHDF2–RNA binding using individual-nucleotide resolution UV crosslinking and immunoprecipitation (iCLIP2) in HEK293T cells with and without m6A depletion for 12 h. The experiment performed in 4 replicates.

first: Nadine

last: Körtel

first: Hannah

last: Back

last: König

first: Anke

last: Busch

first: You

last: Zhou

first: Kathi

last: Zarnack


title: m6A sites in the coding region trigger translation-dependent mRNA decay (SLAM-seq)

overall_design: SLAMseq experiment was performed for total RNA of HEK293T cells in 3 replicates per condition.

first: Miona

last: Corovic


title: Repurposing colforsin daropate to treat MYC-driven high-grade serous ovarian carcinomas

status: Public on Nov 19 2024

city: Philadelphia

first: Matthew

last: Knarr

state: PA

address: 421 Curie Blvd

department: OBGYN

institute: University of Pennsylvania

summary: High-grade serous ovarian cancer (HGSOC) is one of the deadliest cancers for women, with a low survival rate, no early markers, a high rate of recurrence, and few therapeutic options. Forskolin, an activator of cyclic AMP signaling, has several anticancer activities, including against HGSOC, but has limited use in vivo. Its water-soluble derivative, colforsin daropate, has the same mechanism of action as forskolin and is used to treat acute heart failure. Here, we investigated the potential of colforsin daropate as a treatment for HGSOC. We found that colforsin daropate induced cell cycle arrest and apoptosis in cultured HGSOC cells and spheroids, but not in normal fallopian tube secretory cells and ovarian surface epithelial cells. Colforsin daropate also prevented HGSOC cells from invading ovarian surface cell layers in culture. In vivo, colforsin daropate reduced tumor growth, synergized with cisplatin (a standard chemotherapy in ovarian cancer care), and improved host survival in a subcutaneous xenograft model. These anti-tumor effects of colforsin daropate were mediated in part by its reduction in the abundance and transcriptional activity of the oncoprotein c-MYC, which is often increased in HGSOC. Our findings demonstrate that colforsin daropate may be a promising therapeutic that could be combined with conventional therapies to treat HGSOC.

overall_design: To investigate the effects of colforsin daropate on HGSOC, HEYA8 ovarian cancer cells were treated with either vehicle, 1 uM colforsin daropate, 5 uM colforsin daropate, or 10 uM colforsin daropate for 48 hr. We then performed gene expression profiling analysis using data obtained from RNAseq of N=3 biological replicates for each HEYA8 cell treatment condition.


title: Effect of long-term high temperatures on seed maturation and seed coat integrity in Brassica napus

city: Brno

first: Helene

middle: S.

last: Robert

address: Kamenice 5

country: Czech Republic

institute: CEITEC Masaryk University

summary: Cultivation of canola at temperatures above the optimum growth temperature of 21°C for prolonged periods, especially during the flowering stage, resulted in several adverse effects, including rapid vegetative growth, reduced viability of female gametophytes, increased seed abortion rate, accelerated embryo development, and a reduction in seed oil composition (Young et al., 2004; Mácová et al., 2022; Secchi et al., 2023). One of the distinctive phenotypes observed during the seed development of certain canola cultivars subjected to prolonged heat stress affecting the seed yield is the occurrence of the pre-harvest sprouting phenotype (PHS) (Mácová et al., 2022). Misregulation of seed dormancy by abscisic acid and dormancy-related genes is thought to be the primary cause of PHS in many cereal crops (Benech-Arnold & Rodríguez, 2018; Tai et al., 2021). This phenotype is associated with seed coat rupture (SCR), observed in seeds during the early stages of maturation. In this study, we employed a multi-methodological approach to investigate the occurrence of SCR phenotype in seeds of Brassica napus cv. Topas. The results demonstrate that SCR occurs in seeds around 20 days after pollination (20DAP) when the plants are cultivated in elevated temperatures over an extended period. The unrestricted embryonic growth exerts pressure on the seed coat, as evidenced by a reduction in the thickness of the seed coat cell layers. This results in an early alteration to the cell wall composition, with an increased proportion of demethylesterified pectin, which is likely to stiffen the seed coat, thereby rendering it more susceptible to rupture. The precise mechanism by which accelerated embryo development influences heat stress-mediated seed development in canola plants has yet to be elucidated.

overall_design: To investigate the impact of high temperature on seed coat rupture, we collected seeds of Brassica napus cv. Topas at 14 days after pollination (DAP), 18 DAP, and 20DAP from plants grown in control conditions (TCT) (21oC day / 18oC night, long-day) and high-temperature conditions (THT) (32oC day / 18 oC night, long-day). Plants were moved to THT at the start of bolting, and kept in THT until ripenning. Samples of 20DAP seeds at THT with SCR phenotype were also collected. We performed gene expression profiling analysis using data obtained from RNA-seq for these 3 samples at TCT and 4 samples at THT at 3 time points, in four biological replicates.

first: Unnikannan

last: Prabhullachandran

first: Alejandro

last: Medaglia-Mata


title: m6A sites in the coding region trigger translation-dependent mRNA decay (RNA-seq)

overall_design: In order to study the impact of m6A sites on transcripts, we performed RNA-seq experiments to quantify transcript expression in HEK293T cells upon depletion of m6A using the METTL3 inhibitor STM2457 for 6 and 9 h. The RNA-seq experiment for 6 h and 9 h m6A depletion was performed in 3 and 4 replicates, respectively. Moreover, to investigate the role of YTHDF2 in CDS m6A decay, we performed the RNA-seq experiments to quantify the transcript abundance changes upon YTHDF2 knockdown and combination of YTHDF2 knockdown and 6 h m6A depletion (3 replicates each).


title: The PNUTS phosphatase complex controls transcription pause release [ChIP-Seq]

overall_design: Profiling the genomic distribution of RNA Pol II, PNUTS, and complexes involved in regulation of the early stages of transcription in PNUTS-dTAG mESCs, in which PNUTS can be conditionally depleted with dTAG-13. For some experiments, rescue with wild type PNUTS, W401A  PNUTS or TND-mutant PNUTS were performed.


title: Plasma DNA Methylation-Based Biomarkers for MPNST Detection in Patients With Neurofibromatosis Type 1

city: Houston

first: Keila

middle: E.

last: Torres

state: TX

address: 1515 Holcombe Blvd

department: Surgical Oncology

institute: The University of Texas MD Anderson Cancer Center

summary: Malignant peripheral nerve sheath tumor (MPNST) development is characterized by an altered DNA methylation landscape, which presents a promising area for developing MPNST‐specific biomarkers for screening patients with NF1. Genome‐wide DNA methylation profiling of a cohort of 13 patients with MPNST (29 samples of tumor and adjacent neurofibroma tissues) and of NF1‐MPNST cell lines was performed to identify and validate candidate MPNST‐specific CpG sites (CpGs). A logistic regression prediction model was constructed to select MPNST‐specific CpGs distinct from adjacent neurofibromas and normal tissues. To test if hypermethylation at selected CpGs can also be detected in plasma from patients with MPNST, cfMBD‐seq was applied to profile the cfDNA methylome of blood from patients with MPNST and NF1. Based on stringent feature‐selection criteria and predictive modeling, we identified 73 candidate MPNST‐specific CpGs (67 with unique CpG island locations) that reliably discriminated MPNSTs from neurofibromas. Validation of five candidate biomarkers confirmed successful MPNST detection (sensitivity: > 88%, specificity: > 91%) in tissues. In plasma samples, 63 of 67 selected genomic regions had greater than 1.2‐fold higher methylation in patients with MPNST than those with NF1. Further, we identified 15 CpG islands that consistently separated plasma from patients with confirmed MPNST diagnosis from plasma of individuals with NF1 without a diagnosis of malignant transformation (FDR < 0.1). Our findings confirmed a unique hypermethylation pattern present during malignant transformation. This study highlights the potential to be further investigated further as biomarkers in clinical settings for early MPNST detection in patients with NF1.

overall_design: The methylome analysis was performed on 29 tissue samples from the discovery cohort, the 2 MPNST cell lines (ST88-14 and S462) and 1 NSC line (#8757), each in triplicate. DNA (250 ng) was subjected to methylation profiling using an Infinium HumanMethylation450 BeadChip (450K) assay (Illumina) according to the protocols of the MD Anderson Advanced Technology Genomics Core Facility.

first: Katarzyna

last: Tomczak

first: Manishkumar

last: Patel

first: Angela

last: Bhalla

first: Christine

middle: B

last: Peterson

first: Sharon

middle: M

last: Landers

first: S.

last: Callahan

first: Di

last: Zhang

first: Justin

last: Wong

first: Jace

middle: P

last: Landry

first: Alexander

last: Lazar

first: J.

last: Livingston

first: B.

last: Guadagnolo

first: Heather

last: Lyu

last: Lillemoe

first: Christina

last: Roland

first: Emily

middle: Z

last: Keung

first: Christopher

last: Scally

first: Kelly

middle: K

last: Hunt

first: Ian

last: McCutcheon

first: John

last: Slopis

first: Jian

last: Gu

first: Paul

last: Scheet

first: Liang

last: Wang

first: Kunal

last: Rai


title: Transcriptome Analysis of Fibroblasts in Hypoxia-Induced Vascular Remodeling: Functional Roles of CD26/DPP4

status: Public on Nov 17 2024

city: Chiba

first: Takeshi

last: Kawasaki

address: 1-8-1, Inohana, Chuoku

department: Respirology

institute: Chiba University

summary: In hypoxic pulmonary hypertension (PH), pulmonary vascular remodeling is characterized by the emergence of activated adventitial fibroblasts, leading to medial smooth muscle hyperplasia. Previous studies have suggested that CD26/dipeptidyl peptidase-4 (DPP4) plays a crucial role in the pathobiological processes in lung diseases. However, its role in pulmonary fibroblasts in hy-poxic PH remains unknown. Therefore, we aimed to clarify the mechanistic role of CD26/DPP4 in lung fibroblasts in hypoxic PH. Dpp4 knockout (Dpp4 KO) and wild-type (WT) mice were exposed to hypoxia for 4 weeks. The degree of PH severity and medial wall thickness was augmented in Dpp4 KO mice compared with that in WT mice, suggesting that CD26/DPP4 plays a suppressive role in the development of hypoxic PH. Transcriptome analysis of human lung fibroblasts cultured under hypoxic conditions revealed that TGFB2, TGFB3, and TGFA were all upregulated as differentially expressed genes after DPP4 knockdown with small interfering RNA treatment. These results suggest that CD26/DPP4 plays a suppressive role in TGFβ signal-regulated fibroblast ac-tivation under hypoxic conditions. Therefore, CD26/DPP4 may be a potential therapeutic target in patients with PH associated with chronic hypoxia.

overall_design: To explore the potential effects of CD26/DPP4 on HLFs under hypoxic conditions, we performed RNA sequencing of HLFs treated with negative control siRNA (Control) or DPP4-siRNA (DPP4 KD) cultured under normoxic or hypoxic conditions.

first: Yuri

last: Suzuki

first: Koichiro

last: Tatsumi

first: Tadasu

last: Okaya

first: Shun

last: Sato

first: Ayako

last: Shimada

first: Tomoko

last: Misawa

first: Ryo

last: Hatano

first: Chikao

last: Morimoto

first: Yoshitoshi

last: Kasuya

first: Yoshinori

last: Hasegawa

first: Osamu

last: Ohara

first: Takuji


title: Tumor-associated neutrophils attenuate the immuno-sensitivity of hepatocellular carcinoma and curtail immunotherapy response

status: Public on Nov 18 2024

city: Hong Kong

first: Nickolas

last: Teo

address: 1/F, Laboratory Block, 21 Sassoon Road

department: SBMS

country: Hong Kong

institute: HKU

summary: This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series


title: Effect of iron-overload on gene expression in atherosclerosis

first: Xiang

last: Peng

address: Baojian Street

institute: The Second Affiliated Hospital of Harbin Medical University

summary: The aim of this study was to identify novel key genes and to investigate pathways involved in effect of iron-overload on atherosclerosis

overall_design: Apoe-/- mice (6-8 weeks old) under a 24-week regimen of chow diet (CD) and high fat diet (HFD) with or without intraperitoneal injection of ammonium iron(III) citrate (HFD+IO). The atherosclerotic aorta was harvested and performed RNA-seq analysis.

first: Jinwei

last: Tian


title: Effects of physical activity reduction on the gastrocnemius transcriptome

city: Downers Grove

first: Erin

last: Stephenson

address: 555 31st street

institute: Midwestern University

summary: Insufficient physical activity is associated with increased relative risk of cardiometabolic disease and is an independent risk factor for mortality. Experimentally reducing physical activity rapidly induces insulin resistance, impairs glucose handling, and drives metabolic inflexibility. These adaptations manifest during the early stages of physical inactivity, even when energy balance is maintained, suggesting that inactivity-mediated metabolic reprogramming is an early event that precedes changes in body composition. To identify mechanisms that promote metabolic adaptations associated with physical inactivity, we developed a mouse model of physical activity reduction that permits the study of inactivity in animals prior to the onset of overt changes in body composition. Adult mice were randomized into three groups: an inactive control group (standard housing), an active control group (treadmill running for 6-weeks), and an activity reduction group (treadmill running for 4-weeks, followed by 2-weeks of inactivity). Transcriptional profiling of gastrocnemius muscle was performed.

overall_design: 10 week old female C57BL6/NJ mice either remained sedentary (standard housing and enrichment), treadmill trained 5 d/week for 40 min/session at 70% of maximal running speed for 6 weeks, or treadmill trained for 4 weeks followed by 2 weeks of inactivity. Tissues were collected in the 5-6 h fasted state after 48-72 h had passed since the final exercise session (which was a maximal running test that all mice regardless of group assignment undertook).


title: Nuclear EGFR in breast cancer suppresses NK cell recruitment and cytotoxicity

status: Public on Nov 15 2024

city: Tucson

first: Angelica

last: Escoto

state: AZ

address: 1007 E Lowell St

department: Molecular & Cellular Biology

institute: University of Arizona

summary: Natural Killer (NK) cells can target and destroy cancer cells, yet tumor microenvironments typically suppress NK cell recruitment and cytotoxicity. Recent work has demonstrated a novel role for nuclear EGFR (nEGFR) in regulating transcriptional events unique from the kinase domain. Using a novel peptide therapeutic (cSNX1.3) that inhibits retrograde trafficking of EGFR and an EGFR nuclear localization mutant, we discovered that nEGFR suppresses NK cell recruitment and cytotoxicity. RNA-seq analysis of breast cancer cells treated with cSNX1.3 or modified to lack a nuclear localization sequence (EGFRΔNLS) revealed the EGF-dependent induction of NK activating antigens, while kinase inhibition by erlotinib did not impact these genes. Together, the data demonstrate a unique immunomodulatory role for nEGFR.

overall_design: To investigate the function nEGFR vs. EGFR kinase activity has on the regulation of NK cell-related genes, we used a nEGFR inhibitor, cSNX1.3, or breast cancer cells modified to lack a nuclear localization sequence (EGFR ΔNLS), and an EGFR kinase inhibitor, erlotinib. We then looked at genes differentially expressed under all conditions using data from RNA-Seq analysis.


title: UVB exposure triggers autoimmune cutaneous inflammation in Foxp3dExon2-expressing mice.

status: Public on Nov 14 2024

city: Seattle,

first: Stephanie

last: Osmond

state: WA

address: 1201 9th Ave

institute: Benaroya Research Institute

summary: Ultraviolet B (UVB) light is a common environmental trigger that can induce flares in several autoimmune diseases. Here, we modeled photosensitivity in mice which express an autoimmune-driving isoform of Foxp3 without the second coding exon of the gene, called FoxP3ΔE2 mice. In the steady-state, FoxP3ΔE2mice generate keratinocyte-specific IgE autoantibodies and more autoreactive T follicular helper (TFH) cells that target keratinocyte-derived autoantigens that are released upon exposure to damaging doses of UVB. After UVB light challenge in vivo, FoxP3ΔE2mice generated more IgE antibodies, increased germinal center formation, had higher percentages of IL-4+TFHs, developed worsened skin pathology and had higher concentrations of IgE in UVB-damaged skin. We also observed a significant increase in IgE on basophils and accumulation of basophil extracellular traps in UVB-challenged skin of FoxP3ΔE2mice. Collectively, FoxP3ΔE2mice fail to maintain self-tolerance in GCs, causing IgE autoantibody production and driving exaggerated photosensitivity.

overall_design: Foxp3-WT and Foxp3-DE2 mice were treated with 6 doses of UVB light (100mJ/cm2) on a shaved patch of skin (3cm x 2cm) on the back flank of each mouse. Total RNA was extracted from skin from the UVB-treated site (+UVB) and a non-treated control site (-UVB) and processed for bulk RNA sequencing.

first: Phillip

last: Domeier

first: Caroline

last: Stefani

first: Shuting

last: Chen

first: Aqsa

last: Mohammed

first: Jessica

last: Snyder

first: Baohua

last: Zhou

first: Adam

last: Lacy-Hulbert

first: Paul

last: Utz

middle: C

last: Eisenbarth

first: Steven

middle: F

last: Ziegler


title: Polycomb protein RYBP facilitates super-enhancer activity

status: Public on Nov 13 2024

city: Guangzhou

first: Chao

last: Wei

address: No.74 Zhongshan Rd.2

institute: Sun Yat-Sen University

summary: Background Polycomb proteins are conventionally known as global repressors in cell fate determination. However, recent observations have shown their involvement in transcriptional activation, the mechanisms of which need to be further revealed. Methods Herein, multiple data from ChIP-seq, RNA-seq and HiChIP before or after RYBP depletion in embryonic stem cell (ESC), epidermal progenitor (EPC) and mesodermal cell (MEC) were analyzed. Results We found that Polycomb protein RYBP occupies at super-enhancer (SE) in ESCs, where core Polycomb group (PcG) components such as RING1B and EZH2 are minimally enriched. Depletion of RYBP results in impaired deposition of H3K27ac, decreased expression of SE-associated genes, and reducing the transcription of enhancer RNA at SE regions (seRNA). Regarding the mechanism of seRNA transcription, the Trithorax group (TrxG) component WDR5 co-localizes with RYBP at SEs, and is required for seRNA expression. RYBP depletion reduces WDR5 deposition at SE regions. In addition, TrxG-associated H3K4me3 tends to be enriched at the SEs with high levels of seRNA transcription, and RYBP deficiency impairs the deposition of H3K4me3 at SEs. Structurally, RYBP is involved in both intra- and inter-SE interactions. Finally, RYBP generally localizes at SEs in EPCs and MECs, dysfunction of RYBP is associated with various cancers and developmental diseases. Conclusion RYBP cooperates with TrxG component to regulate SE activity. Dysfunction of RYBP relates to various diseases. The findings provide new insights into the transcriptionally active function of Polycomb protein in cell fate determination.

overall_design: RYBP ChIP-seq in rat cardiomyocytes

first: Yu

last: Hong

first: Ranran

last: Dai

first: Xinlan

last: Li


title: Mina53 regulates the expression of downstream genes in NSPC cells by its arginine demethylase activity on H4R3me2a

city: Hangzhou

first: Lixiao

address: Yuhangtang road

institute: Zhejiang University

summary:
In order to investigate the role of Mina53 in the NSPC proliferation and differentiation,
we performed RNA-seq using Mina53-KO NSPCs and wild-type NSPCs;
we performed CUT-TAG using anti-H4R3me2a antibody in Mina53-KO NSPCs and wild-type NSPCs.

overall_design:
NSPCs were extracted from relative mice and then purified. Then these cells were suspended using trizole.
NSPCs were extracted from relative mice and then purified. Then these cells were performed CUT-TAG assay using NovoNGS® CUT&Tag 4.0 High-Sensitivity Kit (for Illumina®).

Please note that the records have been updated with the CUT-TAG samples on Dec 13, 2024.


title: Pancreatic β-cell interleukin-22 receptor subunit alpha 1 deficiency impairs β-cell function in type 2 diabetes via cytochrome b5 reductase 3 [shRNA]

status: Public on Nov 12 2024

city: Shanghai

first: Hong

last: Zhang

address: 600 Yishan Road

department: Shanghai Diabetes Institute

institute: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

summary: Impaired β-cell function is a hallmark of type 2 diabetes (T2D), whereas, the underlying cellular signaling machineries that regulate β-cell function remain unknown. Here, we identify that the interleukin-22 receptor subunit alpha 1 (IL22RA1), known as a co-receptor for IL-22, is downregulated in human and mouse T2D β-cells. Mice with β-cell Il22ra1 knockout (Il22ra1βKO) exhibit defective insulin secretion and impaired glucose tolerance after a high-fat diet (HFD) or HFD/low-dose streptozotocin (STZ). Mechanistically, β-cell IL22RA1 deficiency inhibits cytochrome b5 reductase 3 (CYB5R3) expression via the IL22RA1/STAT3/c-JUN axis, thereby impairing mitochondrial function and reducing β-cell identity. Overexpression of CYB5R3 reinstates mitochondrial function, β-cell identity and insulin secretion in Il22ra1βKO mice. Moreover, pharmacological activation of CYB5R3 with tetrahydroindenoindole restores insulin secretion in Il22ra1βKO mice, IL22RA1 knockdown human islets and Min6 cells. In conclusion, these findings suggest an important role of IL22RA1 in preserving β-cell function in T2D, which offers a potential therapeutic target for treating diabetes.

overall_design: To investigate the influence of changes in transcriptional patterns that modulate β-cell function via IL22RA1 signaling, we performed RNA-sequencing (RNA-seq) on Min6 cells infected with adenovirus sh-ctrl versus those infected with sh-Il22ra1 after PA treatment

first: Fan

last: Yu

first: Cheng

last: Hu


title: Biodegradable Janus sonozyme with continuous reactive oxygen species regulation for treating infected critical-sized bone defects

city: wuhan

first: zixuan

last: Ou

state: hubei

address: 1277 Liberation Avenue, Kong Hon

department: Tongji Medical College

institute: Huazhong University of Science and Technology

summary: Critical-sized bone defects are usually accompanied by bacterial infection leading to inflammation and bone nonunion. However, existing biodegradable materials lack long-term therapeutical effect because of their gradual degradation. Here, a degradable material with all time ROS modulation is proposed, defined as a sonozyme due to its functions as a sonosensitizer and a nanoenzyme. Before degradation, the sonozyme can exert an effective sonodynamic antimicrobial effect through the dual active sites of MnN4 and Cu2O8. Furthermore, it can promote anti-inflammation by superoxide dismutase and catalase activities. Following degradation, quercetin-metal chelation exhibits a sustaining antioxidant effect through ligand-metal charge transfer, while the released ions and quercetin also have great self-antimicrobial, osteogenic, and angiogenic effects. A rat model of infected cranial defects demonstrates the sonozyme can rapidly eliminate bacteria and promote bone regeneration. This work presents a promising approach to engineer biodegradable materials with long-time effects for infectious bone defects.

overall_design: In order to elucidate the mechanism by which MON(CuMn)-Q promotes osteogenesis, RNA sequencing was employed on hBMSCs. Two groups were established, comprising the control and MON(CuMn)-Q groups. The control group was maintained in a continuous culture of medium lacking any material for a period of 21 days, while the MON(CuMn)-Q group was subjected to a 21-day culture in a medium containing 150 µg/mL MON(CuMn)-Q. Following this, both groups underwent RNA sequencing.

first: Zixuan

first: Junyu

first: Jie

last: Lei

first: Xiaobo

last: Feng


title: Pancreatic β-cell interleukin-22 receptor subunit alpha 1 deficiency impairs β-cell function in type 2 diabetes via cytochrome b5 reductase 3 [BKO]

overall_design: To investigate the influence of changes in transcriptional patterns that modulate β-cell function via IL22RA1 signaling, we performed RNA-sequencing (RNA-seq) on islets isolated from 6-week HFD-fed Ins2Cre mice and Il22ra1βKO mice