title: PRICKLE4 Underlies IDH mutant Tumors Resistance against PARP Inhibition

city: shanghai

first: Giero

state: Shanghai

address: dong an road

institute: Fudan university

summary: Mutations in isocitrate dehydrogenase (IDH) genes render affected gliomas sensitive to PARP inhibition due to epigenetic reprogramming of the DNA damage repair circuits. However, PARPi treated tumor eventually relapse. We report in this study that anti-angiogenetic agent lenvatinib efficiently cooperate with PARPi and the combination therapy induces marked tumor regression and significant extension of survival time. Genomic study with PARPi and lenvatinib treated tumor samples uncovered that PARPi evokes global transcriptome changes that are overall pro-inflammatory, thus inducing tumor angiogenesis. We identified that prickle planar cell polarity protein 4 (Prickle4) as the specific mediator for PARPi induced neovascularization. Suppression of Prickle4 efficiently overcomes PARPi resistance in these tumors. Overall, multimodality therapy combining PARPi and anti-angiogenetic agents represents a feasible treatment that is of excellent potential for clinical applications.

overall_design: Veliparib and lenvatinib together displayed prominent tumor regressive activity that neither of the two administrated alone achieved. We reasoned that this activity may be linked to molecular changes post one drug treatment that render tumor cells sensitive to another, rather than a simple combinatory effect of drugs. It is also possible that the resistent mechanisms that one drug treatment stimulated is overcome by its corresponding blockade agent. And information of these changes can only be broadly captured by genomic studies to elaborate these mechanisms. To determine this, we subjected fresh tumor samples 9 days post treatment regimens to transcriptional profiling with bulk RNA sequencing.


title: Burdock miR8175 improves insulin sensitivity in DIO mice by targeting PTP1B and PTPRF

status: Public on May 01 2024

city: Nanjing

first: Huichen

last: Song

state: Jiangsu

address: Qixia District, Xianlin Road No.163

country: China

institute: Nanjing university

type: Non-coding RNA profiling by high throughput sequencing

type: Expression profiling by high throughput sequencing

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

sample_organism:
Arctium lappa
Mus musculus

platform_organism:
Arctium lappa
Mus musculus

overall_design: Refer to individual Series


title: Stem Cell-derived Microglia Exhibit HAND Gene Expression Signature Early Upon Infection with HIV-1 [iPSCMG]

city: Cincinnati

first: Jason

last: Hammonds

state: Ohio

address: 3333 Burnet Ave

department: Infectious Diseases

country: USA

institute: Cincinnati Children's Hospital Medical Center

summary: HIV-associated neurocognitive disorders (HAND) persist as a notable cause of illness among individuals with HIV. Despite significant progress in antiretroviral therapy (ART), HAND continues to be a major concern, impacting approximately one-third of those infected with HIV. Recent research underscores the pivotal role of microglia, the primary immune cells in the central nervous system (CNS), in the development and progression of HAND. The infection and activation of microglia by HIV leads to the release of pro-inflammatory markers, cytokines, chemokines, secondary messengers, and reactive oxygen species (ROS). These factors collectively initiate signalling pathways that contribute to neuroinflammation, a central process in the development of HAND. In order to validate stem cell-derived microglia (iMGL) as a viable model system for HAND investigation, we infected iMGLs and human monocyte-derived macrophages (MDMs) with the primary HIV-1 isolate Ba-L at an MOI of 0.25. Total RNA was extracted from cell populations on days 1, 2, 4, 6, and 8 following infection. Subsequently, we conducted bulk RNA sequencing to examine the longitudinal transcriptomic alterations induced by the virus over this time frame

overall_design: To demonstrate the effect of an HIV-1 infection time course on the gene expression profile of iPSC-derived microglia-like cells (iMGLs).

first: Roy

last: Moscona

first: Kathleen

last: Candor

first: Thomas

last: Hagan

first: Paul

last: Spearman


title: Transcriptomics on RCaP celline

city: Cold Spring Harbor

first: Lloyd

last: Trotman

state: New York

address: 1 Bungtown Road

institute: Cold Spring Harbor Laboratory

summary: Transcriptomics on RCaP celline. RCaP is a primary line derived from the RapidCaP mouse model

overall_design: RCaP cell line was grown in complete media; two biological replicates. RNA was extracted and transcriptome profiles generated.

first: Grinu

last: Mathew

first: Sarah

middle: D

last: Diermeier

first: Aashna

last: Jhaveri

middle: C


title: Stem Cell-derived Microglia Exhibit HAND Gene Expression Signature Early Upon Infection with HIV-1 [MDM]


title: IRF4 requires ARID1A to establish plasma cell identity in multiple myeloma (ATAC-Seq  human 16)

city: Bethesda

first: David

last: Huang

state: Maryland

address: 9000 Rockville Pike

institute: National Cancer Institute

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Multiple myeloma (MM) is an incurable malignancy of plasma cells that exploits transcriptional networks underpinning normal plasma cell biology to drive malignant growth and survival. The transcription factor IRF4 serves as the principal architect of plasma cell identity, and MM cells are addicted to IRF4 expression for their survival. To discover unique molecular vulnerabilities in MM, we employ a multi-omics approach integrating functional genomics screening, spatial-proteomics, and global chromatin mapping. We find that ARID1A, a member of the SWI/SNF chromatin remodeling complex, is both required for IRF4 expression and functionally associated with IRF4 protein on chromatin. Conditional deletion of Arid1a in activated murine B cells thwarts subsequent plasma cell differentiation by disrupting IRF4-dependent transcriptional networks, thus defining ARID1A as a novel plasma cell vulnerability. Targeting ARID1A-dependent SWI/SNF activity via SMARCA2/4 inhibition induces a rapid loss of IRF4-target gene expression and quenches global oncogenic amplification of gene expression driven by MYC, resulting in profound toxicity to MM cells. Notably, SWI/SNF-dependent genes are upregulated in MM patients with aggressive disease, and SMARCA2/4 inhibitors retain their activity in immunomodulatory drug (IMiD)-resistant MM cells. To fully harness the potential of these drugs, we use combinatorial drug screens to uncover profound synergistic toxicity between SMARCA2/4 and MEK inhibitors. Thus, targeting SWI/SNF activity potently represses an IRF4-MYC feed forward loop and provides a feasible path forward to effectively treat this incurable disease.

overall_design: ATAC sequencing to determine chormatin accessibility in NCH929 and SKMM1 multiple myeloma cells treated with control (DMSO), 50 nM FHD286, 50 nM trametinib, or combination (50 nM FHD286 PLUS 50 M trametinib) for 4 hours.

first: Arnold

last: Bolomsky

first: Ryan

middle: M

last: Young


title: Burdock miR8175 improves insulin sensitivity in DIO mice by targeting PTP1B and PTPRF [II]

summary: The incidence of type 2 diabetes (T2DM) induced by obesity is rapidly increasing. Although there are many drugs developed for type 2 diabetes, but the anti-diabetic effect of homology of medicine and food is also very popular with the majority of people. Burdock is one such food, but the molecular mechanism of anti-diabetic effect is unclear, limiting its further promotion. In recent years, studies have shown that plant mirnas can regulate host gene expression through dietary absorption, so plant miRNAs have become one of the main active ingredients in traditional Chinese medicine. Here, we report that miR8175, a plant miRNA from burdock root, has effective antidiabetic activity. miR8175 is highly enriched in burdock decoction. After administration of burdock decoction or synthetic miR8175 by gavage, significantly elevated levels of miR8175 in mouse serum and liver can be observed. Furthermore, both burdock decoction and miR8175 can significantly improve the impaired glucose metabolism of diabetic mice induced by a high-fat diet (HFD). Our results demonstrate that burdock decoction and miR8175 enhance the insulin sensitivity of the hepatic insulin signaling pathway by targeting PTPRF and PTP1B, which may be the reason for the improvement in metabolism.

overall_design: Burdock roots (60 g) were soaked in 700 ml of water for 30 min and were then boiled for 30 min, resulting in ~80 ml of decoction. RNAs from burdock decoction were isolated following the method described above. Illumina sequencing was performed by BGI (Shenzhen, China).


title: Single-nucleus transcriptomic sequencing of aging hypothalamus treated with 17a-estradiol

city: Nantong

first: Yinchuan

last: Li

address: 16 wenfeng road, Chongchuan

department: Medical School

institute: Nantong University

summary: To dissect the role of 17a-estradiol in lifespan extending and its potential side effects for long-term administration, the pooled hypothalami from aging male Norway brown rats treated with 17a-estradiol for 6 months (O.T), aged male control (O), and young male control (Y) were subjected to single-nucleus transcriptomic sequencing (snRNA-seq).

overall_design: 24-month-old-male Norway brown rats were  fed freely with diet mixed with 17a-estradiol at a dose of 14.4 milligrams per kilogram diet (14.4 ppm) starting at 24 months of age for six months (O.T). 30-month-old-male rats and 4-month-old-male rats were used as aging control (O) and young sample control (Y) respectively. All rats had ad libitum access to food and water. The intact hypothalami in each group were pooled for nucleus isolation and snRNA-seq.

first: Shaoyang

last: Ji


title: Burdock miR8175 improves insulin sensitivity in DIO mice by targeting PTP1B and PTPRF [I]

overall_design: To study the target genes of miR8175 in hepatocytes, the biotin-modified miR8175 mimics were transfected into Hepa1-6 cells, and total RNA was collected 24 hours after transfection. The RNA bound to miR8175 was enriched using streptavidin-coated magnetic beads and analyzed by deep sequencing.


title: Stem Cell-derived Microglia Exhibit HAND Gene Expression Signature Early Upon Infection with HIV-1


title: Gene expression profile of Duocarmycin SA-treated human AML cell lines in vitro

city: Memphis

first: Hongjian

last: Jin

state: TN

address: 262 Danny Thomas Place

department: Center for Applied Bioinformatics

institute: St Jude Children's Research Hospital

summary: Acute myeloid leukemia (AML) is a hematological malignancy that is characterized by the expansion of immature myeloid precursors and poor patient survival outcomes. As such there is a need for the evaluation of potential therapeutic candidates that can be used in combination with current treatment regimens to improve patient outcomes. In this study, we investigated the efficacy of DSA on AML cells in vitro and performed gene expression profile analysis of DSA-treated AML cells to identify genes that are regulated by DSA. Here we report DSA-induced differentially expressed genes and cellular pathways that are associated with the functional changes that are observed in DSA-treated AML cells. Our data provides, for the first time, DSA's unique gene signature and provides a mechanistic rationale for DSA-induced functional effects in AML cells.

overall_design: To determine the gene expression profile of DSA-treated human AML cells, human AML cell lines (Molm 14 and HL-60) were cultured with two different concentrations of DSA for 36 hours. At 36 hours, cells were harvested and RNA was isolated from the cells using Qiagen's RNeasy mini kit. RNA concentration and quality was determined using the nanodrop. Gene sequencing was performed by the Hartwell Center for Biotechnology (St. Jude Children's Research Hospital) and gene expression profiling analysis by the Center for Applied Bioinformatics (St. Jude Children's Research Hospital) and Loma Linda University.

first: Olivia

middle: L

last: Francis-Boyle

first: Jun

last: Yang

first: Jie

last: Fang

first: William

middle: A

last: Chen

first: Kristopher

middle: E

last: Boyle


title: Expression data from human colorectal cancer tissues and the corresponding non-cancerous tissues

city: GUANGZHOU

first: PENG

last: SHEN

address: GUANGZHOUDADAOBEI 1838

institute: NANFANG HOSPITAL

summary: To identify ythe the functional roles and the pathophysiological contributions of coding genes and noncoding RNAs in human colorectal carcinogenesis, we analysed the differenial expression of genes and noncoding RNAs in colorectal cancer tissues and the corresponding non-cancerous tissues.


title: To survey ncRNAs that associate with Lsd1 or Bre1 complexes through RIP experiments

city: Taiepi

first: Ming-Chia

last: Lee

address: Library, Info & Research Bldg, Rm 904 #155, Sec. 2, Li-Nong St

department: Department of Life Sciences and Institute of Genome Sciences

country: Taiwan

institute: National Yang Ming Chiao Tung University

summary: These paired RIP experiments were designed to determine specific ncRNAs that associated with either Lsd1 (Lysine specific demethylase 1) complex or Bre1.

overall_design: The RIP experiments were done using fly ovarian lysate collected from young females (<12 hr post eclosion). Specifically, Lsd1-RIP and Bre1-RIP were paired with a IgG-RIP ereaction for normalizing the abundance of individual transcripts.


title: Asparagine endopeptidase deficiency mitigates radiation-induced brain injury by suppressing microglia-mediated neuronal senescence

city: Shanghai

first: Ouwen

last: Qiu

address: 160 Pujian Road

department: Brain Injury Center, Department of Neurosurgery

institute: Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine

summary: Mounting evidence supports the role of neuroinflammation in radiation-induced brain injury (RIBI), a chronic disease characterized by delayed and progressive neurological impairment. Asparagine endopeptidase (AEP), also known as legumain (LGMN), participates in multiple malignancies and neurodegenerative diseases and may potentially be involved in RIBI. Here, we found AEP expression was substantially elevated in the cortex and hippocampus of WT (Lgmn+/+) mice following whole-brain irradiation. Lgmn knockout (Lgmn-/-) alleviated neurological impairment caused by whole-brain irradiation by suppressing neuronal senescence. Bulk RNA and metabolomic sequencing revealed AEP’s involvement in the antigen processing and presentation pathway and neuroinflammation. This was further confirmed by co-culturing Lgmn+/+ primary neurons with the conditioned media derived from irradiated Lgmn+/+ or Lgmn-/- primary microglia. Furthermore, esomeprazole inhibited the enzymatic activity of AEP and RIBI. These findings identified AEP as a critical factor of neuroinflammation in RIBI, highlighting the prospect of targeting AEP as a therapeutic approach.

overall_design: To investigate the role of AEP in regulation of radiation-induced brain injury, three wildtype male Balb/c mice and three Lgmn-knockout male Balb/c mice were irradiated to the whole brain with a dose of 10 Gy X-ray. The cortices were extracted and applied with bulk RNA sequencing.

first: Jianyi

last: Zhao

first: Zhonggang

last: Shi

first: Huan

first: Siyuan

last: Wang

first: Keman

last: Liao

first: Minchao

last: Tang

first: Jieqiong

last: Xie

first: Xi

first: Wenrui

last: Zhang

first: Li

last: Zhou

first: Zhiyi

first: Lei

last: Xu

first: Renhua

first: Yifeng

last: Miao

first: Yongming

first: Yingying

last: Lin


title: Expression data from human colorectal cancer tissues and the corresponding non-cancerous tissues [MeRIP-seq]

first: PENG

summary: To identify the the functional roles and the pathophysiological contributions of the mRNA m6A modification in human colorectal carcinogenesis, we analysed the profile the landscape of the mRNA m6A modification in colorectal cancer tissues and the corresponding non-cancerous tissues.

overall_design: We compare the difference in RNA m6A methylation between CRC tissues and adjacent normal control (NC) tissues using MeRIP-seq.

first: Jian

first: Peng

last: Shen


title: Diurnal control of iron responsive element containing mRNAs through iron regulatory proteins IRP1 and IRP2 is mediated by feeding rhythms

city: Lausanne

first: Hima

middle: Priyanka

last: Nadimpalli

address: Génopode Building, Room 500

country: Switzerland

institute: UNIL - CIG

summary:
Background: Cellular iron homeostasis is regulated by iron regulatory proteins (IRP1 and IRP2) that sense iron levels (and other metabolic cues) and modulate mRNA translation or stability via interaction with iron regulatory elements (IREs). IRP2 is viewed as the primary regulator in liver, yet our previous datasets showing diurnal rhythms for certain IRE-containing mRNAs suggest a nuanced temporal control mechanism. The purpose of this study is to gain insights into the daily regulatory dynamics across IRE-bearing mRNAs, specific IRP involvement, and underlying systemic and cellular rhythmicity cues in mouse liver.

Results: We uncover high-amplitude diurnal oscillations in the regulation of key IRE containing transcripts in liver, compatible with maximal IRP activity at the onset of the dark phase. Although IRP2 protein levels also exhibit some diurnal variations and peak at the light-dark transition, ribosome profiling in IRP2-deficient mice reveals that maximal repression of target mRNAs at this time-point still occurs. We further find that diurnal regulation of IRE-containing mRNAs can continue in the absence of a functional circadian clock as long as feeding is rhythmic.

Conclusions: Our findings suggest temporally controlled redundancy in IRP activities, with IRP2 mediating regulation of IRE-containing transcripts in the light phase and redundancy, conceivably with IRP1, at dark onset. Moreover, we highlight the significance of feeding-associated signals in driving rhythmicity. Our work highlights the dynamic nature and regulatory complexity in a metabolic pathway that had previously been considered well-understood.

overall_design: Twenty four biological samples were used (2 genetic lines x 2 genotypes x 2 time points x 3 replicates). Briefly mice were entraiend for minimum 8 days to light:dark 12:12 (hours) under ad libitum conditions and were euthanized at Zeitgeber times ZT 5 (5 hours after “lights on”) and ZT12 (“lights off”). Three replicates per time point.


title: Spatial transcriptomic profiles of prostate tissue obtained from a patient diagnosed with benign prostatic hyperplasia (BPH).

first: Yanting

address: Miaopu road 219

department: Department of Urology and andrology

institute: Gongli Hospital, the Second Military Medical University

summary: ST profiles reveals the alterations in epithelial cells in Benign Prostatic Hyperplasia.

overall_design: ST was conducted using the Visium platform (10x Genomics). Cryosection from an OCT-embedded BPH tissue sample was placed on Visium spatial slide. The mRNA molecules bound by printed capture oligos, which contained spatial barcodes on the slide, were converted into cDNA. Subsequently, the cDNA was transferred from the slide for library preparation. Spatial libraries were constructed using the Visium Spatial Library Construction Kit (10x Genomics, PN-1000184), following the manufacturer's instructions. Finally, sequencing was performed using HiSeq X10 (Illumina) with 150 bp paired-end reads.


title: Whole-Exome Sequencing Identifies Eight Genes Associated with Recurrent Patellar Dislocation

city: Beijing

first: Zijie

state: Beijing

address: Haidian District, Huayuan Road 49

department: Sports Medicine Department

institute: Peking University Third Hospital

summary: The inheritance of recurrent patellar dislocation (RPD) is konwn, but the susceptible gene remian unidentified. Here, we performed the first whole exome sequencing (WES) cohort study to identify the susceptible genes. The results showed eight genes were associated with this disease. Notably, the CPD gene showed the highest relevance based on its gene function and tissue expression. Single-cell sequencing results indicate that the CPD gene is involved in the pathophysiological process of RPD through granulocytes. Implicated pathways include NF-kappa B, MAPK, and Wnt/β-catenin signaling, potentially influencing CPD's role in RPD pathogenesis. This study identified the susceptible gene and investigate the potential pathogenesis of RPD, which provided a new prospect for the understanding of RPD. Besides, it would offer the theoretical basis for disease prevention and genetic counseling.

overall_design: Bone marrow samples were aspirated from the distal femur of three RPD patients recruited at Peking University Third Hospital. The bone marrow scRNA-seq data of three non-RPD controls were obtained from the periouse published study48. The bone marrow samples were collected into heparin tubes and density gradient centrifugation was used to isolate bone marrow cells. The single-cell RNA libraries were prepared using Chromium Single Cell 5’ Library and Gel Bead Kit. The sequence reads were mapped to the GRCH38 human reference genome using Cell Ranger 6.0.1 (10x Genomics).


title: Erythromycin mediates co-flocculation between cyanobacterium Synechocystis sp. PCC 6803 and filamentous fungi in liquid cultivation without organic compounds.

city: Bangkok

first: Jidapa

last: Leksingto

country: Thailand

institute: Chulalongkorn

summary: Transcriptomic analysis of suspended and flocculated (with the fungi) Synechocystis cells suggested that the EM-mediated co-flocculation was a result of down-regulation of the minor pilin genes and up-regulation of several genes including the chaperone gene for pilin regulation, the S-layer protein genes, the exopolysaccharide-polymerization gene, and the genes for signaling proteins involved in cell attachment and abiotic-stress responses. The EM treatment may be applied in the co-culture between other cyanobacteria and fungi to mediate cell bio-flocculation.

overall_design: Transcriptomic analysis bewteen suspended and flocculated (with the fungi) Synechocystis cells

first: Tanakarn

last: Monshupanee


title: Pharmaceutical inhibition of RAS overcomes cytokine mediated resistance to FLT3 inhibition in FLT3-ITD+ AML [RNA-seq]

city: Birmingham

first: Peter

last: Keane

address: Vincent Drive

department: Institute for Cancer and Genomic Sciences

country: United Kingdom

institute: University of Birmingham

summary: AML is characterised by a variety of co-occurring driver mutations in genes associated with cell signallingand growth regulationsuch as the FLT3-ITD. Inhibitors targeting FLT3 (FLT3i) are beingused to treat FLT3-ITD+ patients but most relapse.By profiling the gene regulatory networks of samples from patients before and after FLT3i treatment weobservedan increase in AP-1 mediated and a loss of RUNX1 mediated connections in treatment resistant cells. Treatmentinducesupregulation of signalling pathway genesindicatingthat cytokines mediate resistance to FLT3i, with IL-3 playing a major role. IL3 rescues survival by counteracting FLT3i mediated globalRUNX1 degradation and adown-regulationof bindingof RUNX1 in chromatin.To identify inhibitors which bypass the RUNX1 barrier we inhibitedMAPK signalling with a novel pan-RAS inhibitor which overcomes cytokine mediated resistance.Our data show (I) that cytokinesinstructAML maintenance via the stabilisation of transcriptional regulators and (ii)pan-RAS drugs bypass thisbarrier, suggesting a novel approach to treatment of AML.

overall_design: RNA-Seq of FLT3-ITD primary AML samples, and FLT3-ITD+ cell lines (MOLM14, MV411) before and after treatment with FLT3 inhibitors, RAS inhibitors and IL3 with replicates

first: Daniel

last: Coleman

last: Cockerill

first: Constanze

last: Bonifer


title: Intrahepatic immune microenvironment contributes to spontaneous tolerance in pediatric liver transplantation recipients

first: Yuan

last: Liu

address: No. 160 Dongchuan Rd.

institute: Renji Hospital

summary: We carried out a cross-sectional study using clinical data and biospecimens to analyze factors that were associated with immune tolerance after pediatric liver transplantation. Multivariable analysis revealed that peripheral Treg ratio (OR=2.48 (1.55-19.8), p=0.032) and maximum blood EBV-DNA copy (OR=5.53 (1.08-5.67), p=0.008) were associated with the development of tolerance during follow-up, while serum IGM titer (OR=0.73 (0.53-0.99), p=0.046) had a negative relation with tolerance. Histological evaluation indicated no difference on hepatocyte damage, portal inflammation and fibrosis stage between tolerant and non-tolerant recipients. Meanwhile, no deterioration of hepatic pathology was found in recipients with longer follow-up time. Further allograft biopsy transcriptome analysis exhibited distinguished intrahepatic expression patterns between tolerant and non-tolerant recipients. Tolerant allografts were characterized by low expression of cytotoxic and inflammatory genes (like NDUFAF2, MAN1A2, PLEK2, NUDFB4 and FCER1G) and high levels of immune regulatory ones (like SCRIB, MAPK8IP3, TSC2, CHRNA4 and D2HGDH). Especially, immunohistology staining confirmed the upregulated expression of CD39 (ENTPD1) and CD73 (NT5E) in liver sinusoidal endothelial cells and hepatocytes from tolerant allograft, which was associated with increased CD4+ Treg ratio in portal areas.

overall_design: Liver biopsies from pediatric liver transplantation recipients with different immune status were collected and send for RNA sequencing analysis. Then the expression profiles were compared between liver biopsies with diferent immune status.

first: Yongbo

first: Bingran

last: Wang

first: Qiang

last: Xia


title: miR8175 has an effect on glucose metabolism in obese mice

first: Huichen

last: Song

overall_design: Diet-induced obese mice were divided into two groups, and were treated with NC and miR8175 for 6 weeks, respectively. The liver tissues were collected for transcriptome sequencing


title: Selective requirement of 3D genomic organization for the Mdm1-Il22-Ifng locus regulation in initial Th1 cell lineage specification and differentiation [ATAC-Seq]

first: Vijay

last: Nagarajan

address: 10 Center Drive, 10/10N248

department: National Eye Institute

institute: National Institutes Of Health

summary: Eukaryotic DNA fibers are organized into structured subunits in the nucleus, but the extent to which these 3D chromatin architectures influence cytokine expression remains unclear. Here, we investigate the role of dynamic loop formation within the topologically associating domain (TAD) in regulating the expression of two critical cytokines, interferon-gamma (IFN-) and interleukin-22 (IL-22). These cytokine loci are closely located in the genome and are associated with complex enhancer landscapes, which are selectively active in type 1 and type 3 lymphocytes. Using in situ Hi-C, we demonstrate inducible TADs that insulate Ifng and Il22 enhancers during Th1 differentiation. Deleting the boundary of these TADs resulted in imbalanced Th1- and Th17-associated immunity, both in vitro and in vivo. In contrast, this boundary element was dispensable for cytokine regulation in NK cells. Our finding suggest that precise cytokine regulation relies on lineage- and developmental stage-specific interactions of 3D chromatin architectures and enhancer landscapes.

overall_design: We differentiate naive T cells with TCR signaling CD3 and CD28 and cytokines IL-12 ex vivo to Th1 cells in WT and IfngCTCFdel mice, and performed focused Hi-C for 3-D architecture and chromatin interactions, bulk RNA-seq for transcriptomic analysis, in parellel using ATAC-seq and ChIP-seq (p300, rad21, CTCF, H3K4me1, H3K27ac, H3K4me3) for epigenomic profiling. To understand the immune response change in the WT and IfngCTCFdel mice in vivo, we measured gene expression of cells isolated from mice infected by Toxoplasma gondii for three and seven days, and by LCMV for 4 days and 7 days using single cell RNA-seq. We also used whole genome sequencing to evaluate of our mouse model generated by CRISPR/Cas9.

first: Chunhong

first: Hiroyuki

last: Nagashima

first: Nilisha

last: Fernando

first: Victor

last: Bass

first: Jaanam

last: Gopalakrishnan

first: Sadie

last: Signorella

first: Will

last: Montgomery

first: Ai

last: Lim

first: Oliver

last: Harrison

first: Lauren

last: Reich

first: Chen

last: Yao

first: Hong-Wei

last: Sun

first: Stephen

last: Brooks

first: Jiang

last: Kan

first: Vijayaraj

first: Yongbing

last: Zhao

first: Seol

last: Jung

first: Rachael

last: Phillips

first: Yohei

last: Mikami

first: Caleb

last: Lareau

first: Yuka

last: Kanno

first: Dragana

last: Jankovic

first: Martin

last: Aryee

first: Aleksandra

last: Pekowska

first: Yasmine

last: Belkaid

first: John

last: O’Shea

first: Han-Yu

last: Shih


title: Pharmaceutical inhibition of RAS overcomes cytokine mediated resistance to FLT3 inhibition in FLT3-ITD+ AML [DNaseI-seq]

first: Peter

last: Keane

overall_design: DNaseI-Seq of FLT3-ITD primary AML samples before and after treatment with a FLT3 inhibitor

first: Daniel

last: Coleman

last: Cockerill

first: Constanze

last: Bonifer


title: Comparative gene expression profiling analysis of RNA-seq data for U251 control and hnRNPA2B1 knockdown  cells

city: xi'an

first: Liangliang

last: Shen

address: West changle road 169

institute: The fourth military medical university

summary: Gliomas are the most common type of primary brain tumors, accounting for approximately 80% of all malignant brain tumors. The m6A RNA methylation process, mediated by various m6A regulatory genes, has been implicated in promoting the development and progression of tumors. However, the understanding of its involvement in glioma remains limited. Therefore, RNA sequencing (RNA-seq) was performed in U251 cells following hnRNPA2B1 knockdown, as it functions as an oncogene and is one of the m6A reader proteins.

overall_design: Expression profiling analysis of RNA-seq data for U251 control and hnRNPA2B1 knockdown  cells

first: Zhang

last: Juan


title: Pharmaceutical inhibition of RAS overcomes cytokine mediated resistance to FLT3 inhibition in FLT3-ITD+ AML [ChIP-seq]

overall_design: ChIP-Seq of FLT3-ITD cell lines (MV411, MOLM14) targeting cFOS and RUNX1 before and after treatment with FLT3i, RASi, Doxyclin inducible RAS antibody (RAS iDAB), IL3 and untreated


title: Extracellular vesicles from epicardial fat mediate long-distance heart-brain communication and promote atrial fibrillation associated cognitive impairment (EAT exosomal miRNA-seq and hippocampal mRNA-seq)

city: Wuhan

first: wang

last: xuewen

address: 238 Jiefang Road, Wuhan 430060, China

department: Department of Cardiology

institute: Renmin Hospital of Wuhan University

summary: 2 weeks of rapid atrial pacing increased the release of epicardial adipose tissue (EAT) exosomes. The red fluorescence of Ad-CD63-RFP traces the increase of EAT exosomes in the canine hippocampus. RNA Sequencing showed that the differentially expressed genes of cfa-miR-22e in EAT exosomes were significantly increased, and its target gene of IL33 was down-regulated in the hippocampus. Exosomes secreted by EAT in AF model canine penetrate the BBB, and activate hippocampal microglia through cfa-miR-22e/IL33 signaling pathway, which may be related to the increased risk of cognitive impairment in AF.

overall_design: To investigate the effect of atrial fibrillation on cognitive impairment, canines were randomly divided into the sham group, the pacing group. The miRNA was detected from EAT exosomes of canines in the sham group and the pacing group, and the mRNA was detected from hippocampal tissue in the same group of canines. The results of heart and brain sequencing were analyzed jointly

first: Xuewen

last: Wang

first: Yuanjia

last: Ke

first: Zhen

last: Cao

first: Qingyan

last: Zhao


title: Expression data from  OL and OC treated B16F10 cells

city: Tsukuba,

first: Meriem

last: Bejaoui

state: Ibaraki

address: 1 Chome-1-1 Tennodai

country: Japan

institute: University of Tsukuba

summary:
Oleocanthal (OL) and Oleacein (OC) are enriched components in Olive (oil and leaves). However, their effects on skin have not been widely studied compared to Oleuropein (OP). Here, we perfomed global gene expression profiling to screen the potential effects of OL and OC on the skin. Results showed that OL and OC have effects on skin development and keratinocyte differentiation by upregulation of key markers. Furthermore, OL and OC were effectively downregulated several melanogenic genes and it suggests that OL and OC can have a potential effect for pigmentation.
B16F10 were murine melanoma cells line, treated with 5 µM of OL and OC for 24 hours. Microarray gene expression profiling was conducted technical replicates.

overall_design: RNA was extracted using Isogen (Nippon Gene Co. Ltd., Toyama, Japan). The integrity of RNA was quantified using NanoDrop 2000 spectrophotometer (Thermo Scientific, Wilmington, DE, USA). RNA samples were prepared for gene expression profiling analysis with GeneChip® 3' Expression Arrays using 3' IVT PLUS Reagent Kit (Affymetrix Inc., Santa Clara, CA, USA). Two hundred and fifty ng of total RNA from each sample was used to generate amplified and biotinylated complementary RNA (cRNA) from poly (A) RNA in a total RNA sample according to the user manual. IVT Incubation time was 16 hour. GeneAtlas® Hybridization, Wash and Stain Kit was used for hybridizing 3' IVT Array Strips according to the user manual (P/N 08-0306). The mouse genome array strips were hybridized for 16 hours in a 45oC incubator, washed and stained and finally imaging was done with the GeneAtlas Fluidics and Imaging Station.


title: Activation of  the YAP/KLF5 transcriptional cascade in renal tubular cells aggravates kidney injury

city: Hong  Kong

first: YANG

last: LIU

address: Lo Kwee-Seong Integrated Biomedical Sciences  Building, Area 39

department: School of Biomedical Sciences

institute: The Chinese University of Hong  Kong

summary: The Hippo/YAP pathway plays a critical role in early embryonic kidney development, but its functions in the adult kidney are less well understood. Our previous work has demonstrated that tubular YAP activation induced by double knockout of the upstream Hippo kinases Mst1 and Mst2 (Mst1/2 dKO) promotes tubular injury and renal inflammation under basal conditions. However, the importance of tubular YAP activation remains to be established in injured kidneys in which many other injurious pathways are simultaneously activated. Several secreted factors were found to be increased by YAP in tubular cells, but how the transcriptional network is altered by YAP  is largely unknown.  Here, we show that tubular YAP was already activated at 6 h after unilateral ureteral obstruction (UUO). Tubular YAP deficiency greatly attenuated tubular cell over-proliferation, tubular injury and renal inflammation induced by UUO or cisplatin. RNA-Seq, ChIP and luciferase assay revealed that YAP promoted the transcription of the transcription factor KLF5 whereas no interaction between YAP and KLF5 was observed. Consistently, the elevated expression of KLF5 and its target genes in Mst1/2 dKO or UUO kidneys was blocked by ablation of Yap in tubular cells. Inhibition of KLF5 prevented tubular cell over-proliferation, tubular injury and renal inflammation in Mst1/2 dKO kidneys. Therefore, our results demonstrate that tubular YAP is a key player in kidney injury. YAP and KLF5 form a transcriptional cascade, in which tubular YAP activation induced by kidney injury promotes KLF5 transcription. Activation of this cascade induces tubular cell over-proliferation, tubular injury and renal inflammation

overall_design: HK-2 cells cultured in DMEM/F12 containing 1% FBS underwent electrotransfection with GFP or Yap and Taz plasmids. 5 h after electrotransfection, total RNA was extracted. RNA sequencing (RNA-seq) was performed on an Illumina Nova Seq 6000 System (Novogene Co., Ltd.).

first: Yang

last: Liu

first: Yu

first: Chunhua

last: Xu

last: Zhang

first: Jinzhong

last: Qin

first: Kingston

middle: K

last: Mak

first: Hui-Yao

last: Lan

first: Li

last: Huang

first: Zhihua

last: Zheng

first: Yin

last: Xia


title: Rewiring the Mitochondrial Electron Transport Chain Enhances Tumor Immunogenicity

city: La Jolla

first: Mannix

last: Burns

email: mburns@salk.edu, mannixburns@gmail.com

state: CA

address: 10010 N Torrey Pines Rd

institute: Salk Institute

summary: Although tumor growth requires the mitochondrial electron transport chain (ETC), the relative contribution of Complex I (CI) and II (CII), the gatekeepers for initiating electron flow, remains unclear. Here, we report that loss of CII, but not CI, reduces melanoma tumor growth by increasing antigen presentation and T cell-mediated killing. This is driven by succinate-mediated transcriptional and epigenetic activation of major histocompatibility complex I-antigen processing and presentation (MHC-APP) genes that is independent of interferon signaling. Furthermore, knock-out of MCJ, to promote electron entry preferentially via CI, provides proof-of-concept of ETC rewiring to achieve anti-tumor responses without side effects associated with an overall reduction in mitochondrial respiration in non-cancer cells. Our results hold therapeutic potential for tumors that have reduced MHC-APP expression, a common mechanism of cancer immunoevasion.

overall_design: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for the histone modifications H3K4me3 and H3K36me3 in YUMM1.7 cells treated with DMSO, 3-NPA, or 3-NPA + aKG, as well as inputs.

first: Kailash

last: Mangalhara

first: Gerald

last: Shadel

first: Diana

last: Hargreaves


title: Pharmaceutical inhibition of RAS overcomes cytokine mediated resistance to FLT3 inhibition in FLT3-ITD+ AML [ATAC-seq]

first: Peter

last: Keane

overall_design: ATAC-Seq of FLT3-ITD primary AML samples, and FLT3-ITD+ cell lines (MOLM14, MV411) before and after treatment with FLT3 inhibitors, RAS inhibitors and IL3 with replicates

first: Daniel

last: Coleman

last: Cockerill

first: Constanze

last: Bonifer


title: Pharmaceutical inhibition of RAS overcomes cytokine mediated resistance to FLT3 inhibition in FLT3-ITD+ AML

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

overall_design: Refer to individual Series


title: Understanding differential heat tolerance of the threatened coral Orbicella faveolata from transplanted reef sites in the Florida Keys using gene network analysis

city: Miammi

first: Catalina

last: Aguilar

state: Florida

address: 4600 Rickenbacker Causeway

department: Rosenstiel School of Marine, Atmospheric & Earth Science

institute: University of Miami

summary: Twelve inshore and six offshore colonies were reciprocally transplanted during 1 year (July 2017- July 2018) at Florida Keys (location). After this period samples were collected from the field and brought to the Experimental Reef Laboratory facilities (RSMAS, Miami) to be acclimated to 30C during 7 days in six aquaria. Three aquaria were keep under initial conditions for the duration of the experiment (30C) and three aquaria had the temperature increased everyday during 7 days to a final temperature of 32C. A total of 56 samples were collected for RNAseq after 6 days of the temperature treatment and stored at -80C.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for the coral Orbicella faveolata at different temperature treatments.

first: Ian

last: Enochs

first: Leah

last: Chomiak

first: Graham

last: Kolodziej

first: Andrew

last: Baker

first: Derek

last: Manzello


title: Combining anti-PD1 and vorinostat improves anti-tumor treatment in IDH-mutant brain tumors

first: Yeung

last: Sivannn

address: Dongan Road

institute: Fudan University

summary: Enhancer RNA (eRNA) is critical element with highly specific pattern in regulatory network across infiltrated immune cells. Herein we developed eRNA immunotherapy signature (eRIS) based on these eRNAs which significantly connected with anti-tumor immune cells. The eRIS was highly correlated with objective response rate (ORR) to immune checkpoint blockade (ICB) treatment, and was significantly increased in these patients who benefit from ICB treatment. By integrating with pharmacogenomics datasets, we screened hundreds of eRIS associated anti-cancer drugs, which showed potential in improving immunotherapy with cancer type or subtype-specific specific manner. We further characterized one drug, the HDAC inhibitor vorinostat, in isocitrate dehydrogenase mutant gliomas, and found Combining vorinostat with anti-PD-1 could decrease tumor size and increase survival time in vivo by enhancing abundance of anti-tumor immune cells. We further provided eRIS markers which showed strong capacity of eRIS in predicting immunotherapy response in clinical samples or animal models. Our study revealed the potential utility of eRIS to improve immunotherapy response by identifying combinational drugs, that provide novel insights to benefit patients in certain cancer or subtypes.

overall_design: To investigate the efficiency of combining anti-PD1 and vorinostat, we established the LGG IDH-mutant tumor model in mouse by stereotactic injection with the 1:1 mixture of DF-1 cells expressing R132H-mutant IDH and DF-1 cells expressing PDGFB into nesin-TVA mice.

first: Chenyang

last: Zhang


title: Genome-wide Mapping of Endogenous G-quadruplexes Unravels Their Roles in Enhancer Architecture across Human Cell Lines

city: Xi'an

first: Yue

last: Hou

state: Shaanxi

address: No.28, West Xianning Road, Xi'an, Shaanxi, 710049,P.R. China

institute: Xi'an JiaoTong University

summary: We found that G4 structures assist to shape the nucleosome positioning and nucleosome depleted regions on enhancers. Moreover, many transcription factor (TF) clusters tend to co-target G4 on enhancers, leading to widespread enhancer transcriptional signals. These TFs further influenced the chromatin interactions between G4 enhancers and their target genes. Additionally, G4 enhancers harbored significantly higher enrichment of expression quantitative trait locus than typical enhancers, suggesting G4 enhancers displayed more enhancer regulatory activity.

overall_design: We used BG4 ChIP-seq method to target all endogenous G4 structures in the LnCap cell line and described the relationship between enhancers and G4s.

first: Xiaorong

last: Zhou

first: Sheng

last: Li

first: Tie-Lin

last: Yang


title: PCB126 Modifies the Murine Hepatic Transcriptome and Metallome to Promote Alcohol-associated Liver Disease Pathogenesis

city: Louisville

first: Eric

middle: Christian

last: Rouchka

state: Kentucky

address: 522 East Gray Street

department: Biochemistry and Molecular Genetics

institute: University of Louisville

summary: Background: Environmental pollutants, including polychlorinated biphenyls (PCBs) have been shown to alter and promote the development of alcohol-associated liver disease (ALD). Our group recently demonstrated that PCB126 promoted steatosis, hepatomegaly, and modulated intermediary metabolism in an ALD rodent model. Objectives: To better understand how PCB126 promoted ALD, the current study adopts transcriptomic and metallomic approaches to identify mechanistic pathways involved in this promotion. Methods: Briefly, male C57BL/6J mice were exposed to 0.2 mg/kg PCB126 or corn oil vehicle prior to ethanol feeding in the chronic-binge model. Liver tissues were collected for RNA sequencing and ICP-MS metals quantification. Results: PCB126 uniquely modified the transcriptome in EtOH-fed mice in terms of variance. EtOH feeding alone resulting in >4000 differentially expressed genes (DEGs) and PCB126 exposure resulted in more DEGs in the EtOH-fed group over the pair-fed group. Top gene ontology (GO) biological processes indicated ‘peptidyl tyrosine modifications’ and GO molecular function processes showed a loss of ‘metal, and ion, and zinc binding’. Western blot analysis depicted that the JAK2-STAT5 signaling axis was disrupted by the enhanced loss of phosphorylated JAK2 in EtOH+PCB126 mice. Quantified liver essential metal levels were overall depleted by EtOH feeding, and potassium, magnesium, cobalt, and zinc were further decreased by PCB126. Discussion: The results suggests that phosphorylation and metal binding are disrupted in EtOH+PCB126 mice, implying that evolutionarily conserved homeostatic signaling mechanisms are modified by pollutant exposure in EtOH-fed mice. The loss of phosphorylation and essential metals are two suggestive modes of action that may explain the promotion of disease by PCB126 in ALD.

overall_design: C57BL/6J mice were orally gavaged 0.2 mg/kg polychlorinated biphenyl 126 (PCB 126). Mice were then placed on the chronic-binge (ten-plus-one) alcohol (ethanol) feeding model using the Lieber-DeCarli Diet. Mice were initially allowed to acclimate to the diet over 5 days where mice were given 1 day of 0% ethanol, 2 days of 2% ethanol, and 2 days of 4% ethanol. Mice were then fed a 5% ethanol diet for 10 days. The following day (11th day - binge) mice were orally gavaged 5g/kg ethanol, followed by euthanasia and tissue collection. This study is an exact repeat of our characterization study previously published (PMID: 36377258)

first: Tyler

last: Gripshover

first: Banrida

last: Wahlang

first: Kimberly

middle: Z

last: Head

first: Jianzhu

last: Luo

first: Oluwanifemi

last: Bolatimi

first: Melissa

last: Smith

first: Julia

middle: H

last: Chariker

first: Lu

last: Cai

first: Jason

last: Xu

first: Matthew

last: Cave


title: Role of LY6E subpopulation on myeloma cell growth

city: Little Rock

first: Intawat

last: Nookaew

address: 4301 W Markham St

department: Department of Biomedical Informatics

institute: University of Arkansas for Medical Sciences

summary: Overexpression of LY6E in myeloma cells is associated with poor prognostic. We studied the molecular properties of LY6E+ and LY6E- myeloma cells from the same patients and assessed their growth potential

overall_design: CD138-selected myeloma cells from 5 patients were sorted basted on cell surface LY6E and then the LY6E+ and LY6E- cells were subjected to global gene expression profiling

first: Shmuel

last: Yaccoby


title: Identification of C9orf72 as a potential target of osteoarthritis via STING/NF-κB axis by integrating bioinformatics and experiments

city: Hangzhou

first: Yutao

last: Zhu

address: East Qing Chun Road

institute: Sir Run Run Shaw Hospital, Zhejiang University School of Medicine,

summary: RNA-sequence analysis demonstrated ECM degradation and inflammation activation in C28/I2 cells with C9orf72 knockdown

overall_design: Examination of different expression genes in C28/I2 cells with or without C9orf72 knockdown

first: Zhijun

last: Hu

first: Honghai

last: Song

first: Nengfeng

last: Yu


title: Immune cell transcriptional programs severe allergic airway inflammation

city: Columbus

first: Rodney

last: Britt

state: Oh

address: 575 Childrens Crossroad

department: Center for Perinatal Research

institute: Nationwide Children's Hospital

summary: Innate and adpative immune cells play an integral role in asthma pathogenesis. We performed single cell RNA sequencing on CD45+ immune cells isolated from PBS or c-di-GMP + mixed allergen challenged mice.

overall_design: CD45+ cell were isolated from the mouse lung following intranasal PBS or c-di-GMP + mixed allergen exposures 3X per week for 7 weeks.  Two mouse lungs given the same treatments were pooled following digestion.

last: Britt Jr

first: Joshua

last: Walum

first: Mireia

last: Guerau-de-Arellano

first: Stephanie

last: Amici

first: Brandon

middle: W

last: Lewis


title: Proteasome gene expression is controlled by the coordinated functions of multiple transcription factors

city: Haifa

first: Tamar

last: Lahav

address: Zor

department: Biology

country: Israel

institute: Technion

summary: Proteasome activity is crucial for cellular integrity, but how tissues adjust proteasome content in response to catabolic stimuli is uncertain. Here, we demonstrate that transcriptional coordination by multiple transcription factors is required to increase proteasome content and activate proteolysis in catabolic states. Using denervated mouse muscle as a model system for accelerated proteolysis in vivo, we reveal that a two-phase transcriptional program activates genes encoding proteasome subunits and assembly chaperones to boost an increase in proteasome content. Initially, gene induction is necessary to maintain basal proteasome levels, and in a more delayed phase (7-10 d after denervation) it stimulates proteasome assembly to meet cellular demand for excessive proteolysis. Intriguingly, the transcription factors PAX4 and α-PALNRF-1 control the expression of proteasome among other genes in a combinatorial manner, driving cellular adaptation to muscle denervation. Consequently, PAX4 and α-PALNRF-1 represent new therapeutic targets to inhibit proteolysis in catabolic diseases (e.g. type-2 diabetes, cancer).

overall_design: WT and transgenic animals are subjected to muscle denervation and gene expression analyses are performed on their muscles.

first: Shenhav

last: Cohen

first: Yael

last: Mandel-Gutfreund


title: H2A.Z histone variants facilitate HDACi-dependent removal of H3.3K27M mutant protein in paediatric high-grade glioma cells

city: Gdansk

first: Jakub

last: Mieczkowski

address: Debinki 12

country: Poland

institute: Medical University of Gdansk

summary: Diffuse intrinsic pontine gliomas (DIPG) are paediatric malignant gliomas developing  in the brainstem, where resection is unattainable, leaving palliative radiotherapy as the major standard of care. Patients with DIPG have dismal prognosis of 9-12 months of survival and currently there is no effective therapy. Over 80% of DIPGs harbour a mutation in histone 3 (H3.3 or H3.1) resulting in a lysine to methionine substitution (H3K27M). H3K27M causes global epigenetic alterations (a loss of H3K27 trimethylation and an increase H3K27 acetylation) resulting in aberrant gene expression. To date, no therapeutic strategy exists to suppress the levels of oncogenic H3K27M.   We show that pan-HDAC inhibitors (HDACi) lead to the temporary but significant reduction in the H3.3K27M protein (up to 80%) in multiple glioma cell lines expressing the H3.3K27M histone variant, without changes in the H3F3A mRNA expression. The H3.3K27M occupancy at the chromatin is greatly reduced upon HDACi (SB939) treatment, as shown by ChIPseq analysis. H3.3K27M loss is most striking at SB939-upregulated genes suggesting re-expression of repressed genes. Certain H3K27M-dependent genes become downregulated in response to SB939 treatment. We discover that the SB939-mediated loss of H3.3K27M is partially blocked by a lysosomal inhibitor chloroquine. Moreover, the loss of H3.3K27M is facilitated by co-occurrence of H2A.Z, as evidenced by the knock-down of H2A.Z histone isoforms. ChIPseq analysis confirms the occupancy of H3.3K27M and H2A.Z at the same SB939-inducible genes. Altogether, we provide new insight into disease-specific mechanism of HDAC inhibition and demonstrate pharmacological modulation of the oncogenic H3.3K27M protein levels. These findings open a new possibility to directly target the H3.3K27M oncohistone, which may be exploited in future therapies.

overall_design: Comparative gene expression profiling analysis of RNA-seq and ChIP-seq data for DIPG H3.3K27M cells treated with DMSO (control) or SB9393 (HDACi).

first: Katarzyna

last: Leszczynska


title: Effecto of ROS (H2O2) on undifferentiated NSC

city: Solna

first: susanne

last: neumann

address: Solnavägen 1

country: Sweden

institute: Karolinska Instituet

summary: Realease of reactiv oxigen species, such as H2O2, has been observed during inflammatory processes but is also a physiological side product of metabolism. We have observed that differentiation of neural progenitor cells (NPC) is affected by H2O2 exposure. We here asses the transcriptional drivers of the phenotypical changes NPCs undergo during differentiation in response to H2O2.

overall_design: 2 timepoints (1h or 8h exposure to 100µM H2O2) with 4 biological replicates per timepoint,  and Control samples 4 biological replicates. Paired samples( 1h, 8h and contrl for each of the 4 used animals

first: Susanne

last: Neumann

first: Ewoud

last: Ewing

first: Ruxandra

last: Covacu

first: Lou

last: Brundin


title: The phosphorylation of FOXA1-S331 is indispensable for FOXA1-AR dependent cistrome [ATAC-seq]

city: Shanghai

first: Ni

last: Li

address: 320 Yueyang Road, Shanghai, 200025 P.R. China

institute: Institute of Health Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences

summary: To define the function of FOXA1-S331 phosphorylation, we substituted S331 in both FOXA1 alleles for alanine in C4-2 cells via CRISPR/Cas9-based gene editing, thereby generating phosphorylation incompetent FOXA1S331A cells. We directly assessed the consequences of phospho-incompetent FOXA1S331A mutation on the transcription profile, chromatin deposition of FOXA1, AR, H3K27ac and chromatin accessibility.

overall_design: Examination of chromatin accessibility in WT and FOXA1S331A C4-2 cells.

first: Jiacheng

last: Guo

first: Jun

last: Qin


title: The phosphorylation of FOXA1-S331 is indispensable for FOXA1-AR dependent cistrome [Cut&Tag]

overall_design: Chromatin immunoprecipitation DNA-sequencing (CUT&Tag-seq) for FOXA1, AR well as the histone modification H3K27ac in WT and FOXA1S331A C4-2 cells.


title: The phosphorylation of FOXA1-S331 is indispensable for FOXA1-AR dependent cistrome.


title: VSV infected mouse peritoneal macrophages with treatment of DiFMOC-G

first: Qihang

last: Zhao

address: 800 xiangyin road

institute: National laboratory of medical immunology

summary: Transcriptome analysis of peritoneal macrophages infected with VSV (12h) and with or without pre-treatment of DiFMOC-G for 12 hours .

overall_design: To analyze variation of gene expression by comparing group of DMSO with group of DiFMOC-G.

first: Pin

last: Wang

first: Zhengdong

last: Yang


title: Momordicine I Suppresses Glioma Growth by Promoting Apoptosis and Impairing Mitochondrial Oxidative Phosphorylation

city: Taipei

first: Yung Lung

last: Chang

address: Rm. 7309, 7F., No.161, Sec. 6, Minquan E. Rd., Neihu Dist.

department: Biochemistry

institute: National Defense Medical Center

summary: RNA microarray was performed from glioma cell LN229 and GBM8401 that were treated with Momordicine (10 microM) for 48hr in comparison to DMSO vehicle control

overall_design: To study the growth inhibition of glioma cells in response to Momordicine treatment, total 8 samples were prepared from glioma cells LN229 and GBM8401 for RNA extraction and hybridization on OneArray® Gene Microarrays. glioma cells treated with Momordicine or  DMSO, which is taken as vehicle control samples (control).

first: Yung-Lung

first: Chia-Kuang

last: Tsai


title: Transcription factor ZIC2 regulates tumorigenic phenotypes in epithelial ovarian cancer in a context-dependent manner

city: Edmonton

first: Laura

middle: Jiyoung

last: Lee

state: Alberta

address: 5-120 Katz Group Centre

department: Oncology

country: Canada

institute: University of Alberta

summary: Transcription factor ZIC2 plays a pro-tumorigenic role in several human cancers. Herein, we demonstrate that elevated ZIC2 expression was associated with lower overall and post-progression survival of epithelial ovarian cancer (EOC) patients. Knockout of ZIC2 in EOC cells attenuated tumorigenic phenotypes in vitro and in vivo, indicating a pro-tumorigenic role for ZIC2 in EOC. On the other hand, however, overexpression of ZIC2 in EOC cells that do not express endogenous ZIC2 promoted cell migration and sphere formation, but inhibited cell growth and colony formation in vitro and tumor growth in vivo, indicating a context-dependent function for ZIC2 in EOC. Transcriptomic study showed that ZIC2-regulated genes were involved in multiple biological processes and signaling pathways associated with tumor progression and that ZIC2 regulated common or distinct genes in ZIC2 knockout and overexpression models, which explains the consistency and discrepancy in ZIC2 functions observed in the two models. In conclusion, our findings reveal a context-dependent role for ZIC2 in regulating tumorigenic phenotypes in EOC, providing evidence that ZIC2 can be a potential therapeutic target for EOCs that express a high level of ZIC2.

overall_design: Gene expression profiling analysis of RNA-seq data for SKOV3 ZIC2 WT, SKOV3 ZIC2 KO, OVCAR3 EV, and OVCAR3 ZIC2 OE

first: Huachen

last: Chen

middle: J

first: Lynne

last: Postovit

first: YangXin

last: Fu


title: RNA sequencing (RNA-seq) of PQBP1 knockdown in ovarian cancer cells

city: Jinan

first: Xihan

last: Liu

state: Shandong

address: Wenhuaxi Road #44

institute: Shandong University

summary:
To investigate the comprehensive function of PQBP1 in the regulation of RNA splicing, we established Dox-inducible PQBP1 knockdown HEY cell line.
We then performed gene expression profiling analysis using data obtained from RNA-seq of PQBP1 knockdown and control HEY cells (three biological replications of each sample).

overall_design: Comparative gene expression profiling analysis of RNA-seq data for Dox-inducible PQBP1 knockdown HEY cells (shNC, shPQBP1). The assay was performed on three biological triplicates.

first: Zhaojian


title: Long-read nanopore sequencing (Nanopore-seq) of PQBP1 knockdown in ovarian cancer cells

summary:
To investigate the comprehensive function of PQBP1 in the regulation of RNA splicing, we established Dox-inducible PQBP1 knockdown HEY cell line.
We then performed transcript expression profiling analysis using data obtained from long-read nanopore-seq of PQBP1 knockdown and control HEY cells (three biological replications of each sample).

overall_design: Comparative transcript expression profiling analysis of Nanopore-seq data for Dox-inducible PQBP1 knockdown HEY cells (shNC, shPQBP1). The assay was performed on three biological triplicates.


title: Comparative transcriptome analysis of iron-overaccumulating Arabidopsis genotypes uncover novel putative regulators of systemic and retrograde signaling

first: Louis

last: Grillet

address: Agricultural Chemistry Building No. 2, Rm. 209A No. 1, Sec. 4, Roosevelt Rd.

institute: National Taiwan University

summary: Maintaining iron homeostasis requires a precise orchestration of cellular uptake, trafficking through mesophyll cells, translocation via xylem and phloem, and uptake of iron by roots adjusted to the demand of sink organs by systemic signals. Plants defective in the iron transporter OPT3 in the leaves behave as if they were constitutively iron deficient and accumulate toxic iron levels in their leaves. IRONMAN (IMA) genes encode peptides that trigger iron remobilization and uptake by inhibiting the ubiquitin ligase BRUTUS. Ectopic expression of IMA genes also causes iron accumulation. This study aims at bridging the knowledge gap of the mechanisms operating between OPT3-transported iron and the activation of IMA genes, and between phloem-localized IMAs and the activation of iron uptake genes in the epidermis. A small subset of genes was found to be shared among the three iron-accumulating genotypes and iron-deficient control plants. Root expression profiles were more strongly correlated that those of shoots, confirming a predominant function in the regulation of root processes by IMAs and OPT3. The largest overlap was observed between opt3-2 and wild-type plants. IMA1 Ox and IMA3 Ox lined showed a surprisingly small overlap except for the iron-related genes, suggesting distinct physiological functions. A small subset of genes was consistently differentially expressed in all the genotypes, including genes involved in root iron uptake and ROS detoxification. The small suite of differentially expressed genes common to all genotypes under investigation constitute potential novel regulators of cellular iron homeostasis.

overall_design: The study includes the RNAseq-based transcriptome profiling of the shoots and roots of the Fe-accumulating genotypes opt3-2, IMA1 Ox, IMA3 Ox and a transgenic control line expressing EYFP under the control of a 35s promoter. The plants were grown in vitro, on plates containing ES medium, under control and Fe-deficient conditions. Fe deficiency was achieved by transferring the plants for 3 days on medium without Fe and supplemented with 300 µM ferrozine.

first: Wolfgang

last: Schmidt


title: Transcriptomic profile of  M0 and M1 phenotype macrophages.

city: Wuhan

first: Chen

last: zhang

state: Hubei

address: Jiefang road 1037

institute: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

summary: Bone marrow derived macrophages from 8-week-old C57BL/6 mice was stimulated ex vivo with or without LPS and IFN-γ for 24 hours. Each group has two replicates.

overall_design: Bone marrow cells were collected, washed, and resuspended in complete DMEM media containing 1% penicillin–streptomycin and 10% FBS to a concentration of 1 × 106 cells/ml. Bone marrow cells were differentiated into macrophages for 7 days in the presence of 20ng/ml recombinant murine MCSF in complete medium, with complete media changes every 48 hours. On day 6, macrophages were cultured for 24 hours at 37°C and 5% CO2 in complete media containing 20ng/ml recombinant MCSF alone (M0) or in the media containing 20 ng/mL IFN-γ and 100 ng/mL LPS (M1).

first: Zhang

first: Jiahong

last: Xia

first: Jie

last: Wu


title: SpyTag-based CLIP (SpyCLIP) sequencing of PQBP1 in ovarian cancer cells

summary: Dysregulated expression of splicing factors has important roles in cancer development and progression. However, it remains a major challenge to identify the cancer-specific splicing variants. Here we demonstrated that splicing factor PQBP1 is commonly overexpressed in high-grade serous ovarian carcinoma (HGSOC) and high level of PQBP1 is associated with poor prognosis. To gain global insights into PQBP1-RNA binding property, RNA immunoprecipitation sequencing (RIP-seq) and SpyTag-based CLIP (SpyCLIP) were performed to analysis the interaction between PQBP1 and the target RNA.

overall_design: SpyTag-based CLIP (SpyCLIP) sequencing for PQBP1 in HEY cells.


title: RiboSeq and mSeq of two yeast strains

city: Bern

first: Robert

last: Rauscher

state: Bern

address: Freiestrasse 3

institute: University of Bern

summary: We report on how the absence of expansion segment 7S from the yeast ribosome alters A-site occupancy along transcripts. This has consequence for local translation rates and protein fidelity.

overall_design: Examination of total and ribosome protected mRNA in wild-type and ΔES7S yeast yJD1045 strain depleted of genomic rDNA. rRNA is exclusively plasmid borne.

first: Cristian

last: Eggers

first: Lyudmila

last: Dimitrova-Paternoga

first: Vaishnavi

last: Shankar

first: Marina

last: Cristodero

first: Helge

last: Paternoga

first: Daniel

middle: N

last: Wilson

first: Sebastian

last: Leidel

first: Norbert

last: Polacek


title: NUDT21 alters glioma migration through differential alternative polyadenylation of LAMC1

city: Houston

first: Venkata

middle: Soumith

last: Jonnakuti

state: TX

address: 2255 Braeswood Park Drive

institute: Baylor College of Medicine

summary: We identified LAMC1 as a critical NUDT21 target involved in several core glioma-driving signaling pathways. qRT-PCR analysis confirmed that NUDT21-knockdown in GBM cells resulted in the preferred usage of the proximal C/PAS of LAMC1. Furthermore, functional studies revealed that NUDT21-knockdown-induced 3’UTR shortening of LAMC1 was sufficient to induce translational gain, as LAMC1 was upregulated in these cells compared to their respective controls. Additionally, we demonstrated that primary glial cells recapitulated this phenomenon. We also further dissected the miRNA-mediated mechanism by which LAMC1 expression was regulated by showing that NUDT21 knockdown in glioma cells directed the 3’UTR shortening of LAMC1, removing binding sites for miR-124/506 and consequently inducing LAMC1 expression. Remarkably, we reported that the knockdown of NUDT21 significantly promoted GBM cell migration and that co-depletion of LAMC1 and NUDT21 abrogated this effect. Lastly, we observed that LAMC1 3’UTR shortening predicted poor prognosis of low- and high-grade glioma patients from The Cancer Genome Atlas.

overall_design: Anti-NUDT21 and scramble shRNA-infected LN229 / U251 human gliablastoma cell lines mRNA 3' end sequencing profiles generated by deep sequencing, in triplicate, using Illumina Nextseq 550.

middle: S

first: Ping

last: Ji

first: Yeping

last: Gao

first: Ai

last: Lin

first: Yuan

last: Chu

first: Nathan

last: Elrod

first: Kai-Lieh

last: Huang

first: Wei

last: Li

first: Hari

last: Yalamanchili

first: Eric

last: Wagner


title: Chemerin triggers migration of a CD8 T cell subset with natural killer cell functions

city: Palo Alto

first: Melissa

last: LaJevic

address: 3801 Miranda Ave

institute: PAVIR

summary: We identified subsets of human CD28- effector CD8 T cells, of CCR7- CD45RO+ effector memory (EM) and CCR7- CD45RO- effector memory RA (EMRA) phenotypes, that express the chemerin receptor CMKLR1 and bind chemerin via the receptor. This study investigates differential gene expression between the chemerin binding and nonbinding human CD8 EMRA T cell subsets.

overall_design: Human blood CD8 EMRA T cells (CD8+ CD45RO- CCR7-) were sorted based on the presence or absence of chemerin binding and analyzed using Ultra-low input RNAseq. Three biological replicates were included in the analysis.

first: Romain

last: Ballet

first: Noelle

last: Mullin

first: Kevin

last: Brulois

first: Ying

first: Muhammad

last: Saeed

first: Russell

last: Pachynski

first: Elizabeth

first: Eugene

last: Butcher

first: Brian

last: Zabel


title: RNA immunoprecipitation sequencing (RIP-seq) of PQBP1 in ovarian cancer cells

first: Xihan

last: Liu

overall_design: RNA immunoprecipitation sequencing (RIP-seq) for PQBP1 in HEY cells.

first: Zhaojian


title: Multi-omics analysis reveals altered lipid metabolism in the skin of high fat diet-fed mice of atopic dermatitis

city: DAEJEON

first: Jeeyoun

last: jung

address: Yuseong daero 1672

country: South Korea

institute: Korea institute of Oriental Medicine

summary: To identify the obesity-induced exacerbating mechanisms of AD symptoms by multi-omics analysis. Then, we demonstrated the therapeutic effect of GHJGS in circulating lipid profiles.

overall_design: For diet-induced obesity, mice were fed a HF diet (60 kcal% fat, D12492, Research Diets, New Brunswick, NJ) for up to 4 weeks before the induction of AD. Sham groups were fed a normal autoclave rodent chow (38057, Purina Korea, Seoul, Korea). After the induction of obesity for 4 weeks, (1) the sham [normal diet + vehicle + distilled water (DW)]; (2) AD [normal diet + 2,4-dinitrochlorobenzene (DNCB) + DW]; (3) HF+AD (HF diet + DNCB + DW) (4) HF+AD+GHJGS; HF diet + DNCB+ GHJGS 617 mg/kg/day) for 6 weeks. To induce AD, dorsal skin was applied three times a week with 0.5% DNCB mixed in acetone/olive oil (3:1).

last: Jung

first: You

last: Ahn


title: Selective requirement of 3D genomic organization for the Mdm1-Il22-Ifng locus regulation in initial Th1 cell lineage specification and differentiation

city: Bethesda

first: Vijay

last: Nagarajan

address: 10 Center Drive, 10/10N248

institute: National Institutes Of Health

summary: Eukaryotic DNA fibers are organized into structured subunits in the nucleus, but the extent to which these 3D chromatin architectures influence cytokine expression remains unclear. Here, we investigate the role of dynamic loop formation within the topologically associating domain (TAD) in regulating the expression of two critical cytokines, interferon-gamma (IFN-) and interleukin-22 (IL-22). These cytokine loci are closely located in the genome and are associated with complex enhancer landscapes, which are selectively active in type 1 and type 3 lymphocytes. Using in situ Hi-C, we demonstrate inducible TADs that insulate Ifng and Il22 enhancers during Th1 differentiation. Deleting the boundary of these TADs resulted in imbalanced Th1- and Th17-associated immunity, both in vitro and in vivo. In contrast, this boundary element was dispensable for cytokine regulation in NK cells. Our finding suggest that precise cytokine regulation relies on lineage- and developmental stage-specific interactions of 3D chromatin architectures and enhancer landscapes.

overall_design: We differentiate naive T cells with TCR signaling CD3 and CD28 and cytokines IL-12 ex vivo to Th1 cells in WT and IfngCTCFdel mice, and performed focused Hi-C for 3-D architecture and chromatin interactions, bulk RNA-seq for transcriptomic analysis, in parellel using ATAC-seq and ChIP-seq (p300, rad21, CTCF, H3K4me1, H3K27ac, H3K4me3) for epigenomic profiling. To understand the immune response change in the WT and IfngCTCFdel mice in vivo, we measured gene expression of cells isolated from mice infected by Toxoplasma gondii for three and seven days, and by LCMV for 4 days and 7 days using single cell RNA-seq. We also used whole genome sequencing to evaluate of our mouse model generated by CRISPR/Cas9.

first: Chunhong

first: Hiroyuki

last: Nagashima

first: Nilisha

last: Fernando

first: Victor

last: Bass

first: Jaanam

last: Gopalakrishnan

first: Sadie

last: Signorella

first: Will

last: Montgomery

first: Ai Ing

last: Lim

first: Oliver

last: Harrison

first: Lauren

last: Reich

first: Chen

last: Yao

first: Hong-Wei

last: Sun

first: Stephen

last: Brooks

first: Jiang

last: Kan

first: Vijayaraj

first: Yongbing

last: Zhao

first: Seol Kyoung

first: Rachael

last: Phillips

first: Yohei

last: Mikami

first: Caleb

last: Lareau

first: Yuka

last: Kanno

first: Dragana

last: Jankovic

first: Martin

last: Aryee

first: Aleksandra

last: Pekowska

first: Yasmine

last: Belkaid

first: John

last: O’Shea

first: Han-Yu

last: Shih


title: The phosphorylation of FOXA1-S331 is indispensable for FOXA1-AR dependent cistrome [RNA-seq]

first: Ni

last: Li

state: Shanghai

overall_design: Comparative gene expression profiling analysis of RNA-seq data for C4-2 cells and its mutiaon derivative (FOXA1S331A).

first: Jiacheng

last: Guo

first: Jun

last: Qin


first: Vijay

last: Nagarajan

first: Chunhong

last: Liu

first: Hiroyuki

last: Nagashima

first: Nilisha

last: Fernando

first: Victor

last: Bass

first: Jaanam

last: Gopalakrishnan

first: Sadie

last: Signorella

first: Will

last: Montgomery

first: Ai Ing

last: Lim

first: Oliver

last: Harrison

first: Lauren

last: Reich

first: Chen

last: Yao

first: Hong-Wei

last: Sun

first: Stephen

first: Jiang

last: Jung


title: PABPC1 RIP-Seq and RNA-Sequence Analysis of Si-LINC00882 in 231 Cells

city: Jiaxing

first: Huadong

last: Ni

address: zhonghuan nan road 1882

institute: Department of Anesthesiology and Pain Research Center, The Affiliated Hospital of Jiaxing University

summary: RNA-seq was used to analyze the differential expression of mRNAs between si-LINC00882 and si-NC-LINC00882 231 cells.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for si-LINC00882  and RIP-PABPC1 in 231 cells.

first: Hai-ting

first: Sen

first: Xiang-yu

first: Guo-hao

last: Zhang


title: Transcriptional profiling of human colon “cancer stem cell” populations (EpCAM+, CD44+, CD166+) following in vivo exposure to irinotecan.

city: Nutley

first: Piero

last: Dalerba

state: NJ

address: 111 Ideation Way

department: Center for Discovery and Innovation (CDI)

institute: Hackensack Meridian Health

summary:
In human colon cancer, the malignant component of tumor tissues often contains multiple sub-types of cancer cells, whose transcriptional profiles and surface marker phenotypes correspond to those of the epithelial lineages that are found in normal colonic crypts (e.g., goblet cells, enterocytes, LGR5+ columnar basal cells). Among those various sub-types of malignant cells, those characterized by a surface marker phenotype that is characteristic of epithelial stem/progenitor cells residing at the bottom of colonic crypts (EpCAM+, CD44+, CD166+) are enriched in cells with "cancer stem cell" (CSC) properties, such as self-renewal (i.e., the capacity to sustain the formation of new tumors upon serial xeno-transplantation in immune-deficient animals) and multi-lineage differentiation (i.e., the capacity to sustain the formation of other cell-types, thus reconstituting the heterogeneous population of the parent tumors from which they have been isolated). Cell populations with "cancer stem cell" (CSC) properties are known to be preferentially resistant to several cytotoxic agents used in conventional chemotherapy, but the molecular mechanisms underpinning this property remain poorly understood.

In this dataset, we report the analysis by gene-expression microarrays of the transcriptional profile of two sub-populations of human colon cancer cells: 1) cells with a "bottom-of-the-crypt" phenotype (EpCAM+, CD44+, CD166+), which are known to be enriched in "cancer stem cells" (CSCs); and 2) cells with a "top-of-the-crypt" phenotype (EpCAM+, CD44neg, CD166neg), which are known to be non-tumorigenic upon xeno-transplantation in immune-deficient mice. The two populations were purified in parallel by fluorescence activated cell sorting (FACS), starting from solid tumors established by sub-cutaneous (s.c.) engraftment in immune-deficient mice of a patient-derived xenograft (PDX) line representative of a moderately differentiated (G2) primary colon carcinoma. To identify genes whose expression is modulated by in vivo exposure to chemotherapy (and thus potentially involved in the mechanistic regulation of chemo-resistance), we compared the transcriptional profile of cells purified from tumors that were exposed to 4 weeks of in vivo treatment with either irinotecan (CPT-11) or a placebo control (saline solution).

overall_design: The two sub-populations of colon cancer cells analyzed in this study (EpCAM+/CD44+/CD166+, EpCAM+/CD44neg/CD166neg) were isolated in parallel by fluorescence activated cell sorting (FACS), starting from solid tumors that were established by sub-cutaneous (s.c.) xeno-transplantation into adult, female, NOD/SCID/IL2Rg-/- (NSG) immune-deficient mice (The Jackson Laboratory: stock #005557) of a patient-derived xenograft (PDX) line representative of a moderately differentiated (G2) primary colon carcinoma (PDX-COLON-8), and following in vivo treatment of tumor-bearing mice with either irinotecan (50 ug/g, once weekly x 4 weeks, i.p.) or a placebo (1 ml saline solution, once weekly x 4 weeks, i.p.). The two populations of cancer cells were sorted in parallel from 4 independent tumors (2 from animals treated with irinotecan + 2 from animals treated with saline solution), for a total of 8 samples, which included 4 replicates for each of the two main orthogonal variables (cell phenotype vs. in vivo treatment). Tumor tissues were dissociated into single-cell suspensions by mechanical mincing into small fragments, followed by enzymatic digestion using DNAse-I (100 units/ml) and collagenase-III (200 units/ml), according to previously published protocols (Dalerba et al., PNAS, 104:10158-10163, 2007; Dalerba et al., Nature Biotechnology, 29:1120-1127, 2011). Single-cell suspensions were stained with monoclonal antibodies directed against differentially expressed surface antigens (human cells: EpCAM, CD44, CD166; mouse cells: H2-Kd) and sorted using a FACSAria-II machine (Becton Dickinson), after exclusion of dead cells (DAPI+), cell doublets (serial gating based on FSC-A vs. FSC-H and SSC-A vs. SSC-W profiles) and mouse cells (H2-Kd+).

first: Junichi

last: Matsubara

first: Yong

middle: F

last: Li

first: Debashis

last: Sahoo


first: Vijay

last: Nagarajan

first: Chunhong

last: Liu

first: Hiroyuki

last: Nagashima

first: Nilisha

last: Fernando

first: Victor

first: Jaanam

first: Sadie

first: Will

last: Brooks

last: Kan

first: Vijayaraj

first: Yongbing

last: Zhao

first: Seol Kyoung

first: Rachael

last: Phillips

first: Yohei

last: Mikami

first: Caleb

last: Lareau

first: Yuka

last: Kanno

first: Dragana

last: Jankovic

first: Martin

last: Aryee

first: Aleksandra

last: Pekowska

first: Yasmine

last: Belkaid

first: John

last: O’Shea

first: Han-Yu

last: Shih


title: RNA-seq analysis of lung tissues from Kiss1r+/+, Kiss1rflox/+, and Kiss1rflox/flox mice with KrasG12D mutation

city: seoul

first: seoyeon

last: lee

state: State...

address: space21, preventive medicine, room 861

institute: KyungHee University

summary: Our aim is to investigate the transcriptional changes in Kiss1r+/+, Kiss1rflox/+, and Kiss1rflox/flox mice with Kras mutation during early stage of lung tumorigenesis using RNA-seq.

overall_design: Lungs of Kiss1r+/+, Kiss1rflox/+, and Kiss1rflox/flox mice at 5 weeks after induction of KrasG12D using Ad5-CMV-cre were isolated for RNA-seq.

first: SeoYeon

last: Lee

first: Sunggook

last: Cho


title: Nucleus Ambiguus RNA Expression in Pink1-/- and Wildtype Rats

city: Madison

first: Cynthia

last: Kelm-Nelson

state: WI

address: 1300 University Avenue, 416 Medical Sciences Center

department: Surgery

institute: University of Wisconsin- Madiso

summary: Parkinson’s disease (PD) is a progressive degenerative disease. Behaviorally, voice deficits including soft monotone speech appear early and are present in 90% of individuals with PD. However, the pathology, at the level of the nucleus ambiguus, mediating voice deficits is unknown. RNA sequencing was used to examine nucleus ambiguus differential gene expression in male Pink1-/- rats compared to age-matched wildtype controls.

overall_design: Comparative gene expression profiling analysis using data obtained from the RNA-sequencing between the two genotypes (Pink1-/- and WT) in both male and female rats.

first: Stephen

middle: C

last: Gammie


title: Next generation sequencing for miRNA profile of blood sample of goiter rat model treated by quemeiteng granule

city: Chengdu

first: Yang

last: Li

address: No.37 Guoxue Alley, Wuhou District,

institute: West China Hospital of Sichuan University

summary: MicroRNAs play important roles in the regulatory processes of occurrence and progression of goiter. In the present study, whole transcriptome sequencing analysis was applied to investigate the expression profiles of miRNAs. After comparing blood samples of propylthiouracil (PTU)-induced goiter model blood samples and quemeiteng granule (QMTG) treated groups, 1 miRNA was found to be differentially expressed. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to investigate the potential functions of the mRNAs. Our study proved QMTG relieves goiter by suppressing thyroid angiogenesis through miR-217-5p targeting of FGF2 regulating ERK pathway.

overall_design: Examination of miRNA profile in blood sample of six groups.

first: Wen

last: Yang

first: Hui

last: Wu


first: Vijay

last: Nagarajan

state: Maryland


title: The chromatin remodeling factor Arid1a cooperates with Jun/Fos to promote osteoclastogenesis by epigenetically upregulating Siglec15 expression

city: hangzhou

first: Zhaoming

last: Ye

address: 88 jiefang road

institute: The Second Affiliated Hospital, Zhejiang University School of Medicine

summary: Osteoporosis is characterized by an imbalance between osteoclast-mediated bone resorption and osteoblast-related bone formation, particularly increased osteoclastogenesis. However, the mechanisms by which epigenetic factors regulate osteoclast precursor differentiation during osteoclastogenesis remain poorly understood. Here, we show that the specific knockout of the chromatin remodeling factor Arid1a in bone marrow?derived macrophages (BMDMs) results in increased bone mass. The loss of Arid1a in BMDM inhibits cell?cell fusion and maturation of osteoclast precursors, thereby suppressing osteoclast differentiation. Mechanistically, Arid1a increases the chromatin access in the gene promoter region of sialic acid?binding Ig-like lectin 15 (Siglec15) by transcription factor Jun/Fos, which results in the upregulation of Siglec15 and promotion of osteoclast differentiation. However, the loss of Arid1a reprograms the chromatin structure to restrict Siglec15 expression in osteoclast precursors, thereby inhibiting BMDM differentiation into mature osteoclasts. Deleting Arid1a after ovariectomy (a model for postmenopausal bone loss) alleviated bone loss and maintained bone mass. In summary, epigenetic reprogramming mediated by Arid1a loss suppresses osteoclast differentiation and may serve as a promising therapeutic strategy for treating bone loss diseases.

overall_design: Comparison of gene expression profiles and chromatin accessibility during osteoblast differentiation after Arid1a knockout. *Submitters did not provide the processed data for ATAC-Seq and CUT&Tag.

first: Yongxing

last: Zhang

first: Hangxiang

last: Sun

first: Fei

last: Huang

first: Li

last: Shen


title: Glomerular transcriptomics predicts outcome and identifies therapeutic strategies for patients with assumed benign IgA nephropathy

city: Bergen

first: Philipp

last: Strauss

address: Haukeland Universitetssykehus Laboratoriebygget, 7. etg. Heis øst

country: Norway

institute: University of Bergen

summary:
Background:  In a previous study of patients with assumed benign IgA nephropathy (IgAN), we have shown that 18.6% develop a progressive clinical course, which was not predicted by any known clinical nor histopathological parameters (Knoop 2017). We aim to differentiate between future progressors and non-progressors with assumed benign IgAN by using glomerular transcriptomics from diagnostic kidney biopsies and to investigate whether this can identify drugs to be used in those patients.
Methods: We included adult progressors (n=15) and patients with clinical remission (non-progressors, n=21) from our previously reported IgAN cohort. Glomerular cross-sections were obtained through laser-capture microdissection from 10µm archival kidney biopsy sections for mRNA sequencing, using the SMARTer Stranded Total RNA-Seq kit – Pico Input Mammalian (Clontech Laboratories, California, USA). Key results were validated in external cohorts and on the protein level with immunohistochemistry in the discovery cohort and an internal validation cohort. We also compared our transcriptomic findings with an external genome-wide association study (GWAS) dataset (Kiryluk 2021).
Results: For the statistical analyses, we studied 8 progressors and 9 non-progressors. Based on the 1,240 differentially expressed glomerular genes from the initial kidney biopsies, we were able to identify future IgAN progressors and non-progressors using a two-component classifier. The classifier predicted disease progression with 88% accuracy, 75% sensitivity and 100% specificity (AUC=0.875), more accurate than the recommended International IgAN Prediction Tool in this specific patient cohort. Among our differentially expressed genes, 10 were also found in the GWAS dataset (Kiryluk 2021). We identified 45 drug targets in the DrugBank database, including angiotensinogen, a target of sparsentan, currently investigated as therapy in IgAN (NCT03762850 and NCT04663204). The findings on upregulation of angiotensinogen, which was independent of blood pressure, were validated in an internal IgAN validation cohort. Interestingly, complement activation did not play a major role in our data.
Our work suggests that LXR, FXR and macrophage activation pathways   could be critically involved in the inhibition of the progression of low-risk ccRCC. Furthermore, a 10-component classifier could support an early identification of apparently low-risk ccRCC patients.

overall_design:
Glomerular mRNA sequencing from diagnostic kidney biopsies from patients with assumed benign IgAN can differentiate between future progressors and non-progressors at the time of diagnosis, on average 21.6 years before progressive disease is documented.
-------------------------------------------
Authors state "Due to Norwegian Data Protection Law we cannot upload the FASTQ raw data."
*** Raw data is to be made available through dbGaP (controlled access) due to patient privacy concerns****

first: Mariell

last: Rivedal

first: Havard

last: Mikkelsen

first: Hans-Peter

last: Marti

first: Thomas

last: Knoop

first: Rune

last: Bjørneklett

first: Yngvar

last: Haaskjold

first: Jessica

last: Furriol

first: Sabine

last: Leh

first: Flavia

last: Paunas

first: Janka

last: Bábíčková

first: Andreas

last: Scherer

first: Oystein

last: Eikrem


title: Accumulating Oxidative DNA Damage in Reconstituting T-cells is Associated with Disease Relapse and Inferior Survival Following Allo-SCT

city: Würzburg 97074

first: Chunguang

last: Liang

state: Bayern

address: Bioinformatik, Biozentrum, Uni Würzburg, Am Hubland

department: Bioinformatics

country: Germany

institute: Biozentrum

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

overall_design: Refer to individual Series


title: Accumulating Oxidative DNA Damage in Reconstituting T-cells is Associated with Disease Relapse and Inferior Survival Following Allo-SCT [RNAseq in vivo]

summary: Oxidative T-cell DNA damage impacts GVL

overall_design: Comparative gene expression profiling analysis of RNA-seq data for T-cells of allogeneic transplanted patients with high oxidative DNA damage (n = 5) to T-cells of allogeneic transplanted patients with low oxidative DNA damage (n =5)

first: Franziska

last: Karl

first: R

last: Böttcher-Loschinski

first: D

last: Mougiakakos


title: Accumulating Oxidative DNA Damage in Reconstituting T-cells is Associated with Disease Relapse and Inferior Survival Following Allo-SCT [RNAseq in vitro]

summary: Oxidative T-cell DNA damage impacts GVL

overall_design: Comparative gene expression profiling analysis of RNA-seq data for human T-cells treated with H2O2 to induce oxidative damage to untreated controls (5 donors)


title: Transcriptomic profiles of testis from hindlimb unloaded mice treated with 4-phenylbutyrate

city: Sharjah

first: Amir

middle: Ali

last: Khan

address: Emirates of Sharjah

department: Department of Applied Biology

country: United Arab Emirates

institute: University of Sharjah

summary: Transcriptomic profiles of Testis of hindlimb unloaded mice treated with vehicle or 4-phenylbutyrate (4-PBA)

overall_design: 16 weeks old, male C57bl6/J mice were hindlimb-unloaded (HU) for three weeks, and treated with vehicle or 4-phenylbutyrate to prevent testicular pathalogy.   The testis from the ground mice were used as control.

first: Rizwan

last: Qaisar

first: Anu

last: Ranade


title: Analysis of small extracellular vesicle derived miRNAs using high through-put miRNA sequencing

city: Shanghai

first: Chen

last: Xu

address: No, 800, Rd. Xiangyin

institute: The Second Military Medical University

summary: To gain insight into the microRNA expression profile of small extracellular vesicle derived from different cell types and to verify their mechanism, we utilized the miRNA sequencing technology to analyze the miRNA profiles of different human cell derived small extracellular vesicle

overall_design: We collect the small extracellular vesicles from the supernatant of several widely used stem cell types and osteoblst using ultracentrifugation method. The small extracellular vesicles were then extracted for small RNAs to perform high through-put sequencing

first: Huajiang

last: Chen

first: Wen

last: Yuan


title: Next Generation Sequencing  Quantitative Analysis of TEAD Palmitoylation Inhibitor TM2 in NCI-H226 cells

city: Charlestown

first: Yang

last: Sun

state: MA

address: 149 13th Street, CBRC 3050E

department: CBRC

institute: Massachusetts General Hospital

summary:
Purpose: The goal of this study is to understand the signaling pathway alteration in NCI-H226 cells treated with new TEAD autopalmitoylation inhibitor TM2,  and to further validate TEAD inhibitor for specifity in TEAD-YAP interuption.
Methods: Mesothelioma cell line NCI-H226 was chosen to be treated with TEAD palmitoylation inhibitor TM2 at 1μM for 24 hours. Total RNA was isolated for the analysis. RNA samples were sent to Novogen for library construction, RNA sequencing and raw data process.  Conclusions: Our study privides gene expression profiling evidence to validate our TEAD palmitoylation inhibitor TM2 as specific small molecule to block TEAD transcriptional activity in mesothelioma cells.

overall_design: Comparative gene expression profiling analysis of RNA-seq data forNCI-H226 cells treated with vehicle control and TEAD autopalmitoylation inhibitor TM2.

first: Xu

last: Wu

first: Lu

last: Hu


title: Maternal Schistosomiasis 14 days post immunization draining lymph node V(D)J scRNAseq

city: Salt Lake City

first: Keke

middle: Celeste

last: Fairfax

state: UT

address: 15 N Medical Drive East

department: Pathology

institute: University of Utah

summary: We performed V(D)J scRNA sequencing to find transcriptional and B cell receptor repertoire differences in the germinal center of the draining lymph node of mice born to mothers chronically infected with Schistosoma mansoni. Cite-seq was used to help identify antigen specific cells.

overall_design: Cells sorted were DAPI-CD19+GL-7+CD95+ from the draining lymph node (popliteal) of mice born to S. mansoni infected and control mothers 14 days after Tetanus/Diphtheria vaccination into the footpad. After sorting, cells were stained with anti-Tetanus toxin-FITC and an anti-FITC oligonucleotide-tagged antibody. Lymph nodes from at least 3 mice were pooled before sorting. Cells were loaded into the 10X Chromium instrument according to the manufacturer's directions. Females from infected mothers were collected and sequenced separately than other samples.

first: Lisa

last: Gibbs

first: Juan

middle: M

last: Oviedo


title: Analysis by RNA-seq of the transcriptional profile of three sub-populations of mouse colon epithelial cells (Lgr5+ columnar basal cells, goblet cells, enterocytes).

first: Piero

last: Dalerba

summary: In this dataset, we report the analysis by RNA-sequencing (RNA-seq) of the transcriptional profile of three sub-populations of epithelial cells contained in the mouse colonic epithelium: 1) Epcam+/Cd44+/Kit-neg cells, which correspond to a population of epithelial cells located at the bottom of colonic crypts and enriched in Lgr5+ columnar basal cells (CBCs); 2) Epcam+/Cd44+/Kit+ cells, which correspond to a population of epithelial cells located at the bottom of colonic crypts and enriched in goblet cells; 3) Epcam+/Cd44-neg/Cd66-high cells, which correspond to a population of epithelial cells located at the top of colonic crypts and enriched in mature enterocytes (Rothenberg et al., Gastroenterology, 142:1195-1205, 2012).

overall_design: All three populations included in the study (Epcam+/Cd44+/Kit-neg, Epcam+/Cd44+/Kit+, Epcam+/Cd44-neg/Cd66-high) were sorted by fluorescence activated cell sorting (FACS), starting from adult colonic tissues of female C57BL/6J mice (The Jackson Laboratory: stock #000664). For each of the three populations, three independent replicates were generated, each sorted from an independent mouse, for a total of 9 samples, representative of 3 independent mice. Colonic crypts were detached from colon tissues using EDTA (5 mM) and then dissociated into single-cell suspensions using DNAse-I (100 units/ml) and Collagenase-III (200 units/ml). Single-cell suspensions were stained with monoclonal antibodies against differentially expressed surface antigens (Epcam, Cd44, Kit, Cd66a, Cd3, Cd16/Cd32, Cd31, Cd45) and sorted using a FACSAria-III machine (Becton Dickinson), after exclusion of dead cells (DAPI+), cell doublets (serial gating based on FSC-A vs. FSC-H and SSC-A vs. SSC-W profiles) and cells of non-epithelial lineages (Cd3+, Cd16/Cd32+, Cd31+, Cd45+).

first: Junko

last: Mukohyama

first: Debashis

last: Sahoo


title: Maternal Schistosomiasis Bone Marrow B Cell V(D)J scRNAseq

summary: We performed V(D)J scRNA sequencing to find transcriptional and B cell receptor repertoire differences in maturing B cells of mice born to mothers chronically infected with Schistosoma mansoni. Cite-seq was used to help identify subpopulations.

overall_design: Bone marrow cells were purified from bone marrow from the femur of mice born to S. mansoni infected and control mothers using a FACs Aria. Sorted cells were DAPI-CD3-CD4-CD8a-CD11b-CD11c-GR-1-Ter119-CD19+B220+IgD+IgM+/-. After sorting, cells were stained with the cell surface protein IgD oligonucleotide-tagged antibody to perform CITE-sequencing. Bone marrow from at least 3 mice were pooled before sorting. Cells were loaded into the 10X Genomics Chromium instrument according to the manufacturer's directions.


title: Single Cell sequencing analysis of AT1/AT2 cells from wildtype mouse, AT1-Cdc42 knockout mouse, and left bronchial ligation model

city: Philadelphia

first: Michael

middle: Patrick

last: Morley

state: PA

address: 3400 Civic Center Blvd, Bldg 421

department: Penn Cardiovascular Institute

institute: Perelman School of Medicine at the University of Pennsylvania

summary: The goal of this study was to compare wildtype adult lung epithelium to epithelium from Cdc42 AT1-KO mice and mice after left bronchial ligation model.

overall_design: Two samples of adult mouse epithelial cells, three samples of adult Hopx-CreERT2; Cdc42 KO lineage traced mice, and three samples of Hopx-CreERT2 lineage traced mice after left bronchial ligation were pooled respectively for library preparation.

first: Kazu

last: Shiraishi

middle: P

first: Edward

middle: E

last: Morrisey


title: Transcriptome sequencing of HepG2 cells upon treatment of Butyrolactone I (PQY09) or derivatives (PQY23_1) butenolide compounds for exploring the targets of PQYs to further study the pharmacological activities

city: Guangzhou

first: Lan

last: Tang

state: Guangdong

address: 1838  Guangzhou North Ave,

department: School of Pharmaceutical Science

institute: Southern Medical University

summary:
Transcriptome sequencing (RNA-Seq) of HepG2 cells upon treatment of the 50μM Butyrolactone I (PQY09) or derivatives (PQY23_1) butenolide compounds isolated from marine-derived fungi or DMSO(0.1%) as blank contrast for exploring the targets of PQYs to further study the pharmacological activities
Butenolide, a mycotoxin produced by several toxigenic Fusarium species, fre-quently invades many important grains, and evokes a broad spectrum of toxic effects. But several butenolide derivatives, especially the well-known compound butyrolactone I, have been reported to show diverse biological activities, including an-ti-inflammatory , antibacterial , antiviral, antitumor, and α-/β-glucosidase inhibitory activities. So in order to investigate the other effect of PQYs and toxicity target, we  used the second-generation transcriptome sequencing(RNA-seq) to determine the expression changes of each gene in HepG2 cells.

overall_design: mRNA profiles of  HepG2 cells upon treatment of the 50μM PQY09 or PQY23_1 or DMSO(0.1%) were generated by deep sequencing, using illumina Novaseq™ 6000


title: Lamin B1 ChIP-seq analysis of alveolar type 1 and type 2 cells.

summary: The goal of this study was to compare lamina-associated chromatin between alveolar type 1 and type 2 cells.

overall_design: AT1 cells and AT2 cells were sorted from AT1 reporter Hopx-EGFP mice or AT2 reporter Sftpc-EGFP mice.

first: Parisha

last: Shah

first: Rajan

last: Jain


title: Mechanotransduction mediated by cyclical respiratory motion maintains lung alveolar epithelial cell fate


title: Maternal and Chronic Schistosoma Infection Bone Marrow B cell scRNAseq

summary: We performed scRNA sequencing to find transcriptional differences in early B cell populations in the bone marrow of mice born to mothers chronically infected with Schistosoma mansoni compared to their mothers. Cite-seq was used to help identify cluster types using surface protein markers.

overall_design: Hematopoietic stem and progenitor cells and B cells were purified from bone marrow from the femur of mice born to S. mansoni infected and control mothers using a FACs Aria. Sorted cells were DAPI-CD3-CD4-CD8a-CD11b-CD11c-GR-1-Ter119-CD19-. CD19 was used in place of B220 to enrich for pre-pro B cells, but the antibody was ineffective, allowing for all B cell types to be sorted. After sorting, cells were stained with the cell surface proteins CD127, CD124, CD117, Sca-1, CD16/32 and CD138 with oligonucleotide-tagged antibodies to perform CITE-sequencing. Bone marrow from at least 3 mice were pooled before sorting. Cells were loaded into the BD Rhapsody instrument according to the manufacturer's directions.


title: High-throughput mapping of 2'-O-methylation in Trypanosoma brucei poly(A) RNAs using RibOxi-seq

city: Durham

first: Christopher

middle: L

last: Holley

state: NC

address: 2301 Erwin Rd

institute: Duke University

summary: In this study we used RibOxi-seq to identify 2’-O-methylation (Nm) present on mRNAs in single nucleotide resolution. Our analysis identified hundreds of Nm sites in mRNAs, predominantly in CDS and 3’ UTR.

overall_design: Trypanosoma brucei procyclic form was used to extract total RNA. The RNA was then polyA enriched before going through RibOxi-seq for 2'-O-methylation profiling

first: Yinzhou

last: Zhu

first: K

last: Rajan

first: Shulamit

last: Michaeli


title: Mapping of 2'-O-methylation in Trypanosoma brucei small RNAs using RibOxi-seq

type: Methylation profiling by high throughput sequencing

summary: In this study we combined small RNA isolation from post-ribosomal supernatant with RibOxi-seq to identify 2’-O-methylation (Nm) in single nucleotide resolution. Our analysis identified ~49 Nm sites in tRNA, snRNAs, snoRNAs, 7SL RNA and vtRNA.

overall_design: Trypanosoma brucei procyclic form was used to extract small RNAs. The RNA was then underwent RibOxi-seq for 2'-O-methylation profiling protocol with modifications