title: Gene expression profiling in miR-574-5p knockdown HeLa cells and the controls

city: Xiamen

first: James

middle: Yunqing

last: Yang

state: Fujian

address: Xiang'an South Road

department: School of Life Sciences

institute: Xiamen University

summary:
To profile gene expression in human HeLa cells follwing the knockdown of miR-574-5p, as compared to control HeLa cells
Gene ontology and clustering analyses revealed that the differentially-expressed genes were highly enriched for the immune system and its related signal transduction pathways.

overall_design: Total RNA from each sample was quantified by the NanoDrop ND-1000 and RNA integrity was assessed by standard denaturing agarose gel electrophoresis. Total RNA of each sample was used for labeling and array hybridization as the following steps: 1) Reverse transcription with by Invitrogen Superscript ds-cDNA synthesis kit; 2) ds-cDNA labeling with NimbleGen one-color DNA labeling kit; 3) Array hybridization using the NimbleGen Hybridization System and followed by washing with the NimbleGen wash buffer kit; 4) Array scanning using the Axon GenePix 4000B microarray scanner (Molecular Devices Corporation).  Scanned images (TIFF format) were then imported into NimbleScan software (version 2.5) for grid alignment and expression data analysis. Expression data were normalized through quantile normalization and the Robust Multichip Average (RMA) algorithm included in the NimbleScan software. The Probe level (*_norm_RMA.pair) files and Gene level (*_RMA.calls) files were generated after normalization. The 6 gene level files were imported into Agilent GeneSpring GX software (version 11.5.1) for further analysis. Genes that have values greater than or equal to lower cut-off: 50.0 in that at least 3 out of 6 samples (“All Targets Value”) were chosen for data analysis. Significant differentially expressed genes were identified through Volcano Plot filtering.

first: Yu

last: Luo


title: RNA-Seq analyses in miR-574-5p-transfected mouse splenocytes

status: Public on Jul 04 2023

country: China

type: Expression profiling by high throughput sequencing

summary: RNA profiling by RNA-Seq analyses showed that in comparison with the control Dotap-treated cells, miR-574-5p transfection for 24 h resulted in significant up-regulation of 277 genes and down-regulation of 80 genes by at least 2-fold in the miR-574-5p-transfected splenocytes. Gene ontology and pathway enrichment analyses showed that the 277 significantly up-regulated genes in miR-574-5p-transfected cells were highly enriched and clustered in pathways associated with interferon and cytokine signaling, antiviral mechanisms, translesion synthesis and autoimmunity .

overall_design: Mouse splenocytes were isolated from three 8-wk old female B6.WT mice with each sample divided in to two equivalent aliquots, one for Dotap-only and one for Dotap-PS-miR-574-5p transfection. Splenocytes were cultured in DMEM supplemented with 10% FBS, 2mM L-glutamine and 100 IU/ml penicillin and 100 μg/ml streptomycin for 4 h. Subsequently , cultured splenocytes were transfected with Dotap-only or Dotap-PS-miR-574-5p (Dotap-only-1, -2 and -3 and Dotap-miRNA-1, -2 and -3) at the concentration of 10 μg/ml. After 24 h of incubation, cells were harvested for RNA extraction and an alyses.

middle: Y

first: Dan

last: Song


title: Gene Expression Profiling Unveils the Temporal Dynamics of CIGB-300-Regulated Transcriptome in AML Cells

city: La Habana

first: Dania

last: Vázquez-Blomquist

department: System Biology

country: Cuba

institute: Center for Genetic Engineering and Biotechnology

summary:
Transcriptomic profile study comparing human acute leukemia derived cell lines HL-60  and OCI-AML3 treated with the antitumoral peptide CIGB-300 at 30min and at 3h.
CIGB-300 is an antitumoral peptide that blocks CK2 phospho-acceptor sites on their substrates but it also binds to CK2α catalytic subunit. This peptide has demonstrated their antiproliferative effects on different models including acute leukemia cells and also their antitumoral action in animal models and in clinical assays. We performed a Clariom S HT  microarray gene RNA expression profiling to study the molecular events supporting the anti-leukemic effect of CIGB-300 peptide on HL-60 and OCI-AML3 cell lines.

overall_design: Eight groups or conditions with three biological replicates each, including HL60 and OCI-AML3 cells: treated with CIGB-300 for 30min and 3h and time-matched control untreated group.

first: Daniel

last: Palenzuela


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool2_h1930001_MTG

status: Public on Jul 05 2023

city: La Jolla

first: Joseph

middle: R

last: Ecker

state: CA

address: 10010 North Torrey Pines Road

department: Genomic Analysis Laboratory

country: USA

institute: HHMI-Salk-Institute

type: Methylation profiling by high throughput sequencing

summary: Illustrating the cellular architecture of the human brain is critical to understanding its diverse functions and complex animal behaviors. Single nucleus methylation sequencing was applied to regions of human brains. we identified distinct cell clusters and formed them in a hierarchical taxonomy. These clusters include known primary brain cell types and possible sub-types. We use these data to identify the epigenomic characteristics and to define specific regulatory elements for each cell cluster.

overall_design: Apply snmC-seq3 to brain regions to identify epigenomic landcape of the adult human brains

first: Wei

last: Tian

first: Anna

last: Bartlett

first: Hanqing

last: Liu

first: Jordan

last: Altshul

first: Rosa

last: Gomez Castanon

last: Nery

first: Huaming

last: Chen


title: Transcriptomic profiling of the developing rabbit's lung

city: Parma

first: Ilaria

last: Minato

address: Parco Area delle Scienze 23/a

country: Italy

institute: Università di Parma

summary: Preterm infants are delivered during vulnerable stages of lung development at late canalicular, saccular, or early alveolar phases according to their degree of prematurity. Consequently, they often require medical interventions, especially to support their respiratory system. Preterm birth and post-natal oxygen and mechanical ventilation support can alter programmed patterns of fetal lung development, leading to the instauration of chronic lung diseases. The most significant pulmonary complication of preterm birth is bronchopulmonary dysplasia (BPD).  The aim of this study is to delve into the translational power of rabbits as a suitable model of neonatal chronic lung diseases, characterizing the physiological rabbit lung development through the application of histological, transcriptomic, and proteomic analyses on perinatal rabbit lung samples, investigating the impact of preterm birth and its relevance on BPD modeling.

overall_design: QuantSeq 3' mRNA-Seq (Lexogen) of lung samples collected from rabbit pups at different prenatal and postnatal ages

first: Barbara

last: Montanini

first: Danilo

last: Tatoni

first: Simona

last: Cantarella

first: Simone

last: Ottonello

first: Matteo

last: Storti

first: Francesca

last: Ricci

first: Fabrizio

last: Salomone


title: Expression analysis of C. elegans DAF-15 neuronal AID worms

city: Nanjing

first: Xiao

last: Zang

address: 12 Xuefu Rd, Pukou

institute: Nanjing University

summary: Investigation of whole genome gene expression level changes in C. elegans DAF-15 neuronal AID worms under 5-Ph-IAA treatment. This project contains 8 samples (4 treated by etoh and 4 treated by 5-Ph-IAA) of RNA-seq data.

overall_design: RNA-Seq analysis of C. elegans DAF-15 neuronal AID worms treated with etoh (4 replicates) or 5-Ph-IAA (4 replicates).

first: Di

first: Qi

last: Wang


title: Effect of CDK7 inhibitor on MYCN-amplified retinoblastoma

city: Chengdu

first: Hanyue

last: Xu

state: Sichuan

address: Guoxuexiang street

institute: West China Hospital, Sichuan University

summary: Retinoblastoma (RB) is a common malignancy that primarily affects pediatric populations. Although a well-known cause of RB is RB1 mutation, MYCN amplification can also lead to the disease, which is a poor prognosis factor. Studies conducted in various tumor types have shown that MYCN inhibition is an effective approach to impede tumor growth. Various indirect approaches have been developed to overcome the difficulty of directly targeting MYCN, such as modulating the super enhancer (SE) upstream of MYCN. The drug used in this study to treat MYCN-amplified RB was THZ1, a CDK7 inhibitor that can effectively suppress transcription by interfering with the activity of SEs. The study findings confirmed the anticancer activity of THZ1 against RB in both in vitro and in vivo experiments. Therapy with THZ1 was found to affect numerous genes in RB according to the RNA-seq analysis. Moreover, the gene expression changes induced by THZ1 treatment were enriched in ribosome, endocytosis, cell cycle, apoptosis, etc. Furthermore, the combined analysis of ChIP-Seq and RNA-seq data suggested a potential role of SEs in regulating the expression of critical transcription factors, such as MYCN, OTX2, and SOX4. Moreover, ChIP‒qPCR experiments were conducted to confirm the interaction between MYCN and SEs. In conclusion, THZ1 caused substantial changes in gene transcription in RB, resulting in inhibited cell proliferation, interference with the cell cycle, and increased apoptosis. The efficacy of THZ1 is positively correlated with the degree of MYCN amplification and is likely exerted by interfering with MYCN upstream SEs.

overall_design: To explore the effect of THZ1 on gene transcription in RB cells, we performed RNA-seq assay on two types of RB cells (Y79 and WERI-Rb-1) after 12h of THZ1 (50nM) treatment, and three biological samples were repeated in each group.

first: Lirong

last: Xiao

first: Naihong

last: Yan

first: Ming

last: Zhang


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool15_h1930002_ACC

first: Joseph

last: Ecker

first: Wei

last: Tian

first: Anna

last: Bartlett

first: Hanqing

last: Liu

first: Jordan

last: Altshul

first: Rosa

last: Gomez Castanon


title: NPRC deletion mitigated atherosclerosis by inhibiting oxidative stress, inflammation and apoptosis in ApoE knockout mice

city: Jinan

first: Cheng

last: cheng

address: Qilu Hospital, Shandong University, No.107, Wen Hua Xi Road, Jinan, Shandong, 250012, P.R. China

institute: Qilu Hospital of Shandong University

summary: ApoE-/-mice were fed chow or Western diet for 12 weeks and NPRC expression was significantly increased in the aortic tissues of Western diet-fed mice. Systemic NPRC knockout mice were crossed with ApoE-/- mice to generate ApoE-/-NPRC-/- mice, and NPRC deletion resulted in a significant decrease in the size and instability of aortic atherosclerotic lesions in ApoE-/-NPRC-/- versus ApoE-/- mice.

overall_design: aortas from 5 ApoE-/- mice and 3 ApoE-/-NPRC-/- were subjected to RNA sequencing

first: Yun

first: Jianmin

last: Yang

last: Cheng


title: The ATAC-seq of SiHa, KOE6E7SiHa, H8, HFF

city: Shenzhen

first: sheng

last: zhong

address: The Xinhu Road 1333

institute: The Sourthern Medical University

type: Genome binding/occupancy profiling by high throughput sequencing

summary:
To Observe the area of open chromatin in the different state of cervical epithelial cell and states to find related transcription factors
We then performed gene expression profiling analysis using data obtained from RNA-seq of 2 different cells

overall_design: By comparing normal, immortalized human cervical epithelial cells, cervical cancer cells,  and after knockout cervical cancer cells using ATAC-seq.

first: Sheng

last: Zhong

first: Xiaona

last: Chen


title: Improved genome annotation of the fungal wheat pathogen Zymoseptoria tritici IPO323 using Iso-Seq and RNA-Seq data

city: Palaiseau

first: Nicolas

last: Lapalu

address: 22 place de l'agronomie

department: SPE

country: France

institute: INRAE

summary: To reannotate the genome of Zymoseptoria tritici IPO323, RNA-Seq and Iso-Seq runs were performed on different growth media to provide new source of evidence for gene model predictors. New gene models were predicted and combined with existing annotation releases. Finally, selection of best gene models was done by congruence with evidence data like transcript assembled from RNA-Seq, Iso-Seq cDNA and fungal proteins from databases.

overall_design: RNA-seq and Iso-seq on wheat pathogen with different growth medias

first: Gabriel

last: Scaliet

first: Marc-Henri

last: Lebrun


title: Transcriptome sequencing analysis reveals enhanced immune and inflammatory responses in canine pyometra

city: Guangzhou

first: Ren-Wei

last: Su

state: Guangdong

address: 483 Wushan Road

department: Histology and Embryology

institute: South China Agricultural University

summary: To investigate the potential regulatory mechanism of pyogenesis in dogs, we conducted transcriptome sequencing analysis on the uterus of pyogenesis dogs and healthy dogs, and the results showed that there were 11812 differentially expressed genes in pyogenesis dogs compared with healthy dogs, among which 7086 genes were up-regulated in utero and 4726 genes were down-regulated. And most of these genes are involved in immune and inflammatory responses.

overall_design: Comparative analysis of gene expression profiles of RNA-SEQ data from normal and pyometric dog uterus.

first: Renwei


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool11_h1930001_ACC

first: Joseph

last: Nery

first: Huaming


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool7_h1930002_V2

last: Ecker

first: Wei

first: Anna


title: A Micro-evolutionary Change in Target Binding Sites as a Key Determinant of Ultrabithorax Function in Drosophila

city: Cambridge

first: Soumen

last: Khan

address: Babraham Hall

department: Epigenetics

country: United Kingdom

institute: Babraham Institute

summary: We investigated the transcriptional profile in Drosophila wing and haltere imaginal discs to identify differentialy expressed genes between the two tissues.

overall_design: Whole RNA was isolated from wing and haltere imaginal discs dissected from Drosophila L3 larvae and libraries prepared using NEBNext® UltraTM Directional RNA Library Prep Kit. Sequencing was carried out on Illumina Hiseq platform using 150*2 paired end chemistry. All experiments were carried out on three independnt biological replicates. edgeR was used to identify differentially expressed genes.

first: LS

last: Shashidhara


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool14_h1930002_A46

last: Tian

last: Bartlett

first: Hanqing

last: Liu

first: Jordan

first: Rosa


title: Epigenome analysis of hiPSC-based tumour models II

city: Magdeburg

first: Ulf

last: Kahlert

address: Leipziger Str 44

country: Germany

institute: Otto-vo-Guericke University

summary: Generation of in vitro models of cancer stem cells for in vivo xenograft models.  hiPSC differentiation into a desired tissue allows studying physiologic processes in human-relevantcell systems. By introducing disease-specific mutations, these cells allow studying genetic origins of diseases in a tissue-specific manner.

overall_design: Bisulphite converted DNA from the samples were hybridised to the Illumina Infinium MethylationEPIC Kit array

first: Narges

last: Mehrjardi

first: Daniel

last: Picard


title: A Micro-evolutionary Change in Target Binding Sites as a Key Determinant of Ultrabithorax Function in Drosophila [ChIP-seq]

summary: We profiled the genome wide binding of the Ubx protein in Drosophila halteres and identified its direct targets. Analysis of genome wide binding of Ubx helped us identify the role of high affinity motifs in target selection as well as Ubx mediated regulation of target genes in Drosophila halteres.

overall_design: We carried out Chromatin immunoprecipitation for the Ubx protein in wing and haltere imaginal discs in Drosophila L3 larvae using a polyclonal antibody raised against the N-terminal region of Drosophila Ubx. Sequencing was carried out on Illumina Hiseq 2500 platform. MACS2 software was used to identify Ubx peaks. All experiments were carried out on three independnt biological replicates.

first: L

middle: S


title: Epigenome analysis of hiPSC-based tumour models I

first: Constanze

last: Uhlmann


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

overall_design: Refer to individual Series


title: RNA sequencing for the TNF- or vehicle-treated mouse intestinal organoids

status: Public on Jul 03 2023

city: JiNan

first: Shiyang

last: Li

address: Wenhua West Road

institute: Shandong University

summary: RNA sequencing was performed for the TNF- or vehicle-treated organoids derived from the large intestine of healthy male C57BL/6J mice (n = 3 per group).

overall_design: The  large intestine of C57BL/6J mice were isolated to intestinal crypts. Isolated crypts were incubated alone or with  TNFα  in combination for 24 hours,the organoids were harvested by centrifugation and lysed for RNA extraction.

first: Mengqi

last: Zheng

first: Yunjiao

last: Zhai

first: Yanbo

last: Yu


title: RNA-Seq Transcriptomic Analysis of Human Trabecular Meshwork Explants Exposed to TGF-β2: A Novel Approach Beyond Traditional Cell Culture Models

city: Paris

first: Frederic

last: Blond

address: 17 rue Moreau

institute: Institut de la Vision

summary: Glaucoma is a progressive optic neuropathy that can lead to irreversible blindness. Its main risk factor is elevated intraocular pressure (IOP). The trabecular meshwork (TM) acts as a filter between the anterior chamber of the eye and the aqueous humor collecting ducts, and dysfunction of this meshwork is responsible for the increased IOP in primary open-angle glaucoma (POAG). Considering that the culture conditions of human TM cells (HTMC) influence gene expression, we used human TM explants (HTMEx), which most closely mimic physiological conditions, to study the transcriptome of HTMC. The transforming growth factor-beta 2 (TGF-β2) signaling pathway has been implicated in the pathophysiology of POAG. To better characterize the role of TGF-β2 in this pathophysiology, we used bulk RNA sequencing and immunohistological analyses to establish gene signatures of TGF-β2-exposed HTMEx and correlate them with morphological alterations.  We identified differentially upregulated genes primarily involved in ECM regulation, as well as profibrotic TGF-β signaling pathways, confirmed using confocal microscopy to highlight changes in trabecular architecture, TGFβ2-induced F-actin rearrangements, and extracellular matrix (ECM) deposition. Enrichment analysis also revealed modulations of gene expression related to cytoskeletal organization, as well as activation of the bone morphogenic protein (BMP) and Wnt signaling pathways in response to TGF-β2.

overall_design: To gain a better understanding of the role of TGF-β2 in the molecular pathology of glaucoma, we used bulk RNA-Seq to analyze changes in the transcriptome of HTMEx exposed to TGF-β2.

first: Juliette

last: Buffault

first: Élodie

last: Reboussin

first: Karima

last: Kessal

first: Murat

last: Akkurt Arslan

first: Frédéric

first: Xavier

last: Guillonneau

first: Stéphane

last: Melik Parsadaniantz

first: Annabelle

last: Reaux Le Goazigo

first: Antoine

last: Labbé

first: Françoise

last: Brignole-Baudouin

first: Christophe

last: Baubouin


title: Origins of proprioceptor feature selectivity and topographic maps in the Drosophila leg

city: Houston

first: Hongjie

state: TX

address: One Baylor Plaza

department: Huffington Center on Aging

institute: Baylor College of Medicine

summary: Our ability to sense and move our bodies relies on proprioceptors, sensory neurons that detect mechanical forces within the body. Proprioceptors are diverse: different subtypes detect different features of joint kinematics, such as position, directional movement, and vibration. However, because they are located within complex and dynamic peripheral tissues, the underlying mechanisms of proprioceptor feature selectivity remain poorly understood. Here, we investigate molecular and biomechanical contributions to proprioceptor diversity in the Drosophila leg. Using single-nucleus RNA sequencing, we found that different proprioceptor subtypes express similar complements of mechanosensory and other ion channels. However, anatomical reconstruction of the proprioceptive organ and connected tendons revealed major biomechanical differences between proprioceptor subtypes. We constructed a computational model of the proprioceptors and tendons, which identified a putative biomechanical mechanism for joint angle selectivity. The model also predicted the existence of a goniotopic map of joint angle among position-tuned proprioceptors, which we confirmed using calcium imaging. Our findings suggest that biomechanical specialization is a key determinant of proprioceptor feature selectivity in Drosophila. More broadly, our discovery of proprioceptive maps in the fly leg reveals common organizational principles between proprioception and other topographically organized sensory systems.

overall_design: Flies are raised on standard cornmeal and molasses medium kept at 25 C in a 14:10 hour light:dark cycle.

first: Tzu-Chiao

last: Lu

first: John

middle: C

last: Tuthill

first: Akira

last: Mamiya


title: CBL and CBL-B Restrain Tfh Cell Responses and Systemic Lupus Erythematosus by Facilitating BCL-6 Degradation via the Chaperone-Mediated Autophagy

city: Montreal

first: Hua

last: Gu

state: qc

address: 110 Pine avenue west

country: Canada

institute: The Clinic research Institute of Montreal

summary: Hyper Tfh cell responses have been linked to some SLE patients; however, molecular traits leading to the abnormal Tfh cell homeostasis and SLE remains elusive. Li et al. show here that a cohort of active SLE patients simultaneously downregulate CBL and CBL-B (CBLs) in CD4+ T cells and have increased blood circulating Tfh (cTfh) cells which upregulate ICOS and BCL6. Ablation of CBLs in mouse T cells also leads to hyper Tfh cell responses and manifestation of SLE. They further show that under the normal circumstance BCL6 is degraded via chaperone-mediated autophagy (CMA), and this process is oppositely regulated by ICOS-AKT signaling and ICOS ubiquitination mediated by CBLs. Since CBLs also restrains human Tfh cell responses by the same regulatory mode, downregulation of CBLs in human T cells likely to be causative to development of SLE in humans.

overall_design: To investigate the influence of the ICOS-CBLs signalling axis on the Tfh cell developmental program


title: Transcriptional circuits that regulate early T cell precursor acute leukemia [HiChIP]

city: New York

first: Javier

last: Rodriguez Hernaez

state: New York

address: East 30th Street. 8th Floor

institute: NYU Langone Health

summary: The discovery of early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) was based on expression of stem cell genes that are characteristic of mouse ETP cells, the most primitive multipotent cells in the thymus. Using complementary mouse and human genetic models and genome-wide expression and chromatin profiling integrated with 3D chromatin mapping, we show that the PIAS-like coactivator ZMIZ1 promotes immature T-ALL proliferation by recruiting the transcription factor MYB in feedforward circuits to cooperatively induce MYCN, MEF2C, and BCL2, which were recently associated with the high-risk bone marrow progenitor (BMP-like) subset.

overall_design: Prototypical cell lines of early T cell precursor leukemia (ETP-ALL) were collected and analyzed for 3D chromatin structure.

first: Francesco

last: Boccalatte

first: Bettina

last: Nadorp

last: Rodriguez-Hernaez

first: Giovanni

last: Gambi

first: Ioannis

last: Aifantis

first: Aristotelis

last: Tsirigos


title: Gene expression data from human neural stem cells (hNSCs) treated with 10 uM TCQA for 24 hours

city: Tsukuba

first: Yu Jia

last: Chen

state: Ibaraki

address: 1 Chome-1-1 Tennodai

country: Japan

institute: University of Tsukuba

summary:
TCQA promoted differentiation of hNSCs at least toward the neuronal lineage and suggests the possibility of using TCQA to promote neurogenesis.
When differentiation is induced by growth factor withdrawal, decreased expression of stemness gene and increased expression of NSC fate-promoting genes can be observed. Therefore, we evaluated the effect of TCQA on global gene expression in hNSCs during differentiation at 24h to elucidate the neurogenesis-promoting effects of TCQA.

overall_design: The total RNA was extracted from the cells using ISOGEN kit (Nippon Gene Co. Ltd., Toyama, Japan) following manufacturer’s instructions. Total RNA was quantified and assessed for quality with a NanoDrop 2000 spectrophotometer (Thermo Scientific, Wilmington, DE, USA). Double-stranded cDNA was synthesized from 100 ng of total RNA with the GeneAtlas 3’ IVT Express Kit (Affymetrix Inc., Santa Clara, CA, USA). Biotin-labeled amplified RNA (aRNA) was synthesized by in vitro transcription using the GeneChip 3’ IVT Express Kit (Affymetrix Inc., Santa Clara, CA, USA). A total of 9.4 mg of purified aRNA was fragmented using the GeneAtlas 3’ IVT Express Kit and was hybridized for 16 h at 45°C using GeneChip MG-430 PM microarray (Affymetrix Inc., Santa Clara, CA, USA). The chip was washed and stained in the Gene Atlas Fluidics Station 400 (Affymetrix Inc., Santa Clara, CA, USA) and then the resulting image was scanned using the GeneAtlas Imaging Station (Affymetrix Inc., Santa Clara, CA, USA). Data analysis was performed using the Partek Express software (Partek Inc., St. Louis, MO, USA) provided by Affymetrix as part of their GeneAtlas system. Compared with the non-treated cells, fold change in expression in the TCQA-treated group was calculated and converted to log 2 data.

first: Ashley


title: CTLA-4 pathway is instrumental in Giant Cell Arteritis

first: Paul

last: Régnier

address: 83 boulevard de l'hôpital

institute: AP-HP

summary:
BACKGROUND: Giant Cell Arteritis (GCA) causes severe inflammation of the aorta and its branches and is characterized by intense effector T cells infiltration. The roles that immune checkpoints play in pathogenesis of GCA are still unclear.Our aim was to study the immune checkpoints interplay in GCA. METHODS: First, we used VigiBase, the WHO international pharmacovigilance database, to evaluate the relationship between GCA occurrence and immune checkpoint inhibitors (ICI) treatments. We then further dissected the role of ICI in the pathogenesis of GCA, using immunohistochemistry, immunofluorescence, transcriptomics and flow cytometry on peripheral blood mononuclear cells (PBMCs) and aortic tissues of GCA patients and appropriated controls.
RESULTS: Using VigiBase, we identified GCA as a significant immune related adverse event associated with anti-CTLA-4 (Cytotoxic T-lymphocyte-associated-protein-4) but not anti-PD-1/PD-L1 treatment. We further dissected a critical role for CTLA-4 pathway in GCA by identification of the dysregulation of CTLA-4-derived gene pathways and proteins in CD4+ T cells (and specifically Tregs) present in blood and aorta of GCA patients versus controls. While Tregs were less abundant and activated/suppressive in blood and aorta of GCA versus controls, they still specifically upregulated CTLA-4. Activated and proliferating CTLA-4+ Ki-67+ Tregs from GCA were more sensitive to anti-CTLA-4 (Ipilimumab)-mediated in vitro depletion versus controls. CONCLUSIONS: We highlighted the instrumental role of CTLA-4 immune checkpoint in GCA which provides a strong rationale for targeting this pathway.

overall_design: We performed Illumina HumanHT-12 V4 beadarray assay on MACS-sorted CD4+ T cells extracted from PBMCs obtained from whole blood of 15 healthy donors (HD) and 19 patients with active Giant Cell Arteritis (aGCA).

first: Alexandre

last: Le Joncour

first: Anna

last: Maciejewski-Duval

first: Guillaume

last: Darrasse-Jèze

first: Charles

last: Dolladille

first: Wouter

last: Meijers

first: Lisa

last: Bastarache

first: Pierre

last: Fouret

first: Patrick

last: Bruneval

first: Floriane

last: Arbaretaz

first: Célia

last: Sayetta

first: Ana

last: Márquez

first: Michelle

last: Rosenzwajg

first: David

last: Klatzmann

first: Patrice

last: Cacoub

first: Javid

middle: J

last: Moslehi

first: Joe-Elie

last: Salem

last: Saadoun


title: Transcription factors interact with RNA to regulate genes (CLIP-Seq)

first: Richard

middle: A

last: Young

state: MA

address: 9 Cambridge Center

institute: Whitehead Institute for Biomedical Research

summary: Transcription factors (TFs) orchestrate the gene expression programs that define each cell’s identity. The canonical TF accomplishes this with two domains, one that binds specific DNA sequences and the other that binds protein coactivators or corepressors. We find that at least half of TFs also bind RNA, doing so through a previously unrecognized domain with sequence and functional features analogous to the arginine-rich motif of the HIV transcriptional activator Tat. RNA binding contributes to TF function by promoting the dynamic association between DNA, RNA and TF on chromatin. TF-RNA interactions are a conserved feature essential for vertebrate development and disrupted in disease. We propose that the ability to bind DNA, RNA and protein is a general property of many TFs and is fundamental to their gene regulatory function.

overall_design: Modified seCLIP for K562 cells stably expressing human GATA2.

first: Ozgur

last: Oksuz

first: Jonathan

middle: E

last: Henninger

first: Lauren

middle: N

last: Reich

first: Roberto

last: Bonasio


title: Oxygen-sensing through ERFVII action and modulation in Arabidopsis thaliana

city: Nottingham

first: Michael

last: Holdsworth

address: University of Nottingham, University Park

institute: University of Nottingham

summary: Oxygen is a key signalling component of plant biology, and whilst an oxygen-sensing mechanism was previously described in Arabidopsis thaliana, key features of the associated PCO N-degron pathway and Group VII ETHYLENE RESPONSE FACTOR (ERFVII) transcription factor substrates remain unknown. We demonstrate that ERFVIIs show non-autonomous activation of root hypoxia tolerance, and are essential for root development and survival under oxygen limiting conditions in the soil. We determine the combined effects of ERFVIIs in controlling genome expression and define genetic and environmental components required for proteasome-dependent oxygen-regulated stability of ERFVIIs through the PCO N-degron pathway. Using a plant extract, unexpected amino-terminal cysteine sulphonic acid oxidation level of ERFVIIs was observed, suggesting a requirement for additional enzymatic activity within the pathway. Our results provide a holistic understanding of the properties, functions and readouts of this oxygen-sensing mechanism defined through its role in modulating ERFVII stability.

overall_design: 7 days old seedlings of WT and mutant lines were harvested untreated

first: Gunjan

last: Sharma


title: Transcription factors interact with RNA to regulate genes (CUT&Tag)

overall_design: CUT&Tag for mESCs expressing WT or ARM-mutant SOX2 and KLF4


title: Hypertension state and overweight/obesity affect the transcriptome alternation in Human Visceral Adipose Tissue

city: Yantai

first: Lanlan

last: Liao

state: Shandong Province

address: No. 346, Guanhai Road, Laishan District, Yantai City, Shandong Province; No. 20, Yuhuangding East Road, Zhifu District, Yantai City

department: The Second Clinical Medical College, Department of Cardiovascular Medicine

institute: Binzhou Medical College, Yantai Yuhuangding Hospital

summary: In order to explore the effect of hypertension and overweight/obesity on human visceral adipose tissue transcriptome, we collected three visceral adipose tissue samples from normal weight individuals (non hypertension), overweight/obese individuals (non hypertension) and overweight/obese individuals with hypertension, and sequenced their transcriptome.

overall_design: We collected three visceral adipose tissue samples from normal weight individuals (non hypertension), overweight/obese individuals (non hypertension) and overweight/obese individuals with hypertension, and sequenced their transcriptome.

first: Jun

last: yang

first: Zhen

last: Shi

first: Lin

last: Zhong


title: A mucin-regulated adhesin determines the spatial organization and inflammatory character of a bacterial symbiont in the vertebrate gut

city: Eugene

first: Timothy

middle: Jarrod

last: Smith

state: Oregon

address: 1229 University of Oregon

institute: University of Oregon

summary: In a healthy gut, microbes are often aggregated with host mucus, yet the molecular basis for this organization and its impact on intestinal health are unclear. Mucus is a viscous physical barrier separating resident microbes from epithelia, but also provides glycan cues that regulate microbial behaviors. Here, we describe a mucin-sensing pathway in an Aeromonas symbiont of zebrafish, Aer01. In response to the mucin-associated glycan N-acetylglucosamine, a sensor kinase regulates expression of an aggregation-promoting adhesin we named MbpA. Upon MbpA disruption, Aer01 colonizes to normal levels, but is largely planktonic and more immunogenic. Increasing cell surface MbpA rescues these traits. MbpA-like adhesins are common in human-associated bacteria and expression of an Akkermansia muciniphila MbpA-like adhesin in MbpA-deficient Aer01 restores lumenal aggregation and reverses its pro-inflammatory character. Our work demonstrates how resident bacteria use mucin glycans to modulate behaviors congruent with host health.

overall_design:
The larval zebrafish symbiont, Aeromonas ZOR0001 (Aer01), forms denser aggregates in the mucin-rich gut lumen of its host or when exposed to the mucin-associated sugar N-acetylglucosamine (GlcNAc). To investigate the genetic basis of this response in culture we exposed Aer01 to 0.4% GlcNAc or 0.4% Glucose, a glycan that doesn’t promote Aer01 aggregation.
We similarly exposed two experimentally evolved Aer01 isolates that fail to aggregate when exposed to GlcNAc to this sugar to determine how Aer01 GlcNAc-mediated transcriptional responses are altered in these isolates.
RNA was harvested after 6 hours of GlcNAc or Glucose exposure and submitted to SeqCenter for RNA-seq analysis.

first: T

first: Karen

last: Guillemin


title: Transcriptional circuits that regulate early T cell precursor acute leukemia

first: Javier

last: Rodriguez Hernaez

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus


title: Transcriptional circuits that regulate early T cell precursor acute leukemia [Hi-C]

overall_design: Mouse bone marrow-derived hematopoietic stem and progenitor cells (Lin-Sca+Kit+) were collected and analyzed for 3D chromatin structure.

first: Francesco

last: Boccalatte

first: Bettina

last: Nadorp

last: Rodriguez-Hernaez

first: Giovanni

last: Gambi

first: Ioannis

last: Aifantis

first: Aristotelis

last: Tsirigos


title: Choroid plexus mis-splicing and altered cerebrospinal fluid composition in myotonic dystrophy type 1 [human]

city: Gainesville

first: Curtis

last: Nutter

state: FL

address: 2033 Mowry Road

department: Molecular Genetics and Microbiology

institute: University of Florida

summary: Myotonic dystrophy type 1 is a dominantly inherited multisystemic disease caused by CTG tandem repeat expansions in the DMPK 3' untranslated region. These expanded repeats are transcribed and produce toxic CUG RNAs that sequester and inhibit activities of the MBNL family of developmental RNA processing factors. Although myotonic dystrophy is classified as a muscular dystrophy, the brain is also severely affected by an unusual cohort of symptoms, including hypersomnia, executive dysfunction, as well as early onsets of tau/MAPT pathology and cerebral atrophy. To address the molecular and cellular events that lead to these pathological outcomes, we recently generated a mouse Dmpk CTG expansion knockin model and identified choroid plexus epithelial cells as particularly affected by the expression of toxic CUG expansion RNAs. To determine if toxic CUG RNAs perturb choroid plexus functions, alternative splicing analysis was performed on lateral and hindbrain choroid plexi from Dmpk CTG knockin mice. Choroid plexus transcriptome-wide changes were evaluated in Mbnl2 knockout mice, a developmental-onset model of myotonic dystrophy brain dysfunction. To determine if transcriptome changes also occurred in the human disease, we obtained post-mortem choroid plexus for RNA-seq from donors without neurologically unaffected (two females, three males; ages 50-70) and myotonic dystrophy type 1 donors (one female, three males; ages 50-70). To test that choroid plexus transcriptome alterations resulted in altered CSF composition, we obtained CSF via lumbar puncture from patients with myotonic dystrophy type 1 (five females, five males; ages 35-55) and non-myotonic dystrophy patients (three females, four males; ages 26-51) and Western blot and osmolarity analyses were used to test CSF alterations predicted by choroid plexus transcriptome analysis. We determined that CUG RNA induced toxicity was more robust in the lateral choroid plexus of Dmpk CTG knockin mice due to comparatively higher Dmpk and lower Mbnl RNA levels. Impaired transitions to adult splicing patterns during choroid plexus development were identified in Mbnl2 knockout mice, including mis-splicing previously found in Dmpk CTG knockin mice. Whole transcriptome analysis of myotonic dystrophy type 1 choroid plexus revealed disease-associated RNA expression and mis-splicing events. Based on these RNA changes, predicted alterations in ion homeostasis, secretory output, and CSF composition were confirmed by analysis of myotonic dystrophy type 1 CSF. Our results implicate choroid plexus spliceopathy and concomitant alterations in CSF homeostasis as an unappreciated contributor to myotonic dystrophy type 1 CNS pathogenesis.

overall_design: We hypothesized extensive transcriptomic alterations occur in myotonic dystrophy type 1 LVChP. To test this hypothesis, LVChP was analyzed from post-mortem myotonic dystrophy type 1 patients , neurologically unaffected patients, and disease control patients (Alzheimer’s disease). RNA-seq was performed and analyzed for alternative splicing and differential expression changes due to myotonic dystrophy type 1 pathomechanisms.

first: Benjamin

middle: M

last: Kidd

first: Helmut

last: Carter

first: Łukasz

last: Sznajder

first: Eric

middle: T

last: Wang

first: Laura

middle: P

last: Ranum

first: John

middle: W

last: Day

first: Jacinda

middle: B

last: Sampson

first: Stefan

last: Prokop

first: Maurice

last: Swanson


title: FGF19 induces the inflammatory phenotype of LX-2 cells

first: Tianli

last: Chen

state: Shandong

address: 107 West Wenhua Road

department: Department of General Surgery

institute: Qilu Hospital of Shandong University

summary: Liver metastasis is the main cause of death for human colorectal cancer (CRC), thus effective biomarkers and therapeutic target of colorectal cancer liver metastasis (CRLM) are urgently needed. Here, we report that FGF19 mediated the polarization of hepatic stellate cells to inflammatory CAFs by activating the autocrine effect of IL-1α via JAK2-STAT3 pathway. FGF19-induced iCAFs produced complement C5a and IL-1β to enhance neutrophil extracellular traps (NETs) formation in liver metastases, which in turn accelerated the liver colonization of CRC cells.

overall_design: LX-2 cells were stimulated with hFGF19(50 ng/ml or 100 ng/ml) for 24 hours and subjected to differential gene expression studies by RNA-seq.

first: Chen

last: Li


title: Preliminary insights into RNA in CSF of SMA patients after Nusinersen “loading dose”

city: Pavia

first: Maria

last: Garofalo

address: Via Mondino 2

institute: IRCCS Mondino Foundation

summary: Antisense oligonucleotide (ASO) nusinersen (Spinraza®) modulates the pre–mRNA splicing of the SMN2 gene, allowing rebalance of biologically active SMN. It is administered intrathecally via lumbar puncture after removing an equal amount of cerebrospinal fluid (CSF). Its effect was proven beneficial and approved since 2017 for SMA treatment. Since the direct effect of nusinersen on RNA metabolism, the aim of this project was to evaluate cell-free RNA (cfRNA) in CSF of SMA patients under ASOs treatment for biomarker discovery.

overall_design: By RNA-sequencing approach, RNA obtained from CSF of SMA type 2 and 3 patients was processed after 6 months of nusinersen treatment, at fifth intrathecal injection (T6) and compared to baseline (T0).

first: Silvia

last: Bonanno

first: Stefania

last: Marcuzzo

first: Cecilia

last: Pandini

first: Eveljn

last: Scarian

first: Susanna

last: Zucca

first: Stefano

last: Parravicini

first: Riccardo

last: Masson

first: Claudia

last: Dosi

last: Zanin

first: Orietta

last: Pansarasa

first: Cristina

last: Cereda

first: Angela

last: Berardinelli

first: Stella

last: Gagliardi


title: Transcriptome sequencing of equine sarcoids and skin samples

city: Balice

first: Ewelina

last: Semik-Gurgul

address: Krakowska 1

department: Department of Animal Molecular Biology

country: Poland

institute: National Research Institute of Animal Production

summary: The aim of this study was to identify changes in transcriptome of horse sarcoids - a locally invasive skin tumors of equids, which are considered to be the most common equine skin neoplasm. The global expression of genes was investigated in 12 tumour samples and in 12 of healthy skin samples.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for  12 equine sarcoids and 12 skin controls was performed using the Illumina NovaSeq platform.

first: Tomasz

last: Szmatoła

first: Klaudia

last: Pawlina-Tyszko

first: Artur

last: Gurgul


title: Choroid plexus mis-splicing and altered cerebrospinal fluid composition in myotonic dystrophy type 1 [mouse]

first: Curtis

last: Nutter

overall_design: We collected and performed RNA-seq on Choroid plexus tissue from different mouse developmental stages either wild type or knockout of splicing regulator Mbnl2. Transcriptomic analysis was performed to identify alternative splicing and gene expression changes during development and upon loss of Mbnl2

first: Benjamin

last: Kidd

first: Helmut

last: Carter

first: Nayha

last: Kumbkarni

first: Dana

last: Tuyn

first: Łukasz

last: Sznajder

first: Eric

last: Wang

first: Maurice

last: Swanson


title: Gene expression profile at single cell level of  four PBS injected mice, six tumor-bearing mice and four  tumor-bearing mice treated with anti-IL-1α.

city: Bellinzona

first: Luciano

last: Cascione

state: Ticino

address: Via Chiesa 5

department: Lymphoma & Genomics Research Program

country: Switzerland

institute: IOR

summary: We used single cell RNA sequencing (scRNA-seq) to analyze the diversity transcriptomic profiles micro-surgically dissected metastatic regions of the sentinel lymphonodes (3 different condition)

overall_design:
we micro-surgically dissected the metastatic regions of the sLNs and analyzed them by single-cell RNA sequencing
Treatment groups:
neg control: PBS
control: tumor-bearing mice
treatment: tumor-bearing mice treated with anti-IL-1α

first: Tommaso

last: Virgilio

first: Santiago

middle: F

last: Gonzalez


title: Choroid plexus mis-splicing and altered cerebrospinal fluid composition in myotonic dystrophy type 1

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

overall_design: Refer to individual Series


title: Reduced representation bisulfite sequencing of equine sarcoid andhorse skin samples

summary: DNA methylation is a key mechanism in transcription regulation, and aberrant methylation is a common and important mechanism in tumor initiation, maintenance, and progression. To find genes that are aberrantly regulated by altered methylation in horse sarcoids, we used reduced representation bisulfite sequencing (RRBS) accompanied by RNA sequencing (RNA-Seq) for methylome (whole genome DNA methylation sequencing) and transcriptome profiling, respectively. We found that the DNA methylation level was generally lower in lesion samples than in controls. In the analyzed samples, a total of 14,692 differentially methylated sites (DMSs) in the context of CpG (where cytosine and guanine are separated by a phosphate), and 11,712 differentially expressed genes (DEGs) were identified. The integration of the methylome and transcriptome data suggests that aberrant DNA methylation may be involved in the deregulation of expression of the 493 genes in equine sarcoid. Furthermore, enrichment analysis of the genes demonstrated the activation of multiple molecular pathways related to extracellular matrix (ECM), oxidative phosphorylation (OXPHOS), immune response, and disease processes that can be related to tumor progression. The results provide further insight into the epigenetic alterations in equine sarcoids and provide a valuable resource for follow-up studies to identify biomarkers for predicting susceptibility to this common condition in horses.

overall_design: RRBS sequencing of 12 equine tissues and 12 skin controls was performed using the Illumina NextSeq 500/550 platform.


title: Transcription factors interact with RNA to regulate genes

first: Richard

last: Young


title: Nanostring analysis of non-activated or activated CAR T cells

city: London

first: Matteo

last: Righi

state: --None--

address: The MediaWorks, 191 Wood Lane

institute: Autolus Therapeutics

summary: Assessing transcriptomic differences between activation and non-activation of CAR T cells expressing different Chimeric Cytokine Receptors

overall_design: mRNA extraction after 24h of antigen starvation or 24h of CAR activation

first: M

first: I

last: Gannon


title: Multi-omic analysis reveals dynamic changes of three-dimensional chromatin architecture during T cell differentiation (RNA-Seq)

city: Shanghai

first: Ge

last: Zhang

address: Yueyang Road 320

institute: Shanghai Institute of Nutrition and Health,CAS

summary:
Background: Activation of T cells results in widespread changes in transcriptional programs and multi-level remodeling of three-dimensional genome architecture. Although many efforts have been made in dissecting the epigenomic regulation during T cell activation and differentiation, it remains to be investigated in depth how alterations in the local and global chromatin structure coordinate gene expression in this process.
Results: We characterize dynamic changes at different levels of chromatin organization during Naive CD4+ T (Naive) differentiation into T helper 17 (Th17) and T helper 1 (Th1) cells using Hi-C, RNA-Seq and ATAC-Seq assays. As a result of T cell activation, extensive changes occur at the transcriptome, chromatin accessibility and higher-order structure levels. We observe decreased short-range chromatin interactions and increased extra-long-range chromatin interactions upon activation. At compartment level, although A/B compartments have no apparent global switch, the intensity of compartmentalization markedly alters in activated T cells. At TAD level, a fraction of TADs is rearranged with increase TAD number upon activation. In addition, we identify promoter-enhancer (P-E) loops, many of which are associated with T cell activation or cell-type specificity, including Rorc encoding RORγt (retinoic-acid-receptor-related orphan receptor gamma t) that facilitates Th17 differentiation and Hif1a (hypoxia-inducible factor 1α) that responds to intracellular oxygen levels in Th1.
Conclusion: T cell activation is conserved at multiple levels across T helper cells and species. From the 3D genome perspective, these results provide fresh insights into heterogeneity and plasticity of T helper cells during T cell activation based on chromatin reorganization.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for naïve CD4+ T cells and corresponding T helper cells (Th17 and th1).

first: Ying

last: Li

first: Gang

last: Wei


title: Multi-omic analysis reveals dynamic changes of three-dimensional chromatin architecture during T cell differentiation (ATAC-Seq)

overall_design: Comparative chromatin accessibility analysis of ATAC-Seq data for naïve CD4+ T cells and corresponding T helper cells (Th17 and th1).


title: Characterization of leukemia progression in the Cbfb-MYH11 knockin mice by single cell RNA sequencing

city: Bethesda

first: Kai

last: Yu

state: Maryland

address: 50 South Drive, Bldg 50, Room 5151

institute: NHGRI

summary: We used single cell RNA-sequencing to investigate the expression changes during the progression of leukemia in a conditional knock-in mouse model.

overall_design: Single cell RNA-seq with FACS-isolated c-Kit+ cells from the bone marrow of wild type, pre-leukemic, and leukemic mice.

first: Jamie

last: Diemer

first: Michael

last: Kelly


title: Multi-omic analysis reveals dynamic changes of three-dimensional chromatin architecture during T cell differentiation (Hi-C)

overall_design: Cells were isolated from mouse pooled lymph nodes and spleens by magnetic nanoparticle based on isolation kit for naive CD4+ T cells from Miltenyi Biotec.


title: Autism-linked UBE3A gain-of-function mutation causes interneuron and behavioral phenotypes when inherited maternally or paternally in mice

city: Boston

first: Jeremy

last: Simon

address: 450 Brookline Ave

department: Department of Data Science

institute: Dana-Farber Cancer Institute


title: Mutations in cdon and boc affect trunk neural crest cell migration and slow-twitch muscle development in zebrafish

city: Easton

first: Ezra

last: Lencer

state: PA

address: 746 High Street

department: Department of Biology

institute: Lafayette College

summary: Bulk RNA-seq of isolated slow-twtich muscle and neural crest cells from 24 hours post fertilization zebrafish.

overall_design: Bulk RNA-seq data from FAC sorted slow-twitch muscle and neural crest cells isolated from trunks of 24 hours post fertilization zebrafish embryos. Trunks of embryos were manually dissected and cells were disassociated using Accumax. Embryos were doubly transgenic for tg(sox10:mRFP) transgene that labels neural crest cells and tgPAC(prdm1a:eGFP) transgene that labels slow-twitch muscle and muscle pioneer cells. Neural crest cells and slow-twitch muscle cells were isolated by FACS on a MoFlow XDP100, prepared for stranded Illumina sequencing, and sequenced on a NovaSeq600 (PE 150bp). Gene expression summaries were produced using featurecounts (subread package) and DESeq2.


title: Autism-linked UBE3A gain-of-function mutation causes interneuron and behavioral phenotypes when inherited maternally or paternally in mice (scRNA-Seq)

summary: The E3 ubiquitin ligase Ube3a is biallelically expressed in mitotic cells, including neural progenitors and glial cells, raising the possibility that UBE3A gain-of-function mutations might cause neurodevelopmental disorders irrespective of parent-of-origin. To test this possibility, we engineered a mouse line that harbors an autism-linked UBE3A-T485A (T508A in mouse) gain-of-function mutation and evaluated phenotypes in animals that inherited the mutant allele paternally, maternally, or from both parents. We found that both paternally and maternally expressed UBE3A-T485A resulted in elevated UBE3A activity in neural progenitors and glial cells where Ube3a is biallelically expressed. Expression of UBE3A-T485A from the maternal allele, but not the paternal one, led to a persistent elevation of UBE3A activity in postmitotic neurons. Maternal, paternal, or biparental inheritance of the mutant allele promoted embryonic expansion of Zcchc12 lineage interneurons which mature into Sst and Calb2 expressing interneurons, and caused a spectrum of behavioral phenotypes that differed by parent-of-origin. Phenotypes were distinct from those observed in Angelman syndrome model mice that harbor a Ube3a maternal loss-of-function allele. Our study shows that the UBE3A-T485A gain-of-function mutation causes distinct neurodevelopmental phenotypes when inherited maternally or paternally. These findings have clinical implications for a growing number of disease-linked UBE3A gain-of-function mutations.

overall_design: Single-cell RNA-seq (drop-seq) of mouse cerebral cortex from Ube3a-WT, Ube3a-T485A homozygotes, assessed at two ages: E14.5 and P0

first: Lei

last: Xing

first: Mark

last: Zylka


title: Autism-linked UBE3A gain-of-function mutation causes interneuron and behavioral phenotypes when inherited maternally or paternally in mice (Bulk RNA-Seq)

overall_design: RNA-seq of mouse cerebral cortex from Ube3a-WT, Ube3a-T485A homozygotes, Ube3a-T485A maternal heterozygotes, and Ube3a-T485A paternal heterozygotes, assessed at four ages: E14.5, 1 month, 6 month, and 12 months old


title: Activation of FXR by bile acids in hepatic stellate cells plays a critical role in liver cirrhosis

city: NEW YORK

first: Robert

last: Schwabe

state: NY

address: 1130 ST NICHOLAS AVE - ROOM 916B

department: Medicine

institute: Columbia University

summary:
Cirrhosis is a late stage of fibrosis impairing liver function. Genetic animal models for cirrhosis are lacking, and molecular mechanisms remain unknown. We report the first murine genetic model recapitulating human cirrhosis induced by hepatocyte-specific elimination of MCRS1, a member of NSL and INO80 chromatin-modifier complexes. MCRS1 loss in hepatocytes modulates the expression of bile acid (BA) transporters, with a pronounced NTCP downregulation, concentrating BAs in liver sinusoids, thereby activating hepatic stellate cell (HSC) via FXR. Consistently, genetic FXR ablation in HSCs suppresses fibrotic marks in mice and in vitro cell culture. Mechanistically, deletion of a putative SANT domain from MCRS1 evicts HDAC1 from its H3 anchoring sites, increasing histone acetylation of BA transporter genes, modulating their expression and perturbing BA flow. Accordingly, human cirrhosis displays loss of nuclear MCRS1 and decreased NTCP expression. Thus, histone acetylation-mediated dysregulation of BA transporters, and consequently FXR activation by BAs in HSCs represent a central and universal signaling event in cirrhosis.
The data is from single-nuclei RNA-seq of whole-liver collected during autopsy of 4 individuals with COVID-19 and PMI < 4.5 hours

overall_design:
All liver specimens were collected (under IRB approved protocols, appropriate consent and ethical standards) during autopsy of individuals with COVID-19. The samples include three male and one female (age 70-83 years) and the post-mortem incision time for autopsy was less than 4.5 h. Liver samples were processed in a biosafety cabinet equipped for working with COVID-19 . The tissue was dissociated and nuclei were seperated using the steps detailed in the 'Methods'. After counting, nuclei were immediately processed for droplet-based singe nuclei RNA sequencing (snRNA-seq). snRNA-seq library prep details are in 'Methods'. Single-nuclei RNA libraries were quantified using Tapestation D1000 screening tapes (Agilent, Santa Clara, CA) and Qbit HS DNA quantification kit (Thermo Fisher Scientific). Libraries were pooled equimolarly and quantified using quantitative PCR. Libraries were sequenced on a NovaSeq 6000 with S4 flow cell (Illumina, San Diego, CA) using paired end, single index sequencing.

>>>Submitter states: Human raw sequencing data will be uploaded to controlled access database to meet institutional protocols.<<<

first: Ajay

last: Nair

first: Johannes

last: Melms

first: Amanda

last: Garrido

first: Nabil

last: Djouder

first: Benjamin

last: Izar


title: Combined CRISPR and proteomics screening reveal a cohesin-CTCF-bound allele contributing to increased expression of RUVBL1 and prostate cancer progression

city: TAMPA

first: Liang

last: Wang

address: 14059 Riveredge Drove

institute: Moffitt Cancer Center

sample_organism:
Homo sapiens
Expression vector lentiGuide-Puro


title: Melatonin decreases extremely high glucose induced mesothelial cell injury

city: Dalian

first: Feng

last: Zheng

state: Liaoning

address: West 9 Lvshun South Boulevard

institute: Second Hospital; Advanced Institute for Medical Sciences, Dalian Medical University.

summary: From initial RNAseq analysis, we found that a significant number of genes associated with inflammatory responses and related to mitochondrial structure and function were altered by high-glucose, while these changes were attenuated by melatonin treatment.

overall_design: Mesothelial cells were treated with normal or 236mM glucose in the presence or absence of 200mM melatonin and cells were collected after 6 and 12 hours.

first: Xuejuan

first: Hongxia

last: Ruan


title: Antiviral function of type I and type III interferons in the olfactory epithelium

city: Davis

first: Qizhi

last: Gong

state: CA

address: One Shields Avenue

department: Cell Biology and Human Anatomy

institute: University of California Davis, School of Medicine

summary:
Background: The olfactory epithelium (OE) is one of the few sites where environmental pathogens can gain direct access to the brain. Despite this vulnerable arrangement, little is known about the protective mechanisms in the OE to prevent viral infection and subsequent entry into the brain.
Methods: We systematically investigated acute responses in the olfactory mucosa (OM) upon exposure to vesicular stomatitis virus (VSV) by RNA-seq. VSVs were nasally inoculated into C57BL/6 mice. OM were dissected for gene expression analysis at different time points after viral inoculation. Interferon functions were determined by comparing viral gene expression in interferon (Ifn) receptor knockout (Ifnar1-/- and Ifnlr1-/-) with wildtype OM.
Results: Antiviral responses were observed as early as 24hrs post viral exposure in the OM. Amongst the rapidly upregulated transcripts observed were specific type I as well as type III Ifns and interferon stimulated genes. Genetic analyses demonstrated that both type I and type III IFN signaling are required for the suppression of viral replication in the OM. Nasal IFNb1 or IFNl2 administration effectively reduces viral load in the OM.
Conclusions: OE possesses innate ability to respond and suppress viral infection. Type I and type III IFNs actively participate in the OE’s antiviral functions. Nasal IFN application effectively blocks viral replication in the OE suggesting therapeutic potential against viral insult.

overall_design: Olfactory mucosa RNA samples obtained from different time points after nasal instillation of PBS or VSV were profiled by 3'tag RNA-seq


title: circRNA expression level in highly/low invasive HCC tissues

status: Public on Jul 02 2023

city: Hangzhou

first: Boqiang

last: Liu

address: 3rd Qingchun East Road, Han

institute: Zhejiang University

summary: Using the highly sensitive cricRNA array, we screened functional circRNAs in the human highly/low invasive HCC tissues, and the function of differentially expressed circRANs were analyzed by bioinformatics. The results revealed that circASH2 inhibits HCC metastasis by circASH2/YBX1/hnRNPs/TPM4 axis.

overall_design: In this study, 10 cases of HCC samples (including 5 highly invasive and 5 low invasive HCC tissues) were used to acquire the circRNA expression profiling.The definition criteria: Highly Invasive: a. tumor diameters were smaller than 3 cm; b. diagnosed as postsurgical metastasis or recurrence in three years, while Low Invasive: a. tumor diameters were larger than 3 cm; b. diagnosed as postsurgical metastasis or recurrence negative in three years. And, qRT-PCR was employed to confirm the results of circRNA microarrays.The functions of the differentially expressed circRNA were analyzed by bioinformatics methods.

last: Shi


title: Transient peripheral blood transcriptome response to ketamine treatment  in children with ADNP syndrome

city: New York

first: Ariela

last: Buxbaum Grice

address: 1 Gustave Levy Pl

department: Psychiatry

institute: Mount Sinai School of Medicine

summary: Activity-dependent neuroprotective protein (ADNP) syndrome is a rare neurodevelopmental disorder caused by mutations in the ADNP gene, resulting in intellectual disability, developmental delay and autism spectrum disorder (ASD). Ketamine treatment has emerged as a promising therapeutic option for children with ADNP syndrome, showing safety and significant behavioral improvements.  However, the underlying molecular perturbations caused by ketamine remain poorly described. We dissected the longitudinal effect of ketamine on the peripheral blood transcriptome of 10 individuals with ADNP syndrome. The blood transcriptome was profiled prior-to intravenous ketamine treatment (0.5mg/kg) and then again at five post-infusion timepoints: immediately post-infusion, day 1, week 1, week 2, and week 4. We show that a single low-dose infusion of ketamine triggers immediate and profound gene expression alterations, with specific enrichment of monocyte-related expression patterns. These alterations encompass diverse signaling pathways and co-expression networks, implicating up-regulation of immune and inflammatory-related processes and down-regulation of RNA processing mechanisms and metabolism. Notably, these changes exhibit a transient nature, returning to baseline levels 24 hours to 1 week after treatment. These findings advance our understanding of ketamine's molecular effects and provides a foundation for further research in elucidating its precise cellular and molecular targets. Moreover, the comprehensive assessment of ketamine-induced changes in ADNP syndrome contributes to the development of innovative therapeutic strategies for this challenging genetic disorder.

overall_design: We performed a comparative RNA-sequencing analysis of peripheral blood immune cells from 10 individuals with ADNP syndrome before and after intravenous ketamine (0.5mg/kg). Six timepoints were profiled, including one baseline measurement prior-to treatment and five post-infusion timepoints (immediately post-infusion, day 1, week 1, week 2, week 4). A multi-step analytical approach was used that specifically sought to provide a functional and mechanistic readout for ketamine response.

first: Buxbaum

middle: G

last: Ariela

first: Breen

last: Michael


title: Effect of knock-down of circASH2 on gene expression in HCC cells

summary: Metastasis, especially intrahepatical, is a major challenge for hepatocellular carcinoma (HCC) treatment. Cytoskeleton remodeling has been identified as a vital process mediating intrahepatic spreading. Previously we reported HCC tumor adhesion and invasion were modulated by circular RNA (circRNA), which has emerged as important regulators of various cellular processes and has been implicated in the cancer progression. Here we uncovered a novel nuclear circRNA, circASH2, which is preferentially lost in HCC tissues, and inhibits HCC metastasis by altering tumor cytoskeleton structure. Tropomyosin 4 (TPM4), a critical binding protein of actin, turned out to be the major target of circASH2 and was post-transcriptionally suppressed. Such regulation is based on mRNA/pre-mRNA splicing and degradation process. Furthermore, liquid-liquid phase separation (LLPS) of nuclear Y-box binding protein 1 (YBX1) enhanced by circASH2 augments TPM4 transcripts decay. Together, our data have revealed a novel tumor suppressive circRNA and more importantly, uncovered a fine regulation mechanism for HCC progression.

overall_design: To investigate the function of circASH2-silence in the regulation of HCC meatastasis, we established HCCLM3 and Huh7 cell lines with/without circASH2 knock-down. Then, we performed gene expression profiling analysis using data obtained from RNA-seq of 2 different HCC cells.


title: Extrachromosomal circular SUZ12 amplicon dictates retinoblastoma progression through reprogramming H3K27 methylation

first: Ludi

last: Yang

state: Shanghai

address: ZhiZaoju road，833，Shanghai, China

institute: Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine


title: Multi-omic analysis reveals dynamic changes of three-dimensional chromatin architecture during T cell differentiation

first: Ge

last: Zhang

summary:
This SuperSeries is composed of the SubSeries listed below.
Dynamic changes of three-dimensional chromatin architecture during T cell differentiation.


title: Extrachromosomal circular SUZ12 amplicon dictates retinoblastoma progression through reprogramming H3K27 methylation [RNA-seq]

summary: Extrachromosomal circular DNA (eccDNA) is double-stranded circular DNA that is derived from but independent of chromosomal DNA. Owing to its nonchromosomal inheritance, eccDNA facilitates the amplification of oncogenes and expedites the process of genome evolution in tumor. However, the role of eccDNA in RB remains enigmatic. Herein, we identified a set of SUZ12-containing eccDNAs in RB. Through multiomics analyses, we demonstrated that SUZ12 contributes to elevated levels of H3K27me3 modification and subsequently inhibits the transcription of KLF4 during the oncogenic progression of retinoblastoma. Conclusively, our study unveiled a novel SUZ12-containing eccDNA/H3K27me3 oncogenic mechanism where eccDNA dictates retinoblastoma progression through regulating transcription levels of linear DNA.

overall_design: Knockdown of SUZ12 in retinoblastoma cells affects its biological function

first: Peiwei

last: Chai

first: Xianqun

last: Fan


title: Transcriptome of EB differentiation at day 9th with or without PRDM16 or PR domain knock out [RNA-seq]

city: Ann Arbor

first: Fengbiao

last: Mao

state: Michigan

address: 1301 Catherine St

department: Department of Pathology

institute: University of Michigan

summary: This study describes the transcriptome profiling of EB differentiation at day 9th with or without PRDM16 or PR domain knock out

overall_design: RNA-Seq profiling on of EB differentiation at day 9th with or without PRDM16 or PR domain knock out. WT profiling compare with knock out can get specific gene expression profiling related to PRDM16 or PR domain during EB differentiation.

first: Yali

last: Dou


title: Genome-wide distribution of PRDM16, H3K4me1 and H3K4me2 in mouse ES cell line or EB day 6th [Cut&Run]

summary: The PRDM16, H3K4me1 and H3K4me2 levels are compared with or without the Prdm16 KO in mouse ES cells and EB day 6th

overall_design: Cut & Run profiling of PRDM16, H3K4me1 and H3K4me2 with or without the Prdm16 KO in mouse ES cells and EB day 6th


title: Effect of doxorubicin and SPEDOX-6 on human iPSC-derived cardiac spheroids comprised of cardiomyocytes, endothelial cells, and fibroblasts.

status: Public on Jul 01 2023

city: Los Angeles

first: Arun

last: Sharma

address: 8700 Beverly Blvd

department: Regenerative Medicine Institute

institute: Cedars-Sinai Medical Center

summary: The chemotherapeutic doxorubicin (DOX) detrimentally impacts the heart during cancer treatment. This necessitates development of non-cardiotoxic delivery systems that retain DOX anticancer efficacy. We utilized human induced pluripotent stem cell-derived multi-lineage cardiac spheroids (hiPSC-CSs)  to compare the anticancer efficacy and reduced cardiotoxicity of single protein encapsulated doxorubicin (SPEDOX-6), to standard unformulated (UF) DOX using RNA-sequencing. The cardiac spheroids are comprised of hiPSC-derived cardiomyocytes (hiPSC-CMs), hiPSC-derived endothelial cells (ECs), and hiPSC-derived cardiac fibroblasts (CFs) at an 8:1:1 ratio.

overall_design: Cardiac spheroid samples were treated with DMSO, unformulated doxorubicin at 5 micromolar, or SPEDOX-6 at 5 uM dox equivalent dose for 48 hours. RNA was then extracted using a QIAGEN RNA micro kit and submitted for bulk RNAsequencing.

first: Sharma

last: Arun

first: Cui

last: Xiaojiang


title: Effect of chemotherapy on the uterus of young adult cancer survivors

city: Provo

first: Timothy

last: Jenkins

state: UT

address: 4005 Life Sciences Building

department: Cell Biology and Physiology

institute: Brigham Young University

type: Methylation profiling by genome tiling array

summary: This pilot study aimed to accomplish 3 distinct but related goals. First, we described the structural phenotype of uterine/endometrial injury after alkylating chemotherapy sonographically and histologically. Second, we investigated the molecular impact of alkylating chemotherapy exposure on messenger RNA expression and epigenetic changes in endometrial biopsy (EMB) tissue homogenates. Third, we investigated the feasibility of performing ultrasonographic and EMB-based assessments in reproductive-age cancer survivors. Because of limited information available in this area of inquiry, this approach is exploratory and should prove to be hypothesis-generating. The main outcome measures of this study included endometrial thickness (EMT) and uterine volume on transvaginal  ultrasound. Endometrial histology, DNA methylation, and RNA-seq on EMB samples, and pain scale assessment before  and after EMB.

overall_design: The inclusion criteria were age of 18–45 years and consent for endometrial biopsy. The exclusion criteria were the absence of the uterus, completed pelvic radiation, uterine or cervical cancer, and metastatic cancer. Each participant underwent endometrial biopsy and pelvic ultrasound. All study visits were conducted in the late proliferative phase of the menstrual cycle.

first: Tim

first: Deepika

last: Garg

first: Matthew

last: Hodgman

first: Sydney

last: Reil

first: Lesley

last: Lomo

first: Kenneth

middle: I

last: Aston

first: Jonathon

last: Hill

first: Erica

last: Johnstone

first: Joseph

last: Letourneau


title: Transcriptomes of tissues of the razor clam Sinonovacula constricta

city: Ningbo

first: Zhaoshou

last: Ran

state: Zhejiang

address: Fenghua Road 818, Jiangbei Districta

department: Institute of Marine Science

institute: Ningbo University

summary: The razor clam Sinonovacula constricta (Lamarck 1818) is a famous marine bivalve species that widely distributed along the western Pacific coast with important economical and nutritional values. During the evolution, S. constricta has formed specific biological features to adapt to its living habit. To clarify the underlying molecular mechanism in forming the specific biological features, the tissues of siphon, gill, labial palp, foot, mantle, and intestine of S. constricta were subjected to RNA-sequencing. The results showed significant differences existed in gene expression among different tissues, which provided a molecular framework for understanding the differentiation of S. constricta tissues and their underlying specific biological functions.

overall_design: The tissues of siphon, gill, labial palp, foot, mantle, and intestine were collected from healthy adult S. constricta (65.23 mm × 22.78 mm, shell length × shell width). Each sample was triplicated, and derived form a mixture from three individuals. After RNA extraction, the samples were subjected to Pacific Biosciences RS sequencing instrument for RNA-sequencing (Novogene Bioinformatics Technology Co., Ltd, Beijing, China).

first: Fei

last: Kong

first: Jilin

last: Xu


title: Spatial Transcriptomic Profiling of Isolated Microregions in Tissue Section Utilizing Laser-induced Forward Transfer

city: nanjing

first: Kaiqiang

last: Ye

state: jiangsu

address: NO.2 SiPaiLou, Xuanwu district, Nanjing, Jiangsu Province, China

institute: Southeast University

summary: We use a laser-induced forward transfer (LIFT)-based  method coupled with a full-length mRNA-sequencing protocol (LIFT-seq) for profiling region-specific tissues.  LIFT-seq was applied to the cortex and hippocampus regions of the mouse brain for profiling gene expression.

overall_design: The ability of LIFT-seq to recover mRNA from isolated tissues was investigated on fresh frozen mouse brain sections by full-length mRNA-seq. To investigate if LIFT-seq could profile the gene expression of region-specific mROIs, we applied LIFT-seq to mouse brain cortex and hippocampus regions


title: Fascin actin-bundling protein 1 regulates non-small cell lung cancer progression by influencing transcription and splicing of tumorigenesis-related genes

city: Urumqi

first: Qingchao

last: Sun

state: Xinshi District

address: 137 Liyushan South Road

institute: The First Affiliated Hospital of Xinjiang Medical University

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

overall_design: Refer to individual Series


title: EB differentiation study

first: Fengbiao

last: Mao


title: Genome-wide binding of GFI1 in NB4 cells

first: Yun

last: Tan

address: Room 1109, Building 11, 197 Ruijin Er Rd

department: Shanghai Institute of Hematology

institute: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

summary: ChIP-seq analyses were conducted in NB4 cells with two antibodies against GFI1.

overall_design: Identification of GFI1 binding peaks in acute promyelocytic leukemia derived NB4 cells. Two antibodies against different moiety of GFI1 were used in ChIP experiments.

first: Kankan

last: Wang


title: Fascin actin-bundling protein 1 regulates non-small cell lung cancer progression by influencing transcription and splicing of tumorigenesis-related genes [IRIP-seq]

summary: Background. High mortality rates are prevalent among patients with non-small cell lung cancer (NSCLC), and effective therapeutic targets are key prognostic factors. Fascin actin-bundling protein 1 (FSCN1) promotes NSCLC; however, its role as an RNA-binding protein in NSCLC remains unexplored. Therefore, we aimed to explore FSCN1 expression and function in A549 cells.  Method. We screened for alternative-splicing events and differentially expressed genes (DEGs) after FSCN1 silence via RNA-sequencing (RNA-seq). FSCN1 immunoprecipitation followed by RNA-seq were used to identify target genes whose mRNA expression and pre-mRNA alternative-splicing levels might be influenced by FSCN1. Results. Silencing FSCN1 in A549 cells affected malignant phenotypes; it inhibited proliferation, migration, and invasion, and promoted apoptosis. RNA-seq analysis revealed 2851 DEGs and 3057 alternatively spliced genes. Gene ontology-based functional enrichment analysis showed that downregulated DEGs and alternatively splicing genes were enriched for the cell-cycle. FSCN1 promoted the alternative splicing of cell-cycle-related mRNAs involved in tumorigenesis (i.e., BCCIP, DLGAP5, PRC1, RECQL5, WTAP, and SGO1). Combined analysis of FSCN1 RNA-binding targets and RNA-seq data suggested that FSCN1 might affect ACTG1, KRT7, and PDE3A expression by affecting the pre-mRNA alternative-splicing levels of NME4, NCOR2, and EEF1D FSCN1 to long non-coding RNA transcripts (RNASNHG20, NEAT1, NSD2, and FTH1), which were highly abundant. Overall, extensive transcriptome analysis of gene alternative splicing and expression levels was performed in cells transfected with FSCN1 short-interfering RNA. Our data provide global insights into the regulatory mechanisms mediated by FSCN1 and its target genes in lung cancer.

overall_design: RIP-seq

first: Liwei

last: Zhang

first: Ruixue

last: Liu

first: Liang

last: Zong

first: Xiaoliang

last: Jing

first: Long

last: Ma

first: Jie

last: Li


title: Fascin actin-bundling protein 1 regulates non-small cell lung cancer progression by influencing transcription and splicing of tumorigenesis-related genes [RNA-seq]

overall_design: We screened for alternative-splicing events and differentially expressed genes (DEGs) after FSCN1 silence via RNA-sequencing (RNA-seq). FSCN1 immunoprecipitation followed by RNA-seq were used to identify target genes whose mRNA expression and pre-mRNA alternative-splicing levels might be influenced by FSCN1


title: Effect of germ-free status on transcriptional profiles in the nucleus accumbens and transcriptomic response to chronic morphine

city: Winston-Salem

first: Jonathon

last: Sens

state: NC

address: 115 S Chestnut St

department: Physiology/Pharmacology

institute: Wake Forest Baptist Health

summary: Opioid use disorder is a public health crisis that leads to tremendous suffering for patients as well as substantial social and economic cost for society. There are currently available treatments for patients with opioid use disorder, but they remain intolerable or ineffective for many. The need to develop new avenues for therapeutics development in this space is great. There is a tremendous amount of work that has been done in models of substance use disorders, including opioid use disorder, demonstrating that prolonged exposure to drugs of abuse leads to marked dysregulation of the transcriptional and epigenetic landscape of important limbic substructures. It is widely believed that these changes in the regulation of gene expression in response to drugs may be a key driving factor in the perpetuation of drug taking and seeking behaviors. Thus, development of interventions that could shape transcriptional regulation in response to drugs of abuse would be of high value. Over the past decade there has been a surge in research demonstrating that the resident bacteria of the gastrointestinal tract, collectively the gut microbiome, can have tremendous influence on neurobiological and behavioral plasticity. Previous work from our group and others has demonstrated that alterations in the gut microbiome can alter behavioral responses to opioids in multiple different paradigms. Additionally, we have previously reported that depletion of the gut microbiome with antibiotics markedly shifts the transcriptome of the nucleus accumbens following prolonged morphine exposure. In this manuscript we present a comprehensive analysis of the effects of the gut microbiome on transcriptional regulation of the nucleus accumbens following morphine by utilizing germ-free, antibiotic treated, and control mice. This allows for detailed understanding of the role of the microbiome in regulating baseline transcriptomic control, as well as response to morphine. We find that germ-free status leads to a marked gene dysregulation in a manner distinct to adult mice treated with antibiotics, and that altered gene pathways are highly related to cellular metabolic processes. These data provide additional insight into the role of the gut microbiome in modulating brain function and lay a foundation for further study in this area.

overall_design: NOT PROVIDED; REQUESTED

first: Rebecca

last: Hofford

first: Drew

middle: D

last: Kiraly


title: Biallelic variants in CSPG4 cause a novel neurodevelopmental disorder with intellectual disability, global developmental delay and facial anomalies

city: Doha

first: Sahar

middle: I.

last: Daas

state: Other

address: Sidra Medicine

country: Qatar

institute: Sidra Medicine

summary: We aimed to define a novel autosomal recessive neurodevelopmental disorder, characterize its clinical features, and identify the underlying genetic cause for this condition. Clinical and genetic data from affected individuals with neurological disorders were matched across families from five global sites. Here, we report five recessive CSPG4 (NM_001897) missense variants [three homozygous: c.A1370G (p.Asp457Gly), c.2627G>A (p.Arg876His) and c.3247C>A (p.Gln1083Lys), and two compound heterozygote: c.A1370G and c.5156A>G (p.Asp457Gly and p.Gln1719Arg) and c.658A>G and c.1220_1221delinsTG (p.(Thr220Ala and p.Pro407Leu)] by next-generation sequencing of five unrelated families with seven affected subjects. All subjects share a novel neurodevelopmental syndrome characterized by severe intellectual disability, global developmental delay, delayed ability to walk, speech and language delay, distinctive facial features, along with varying degrees of neurological impairment, including hypotonia, cerebellar hypoplasia, and/or seizures. All CSPG4 variants were predicted to be damaging using in silico tools, and three-dimensional molecular modeling suggested significant alterations in protein stability, compromising inter- and intra-molecular interactions. The impact on neurological and craniofacial development was analyzed in CRISPR/Cas9-mediated zebrafish models. CSPG4 variants affected notochord development, neuronal function, and cerebellar structure along with a disorganized head scaffold with anomalous skeletal and cartilage components. Two individuals metabolomics and crispant transcriptomics revealed significant perturbation of metabolites, extracellular matrix (ECM) regulating pathways, and genes previously described to cause mental retardation, dwarfism, and facial anomalies in humans. Our study links novel, rare, damaging variants of the ECM gene CSPG4 to a novel recessive Mendelian neurodevelopmental disorder in humans and supports the role of CSPG4 in early development.

overall_design: Zebrafish CSPG4 model RNA sequencing.  We used RNA sequencing of dissected heads from n=20 animals of each group, in 3 independent replicates.

last: Da'as

first: Ramzi

last: Temanni

first: Khalid

last: Fakhro


title: A targetable TAZ-TEAD2 pathway in HCC

first: Robert

last: Schwabe

summary: To investigate TAZ target genes in HCC development

overall_design: HTVI of EF1a-TAZS89A +CCl4 x 30 times (three times a week for 10 weeks)

first: Yoshinobu

last: Saito

first: Silvia

last: Affo


title: The elucidation of the anti-inflammatory mechanism of EMO in rheumatoid arthritis through an integrative approach combining bioinformatics and experimental verification

city: Hong Kong

first: chunhao

last: cao

address: Hong Kong

department: School of Chinese Medicine

country: Hong Kong

institute: Hong Kong Baptist University

summary: Emodin (EMO), a natural derivative of the anthraquinone family mainly extracted from rhubarb (Rheum palmatum), has previously been demonstrated to possess superior anti-inflammatory properties from a single target or pathway. In order to explore the underlying mechanism of action of EMO against rheumatoid arthritis (RA), a network pharmacology approach was employed.

overall_design:
We then designed three samples as the intervention group (D) and three as the control group (T).
Comparative gene expression profiling analysis of RNA-seq data for intervention group and  control group

first: Chunhao

last: Cao

first: Xiaofeng

last: Rong


title: Multi-omics approach revealed Pro-osteogenic properties of Barrier to antointegration factor 1 (BANF1)

city: Odense

first: Alexander

last: Rauch

address: Campusvej 55

department: Department of Clinical Research

country: Denmark

institute: University of Southern Denmark and Odense University Hospital

summary: Growth, remodeling, adaptation and repair of bone is critically dependent on the ability of tissue resident progenitors to differentiate into and thereby renew parenchymal cells of the osteoblast, chondrocyte, and adipocyte lineage. We recently reported that the activation of osteoblast-selective genes, such as alkaline phosphatase (ALPL), occurs through activation of pre-established enhancers, i.e., regulatory regions bound by transcriptional regulators prior to osteogenic induction. Using mass spectrometry-based quantitative proteomics, we identified 324 proteins with lineage-specific association to putative ALPL enhancer sequences during early osteoblast and adipocyte differentiation. Barrier to autointegration protein 1 (BANF1), known to be involved in chromatin compression and mutated in the Nestor-Guillermo progeria syndrome, was identified as a factor binding ALPL enhancers in an osteogenesis-selective manner. Using ChIP-seq analysis, we show here that BANF1associates with both structural and regulatory elements of the chromatin landscape in stromal cells and that BANF1 bound regulatory elements and nearby genes show increased activity upon osteogenic differentiation. Modulating BANF1 protein levels, first, alters expression of genes with nearby BANF1 binding, and second, strongly correlates with WNT signaling, osteogenic differentiation and bone forming capacity of the cells. Finally, genetic data reveal that the BANF1 locus harbors human sequence variations that correlate changes in bone mineral density and BANF1 expression while expression data from human bone related biopsies link decreased BANF1 expression with aging and osteoporosis. In conclusion, we identified BANF1 as a strong pro-osteogenic factor that is necessary for the maintenance of a cellular and molecular signature of osteoblast activity and bone formation in vivo.

overall_design: BANF1 ChIP-seq experiments were carried out in human bone marrow derived and TERT immortalized marrow stromal cells (hBM-MSC-TERT-4 cells) at the undifferentiated state and after 1 day of osteogenic and adipogenic induction

first: Michele

last: Puglia

first: Vyacheslav

last: Akimov

first: Inigo

last: Barrio-Hernandez

first: Nicholas

last: Ditzel

first: Thomas

middle: L

last: Andersen

first: Moustapha

last: Kassem

first: Susanne

last: Mandrup

first: Blagoy

last: Blagoev


title: Transcriptome analyses by RNA-seq with NELFE knockdown and EPZ-5676 or HMBA treated HCT116 cells

city: Seoul

first: Junyoung

last: Park

address: 84, Heukseok-ro

department: Department of Life Science

country: South Korea

institute: Chung-Ang University

summary: These analyses aim to investigate transcriptomic changes induced by NELFE knockdown or DOT1L inhibitor (EPZ-5676, 2 uM, 72 h) or p-TEFb activator (HMBA, 10 mM, 24 h) treatment in HCT116 cells

overall_design: We performed gene expression profiling using data obtained from RNA-seq with each condition.

first: Jooyoung

last: Kang

first: Sangbeom

last: Seo


title: Extrachromosomal circular SUZ12 amplicon dictates retinoblastoma progression through reprogramming H3K27 methylation [eccDNA-seq]

city: Shanghai

first: Ludi

last: Yang

summary: Extrachromosomal circular DNA (eccDNA) is double-stranded circular DNA that is derived from but independent of chromosomal DNA. Owing to its nonchromosomal inheritance, eccDNA facilitates the amplification of oncogenes and expedites the process of genome evolution in tumor. However, the role of eccDNA in RB remains enigmatic. We combined Circle-Seq and RNA-Seq to identified crucial extrachromosomal circular oncogene amplicons. Herein, we revealed that extrachromosomal circular SUZ12 amplicon regulates H3K27me3 modification during the oncogenic progression of retinoblastoma. Conclusively, our study initially delineated an integrated picture of the eccDNA landscape in retinoblastoma and unveiled a novel SUZ12-containing eccDNA/H3K27me3 oncogenic mechanism where eccDNA dictates retinoblastoma progression through regulating transcription levels of linear DNA.

overall_design: To identified crucial extrachromosomal circular oncogene amplicons in retinoblastoma

first: Peiwei

last: Chai

first: Xianqun

last: Fan


title: Genome-wide analysis of distribution of RNA Pol II ChIP-seq in NKAP depletion cells

first: Xing

last: Zhang

address: Insititute of Genetics, Zhejiang University, 866 Yuhangtang Rd

department: Institute of Genetics

summary: We performed ChIP-Seq analysis with an antibody against RNA polymerase II (Pol II). We found that the distribution of Pol II signals was decreased at the transcription start sites (TSSs) and transcription end sites (TESs) upon depletion of NKAP.

overall_design: Chromatin Immunoprecipitation DNA-Sequencing (ChIP-seq) to analyze RNA polymerase II in U2OS cells that were transfected with two different types of small interfering RNAs (siRNAs), namely NC and NKAP_KD.


title: H3K27me3 ChIP-sequencing of control and α-KG treated neonatal primary cardiomyocytes

city: Chongqing

first: Yu

last: Shi

state: Chongqing

address: 10 Changjiang Branch Road

department: Cardiology

institute: Military Medical University

summary: purpose:To compare the enrichment of H3K27me3 on genes after treatment of control and α-KG. Method: Primary cardiomyocytes were treated with control (PBS) and α-KG for 24 h and precipitated with H3K27me3 antibody, then, the precipitated sequences were analysed by next generation RNA-seq. Results: There are significant differences between control and α-KG group. Conclusion:H3K27me3 ChIP-seq was used for analysing the enrichment of H3K27me3 on genes.

overall_design: PBS treated primary cardiomyocytes and α-KG treated primary cardiomyocytes

first: Miao

last: Tian

first: Luxun

last: Tang


title: Microglia regulate basal cerebral blood flow and neurovascular coupling through ectonucleotidase CD39

city: Charlottesville

first: Anwaruddin

last: Mohammad

state: VA

address: Pinn Hall

department: Bioinformatics Core

institute: University of Virginia

summary: Microglia tightly interact with brain capillaries and regulate blood brain barrel permeability in pathological conditions. However, it is still unknown whether and how microglia regulate CBF in homeostatic condition. Here we show microglia directly regulate cerebral blood flow (CBF) and neurovascular coupling. Conditional knockout of microglial CD39 resulted in CBF hyper perfusion, reduced ATP induced CBF increase, impaired neurovascular coupling by whisker stimulation and reduced whisker stimulation induced adenosine increase in barrel cortex. Out data suggest that microglia is an important player for CBF regulation.

overall_design: Two groups are included. Four mice were included in each group. One group is PLX3397 food treated mice group. In this group microglia were depleted by CSF1r inhibitor. The other group is control group, in which mice were treated with control food.

first: Zhongxiao

last: Fu

first: Malli

last: Ganesana

first: Philip

last: Hwang

first: Eyo

last: Ukpong

first: Pankaj

last: Jumar

first: Jill

last: Venton

first: Anne

last: Schaefer

first: Chia-Yi

last: Kuan


title: Development of gene expression signatures for Buyang Huanwu decoction in treating intracerebral hemorrhage

city: Changsha

first: Teng

last: Li

address: Xiangya Road

institute: central south university xiangya hospital

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

summary: To identify the potential lncRNA and mRNA asscociated with Buyang Huanwu decoction (BYHWD) in treating intracerebral hemorrhage (ICH), we have employed lncRNA microarray expression profiling. 1596 and 1114 mRNAs were identified in the ICH vs sham group and the BYHWD vs ICH group, respectively. Specifically, 180 DEmRNAs were intersected among the three groups. 2287 and 2245 lncRNAs were identified in the ICH vs sham group and the BYHWD vs ICH group, respectively. Specifically, 342 DElncRNAs were intersected among the three groups. Expression of four mRNA (Spata2, Nkiras, Mef2c, Sh2b3) and lncRNA (Gm16045, Gm14005, Gm41118, 493304012Rik) from this signature was quantified by qPCR.

overall_design: Brain samples were detected at 14 d after ICH.

first: Tao


title: Single-cell RNA profiling of mononuclear phagocyte in colorectal cancer

city: Wuhan

first: Fu

last: Haoyu

state: Hubei

address: 1277 Jiefang Avenue

department: Department of Gastrointestinal Surgery

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

summary: During mononuclear phagocyte system evolution, monocytes differentiate into pro-tumorigenic TAMs. We used single cell RNA sequencing (scRNA-seq) to analyze the characteristics of mononuclear phagocyte in colorectal cancer

overall_design: Mononuclear phagocyte of 3 CRC patients were sorted by MACS and analyzed using scRNAseq.

first: Ji

last: Tiantian

first: Wang

last: Guobin

last: Lin

last: Zheng


title: AMPK attenuates SHH subgroup medulloblastoma growth and metastasis by inhibiting NF-kB activation

city: Nanjing

first: Cai

last: Jing

state: Jiangsu

address: dongshan street

department: Department of Medical Genetics

institute: Nanjing Medical University

summary: Background: Medulloblastoma (MB) is one of the most common malignant pediatric brain tumors. Metastasis and relapse are the leading causes of death in MB patients. The initiation of the SHH subgroup of MB (SHH-MB) is due to the aberrant activation of Sonic Hedgehog (Shh) signaling. However, the mechanisms for its metastasis are still unknown.   Results: AMP-dependent protein kinase (AMPK) restrains the activation of Shh signaling pathway, thereby impeding the proliferation of SHH-MB cells. More importantly, AMPK also hinders the growth and metastasis of SHH-MB cells by regulating NF-kB signaling pathway. Furthermore, Vismodegib and TPCA-1, which block the Shh and NF-kB pathways, respectively, synergistically restrained the growth, migration, and invasion of SHH-MB cells.   Conclusions: This work demonstrates that AMPK functions through two signaling pathways, SHH-GLI1 and NF-kB. AMPK-NF-kB axis is a potential target for molecular therapy of SHH-MB, and the combinational blockade of NF-kB and Shh pathways confers synergy for SHH-MB therapy.

overall_design: DAOY-siNC  DAOY-siPRKAA1

first: Shen

last: Yue

first: Jing

last: Cai


title: Gene expression changes between lenalidomide (LEN)-sensitive and LEN-resistant human multiple myeloma (MM) cell lines

city: Nagoya

first: Akinobu

last: Ota

state: Aichi

address: 1-1 Yazakokarimata

department: Food and Nutritional Environment

institute: Kinjo Gakuin University

summary: To investigate the relationship between the LEN resistance and gene expression profile, we generated LEN-resistant (LEN-R) cell clones using U266 and NCU-MM1 cell lines by chronically exposing low dose of LEN (0.1 to 10 μM). The parental and LEN-R MM cells were incubated with either DMSO or LEN (10 μM) for 24 h.

overall_design: MM cells were maintained in RPMI 1640 supplemented with 10% FBS at 37 ℃ in 5% CO2 humidified atmosphere.

first: Ichiro

last: Hanamura

first: Sivasundaram

last: Karnan


title: An evolutionarily conserved transcription factor controlling leaf vein growth in flowering plants (VDof1 ChIP-seq)

first: Wei

last: Hua

address: Xudong 2nd

institute: CAAS

summary: The veins of leaves are a highly evolved vascular network that allows plants to grow large and complex. The patterning process leading to their formation involves the integration of several internal and external signals, such as plant hormone auxin. Here, we show that an evolutionarily conserved transcription factor controlling leaf vein growth in flowering plants VDOF1 is dependent on autophagy for its activity in Arabidopsis thaliana leaf, suggesting that this pathway might be required for proper vascular system development in leaf. Taken together, our data forms that during leaf vein patterning there is presents a network in which a module that links VDOF1-ATG8-ANT1-SCR-SHR factors integrates Space-time dimension to provide more vein density, which establish a precondition for C4 photosynthesis transition.

overall_design: ChIP-seq was used to investigate the effect of VDof1 overexpression on the Arabidopsis thaliana genome. The results showed that VDof1 binds to a number of target genes, which may be involved in its regulatory effects.

first: Chen

last: Kuang

first: Xingchao

last: Sun

first: Jun

last: Liu


title: The homing behaviors of hair follicle dermal cells and cell intermigration between hair follicle and perifollicular microenvironment

city: Guangzhou

first: Yang

address: Nanfang Hospital

institute: Nanfang Hospital, Southern Medical University

summary: In our study, we found that skin depilation increased the number of DPCs and DSCs homing to HF niches. In order to screen out the chemokines upregulated after skin depilation, we carried out transcriptome analysis of mRNA expression profiles of depilated NOD/SCID skin sample at 0h, 1h, 4h, 12h, 1 days, 2 days, 4 days and 6 days after depilation.

overall_design: The mRNA expression profiles of skin sample at 0h, 1h, 4h, 12h, 1 days, 2 days, 4 days and 6 days after depilation were detected.

first: Kaitao

first: Fang

first: Ye

last: He

first: Zhiqi

last: Hu

first: Yong

last: Miao


title: Inter-organellar communication by a mitochondrial tRNA regulates nuclear metabolic transcription

city: New York

first: Christopher

last: Rouya

address: 1230 York Avenue

institute: Rockefeller University

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

overall_design: Refer to individual Series


title: Inter-organellar communication by a mitochondrial tRNA regulates nuclear metabolic transcription (GRO-Seq and CUT&RUN)

summary: To assess changes in HDAC2 genomic occupancy an transcription rate that occur upon mito-tRNA Asparagine inhibition, MDA-MB-231 cells were transfected with either a non-targeting control locked nucleic acid (LNA), or an LNA targeting mito-tRNA Asparagine.  HDAC2-bound loci were assessed using CUT&RUN, while transcriptional activity was assessed using GRO-Seq

overall_design: Transcriptomic, RNA-seq analysis in triplicate, comparing cells transfected with control, mito-tRNA Asparagine, or mito-tRNA Lysine LNAs

first: Sohail

last: Tavazoie


title: Amacrine cells suppress retinal ganglion cells survival and optic nerve regeneration bu releasing intersynaptic zinc

first: Jiahui

last: Tang

address: 7 Jinsui Road

institute: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University

summary: Retinal ganglion cells (RGCs) convey the major output of information collected from the eye to the brain. RGCs are irreversibly lost when injured in degenerative diseases such as glaucoma; this failure can be partially reversed by eliminating the retinal mobile zinc (Zn2+) and leads to substantial axon regeneration. ZnT3 conditional knockout in retinal amacrine cells blocks the synaptic transport of Zn2+, which promotes RGC survival and axonal regeneration in optic nerve jinjury (ONC). Here, we conducted an mRNA sequencing of flow cytometry-isolated RGCs 3 days after optic nerve injury with or without ZnT3 expression in retinal amacrine cells.

overall_design:
Ctrl: RGCs isolated from normal intact wild type retinas
ONC: RGCs isolated from optic nerve crush wild type retinas
CKO: RGCs isolated from optic nerve crush retinas with ZnT3 conditional knockout in amacrine cells

first: Zhe

first: Yiqing

last: Li