title: A cardiac developmental defect prevents thyroid hormone induced tachycardia in the syndrome of resistance to thyroid hormone alpha

status: Public on Apr 23 2023

city: Lübeck

first: Riccardo

last: Dore

state: Schleswig-Holstein

address: Ratzeburger Allee 160

department: Institute of Endocrinology and Diabetes

institute: University of Lübeck

summary: Purpose: the objective of this study was to determine cardiac gene expression profile in the mice heart of mutated thyroid receptor alpha 1 (TRα1R384C+/m) male offspring of control dams as well as of dams treated with 3,3',5-triiodo-L-thyronine (T3) from embryonic day 12.5 to 18.5

overall_design: Methods: wildtype females were mated to heterozygous TRα1R384C+/m males to obtain TRα1R384C+/+ or TRα1R384C+/m offspring. Dams were treated from embryonic day 12.5 to 18.5 with T3 via drinking water (0.5 mg/L), while the drinking water of control dams only contained 0.01% BSA. Offspring were NEVER treated and analyzed at 4 to 5 months.

first: Laura

last: Watson

first: Stefanie

last: Hollidge

first: Christin

last: Krause

first: Sarah

last: Sentis

first: Rebecca

last: Oelkrug

first: Cathleen

last: Geißler

first: Kornelia

last: Johann

first: Mehdi

last: Pedaran

first: Greta

last: Lyons

first: Nuria

last: Lopez-Alcantara

first: Julia

last: Resch

first: Friedhelm

last: Sayk

first: Karl

last: Iwen

first: Andre

last: Franke

first: Teide

last: Boysen

first: Jeffrey

last: Dalley

first: Kristina

last: Lorenz

first: Carla

last: Moran

first: Kirsten

middle: L

last: Rennie

first: Anders

last: Arner

first: Henriette

last: Kirchner

first: Krishna

last: Chatterjee

first: Jens

last: Mittag


title: Submicron-grooved films modulate the directional alignment and biological function of Schwann cells

city: Shenzhen

first: Zhen

last: Zhang

address: 1068 Xueyuan Avenue, Shenzhen University Town, Shenzhen, P.R.China

country: China

institute: Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences (CAS)

type: Expression profiling by high throughput sequencing

summary:
To investigate the differences in cell behavior and biological functions of Schwann cells on submicron grooved films and flat films, gene expression profiles of Schwann cells were analyzed.
We then performed gene expression profiling analysis using data obtained from RNA-seq of Schwann cells at 5 days.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for Schwann cells on submicron-grooved films and flat films.


title: Fast generation of left ventricle-like cardiomyocytes with mature properties from human pluripotent stem cells

status: Public on Apr 24 2023

city: London

first: Richard

middle: James

last: Mitter

state: LONDON

address: 1 Midland Road

department: Bioinformatics & Biostatistics

country: United Kingdom

institute: The Francis Crick Institute

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

overall_design: Refer to individual Series


first: Riccardo

last: Dore

country: Germany

type: Methylation profiling by genome tiling array

summary: Purpose: the objective of this study was to determine the whole DNA methylation profile in the mice heart of mutated thyroid receptor alpha 1 (TRα1R384C+/m) male offspring of control dams as well as of dams treated with 3,3',5-triiodo-L-thyronine (T3) from embryonic day 12.5 to 18.5

first: Laura

last: Watson

first: Stefanie

last: Hollidge

first: Christin

last: Krause

first: Sarah

middle: C

last: Sentis

first: Rebecca

last: Oelkrug

first: Cathleen

last: Geißler

first: Kornelia

last: Johann

first: Mehdi

last: Pedaran

first: Greta

last: Lyons

middle: A

middle: J

middle: W


title: Transcriptional Changes Associated with rotator cuff repair

status: Public on Apr 26 2023

city: La Jolla

first: Samuel

middle: Richard

last: Ward

state: CA

address: 9500 Gilman Drive (0863)

department: Orthopaedic Surgery, Radiology, and Bioengineering

country: USA

institute: University of California San Diego

summary: In this study, we collected rabbit supraspinatus muscle tissue with higher temporal resolution (1, 2, 4, 8 weeks)after 8 wk tear followed by repair (n=4/group), to determine time-depenet transcriptional changes after repair. RNA sequencing and analyses were performed using standard techniques to identify a transcriptional timeline of rotator cuff muscle changes and related morphological sequelae.

overall_design: rotator cuff muscle mRNA after tenotomy injury and repair at 1, 2, 4, 8 weeks

middle: S

last: Vasquez-Bolanos

first: Michael

last: Gibbons

first: Severin

last: Ruoss

first: Isabella

middle: T

last: Wu

first: Mary

last: Esparza

first: Donald

last: Fithian

first: Anshuman

last: Singh

first: Chanond

last: Nasamran

first: Kathleen

last: Fisch

middle: R


title: A cardiac developmental defect prevents thyroid hormone induced tachycardia in Resistance to Thyroid Hormone alpha

first: Riccardo

last: Dore

summary: Purpose: The objective of this study was to determine the cardiac gene expression prifile in the whole heart of mice with mutated thyroid receptor alpha 1 (TRα1R384C+/m) in control condition as well as after treatement with 3,3´,5-triiodo-L-thyronine (T3) for 12 days.

overall_design: Methods: 3-6 month old wildtype (n=12) and TRα1R384C+/m (n=10) male mice were housed at 30°C with ad libitum access to drinking tap water containing T3 (0.5 mg/L) for 12 days. Control groups had ad libitum access to drinking tap water. All four groups had ad libitum access to chow food.

first: Sarah Christine

last: Geissler

last: Ölkrug

first: Nuria

last: Lopez-Alcantara

first: Friedhelm

last: Sayk

first: Alexander

last: Iwen

first: Jeffrey

last: Dalley

first: Anders

last: Arner

first: Jens

last: Mittag

first: Laura

last: Watson

first: Stefanie

last: Hollidge

last: Krause

first: Julia

last: Resch

first: Andre

last: Franke

first: Teide Jens

last: Boysen

first: Henriette

last: Kirchner

first: Krishna

last: Chatterjee

first: Kristina

last: Lorenz

first: Carla

last: Moran

first: Kirsten

last: Rennie


title: Neonatal immune challenge poses a sex-specific risk for epigenetic microglial reprogramming and behavioral impairment

status: Public on Apr 21 2023

city: Freiburg im Breisgau

first: Omar

last: Mossad

address: Breisacher str 64

department: Institute of Neuropathology

institute: University Hospital Freiburg

summary: mRNA profiles of FACS-isolated microglia from brains of P7 & P40 mice. Mice were treated with repetitive doses of poly(I:C) between P2-P6. Each group contained 3-4 samples with a sequencing depth of 30M reads.

overall_design: Samples with different age groups and treatments.

first: Marius

last: Schwabenland

first: Thomas

last: Blank


title: Determine the differential miRNA levels in plasma of  methamphetamine addicts [array]

status: Public on Apr 20 2023

city: Ningbo

first: Wenjin

last: Xu

state: Zhejiang Province

address: 42 Xibei Street

institute: School of Medicine, Ningbo University,

summary: To determine the differential miRNA levels in methamphetamine addicts, we comparatively profiled plasma miRNA expression of methamphetamine abusers and healthy controls using Agilent Human miRNA Array.

overall_design: plasma miRNA expression of 5 methamphetamine abusers and 5 healthy controls


title: Paired single nucleus RNA and ATAC sequencing on the role of diet and aging in hematopoietic stem and progenitor cells

city: San Diego

first: Pura

last: Muñoz-Cánoves

address: 5510 Morehouse Dr

institute: Altos Labs

type: Genome binding/occupancy profiling by high throughput sequencing

summary: We performed joint single-nucleus RNA (snRNA-seq) and ATAC (snATAC-seq) sequencing on hematopoietic stem and progenitor cells (LSK) isolated from mouse bone marrow of mice of different ages and dietary treatments. Mice were either fed ad libitum continually until bone marrow isolation at young (yAL) or old (oAL) age, or underwent a mild dietary restriction (DR; 30% reduction in food intake by weight) for the two weeks prior to bone marrow isolation at young (yDR) or old (oDR) age to investigate early response to nutrient deprivation. Each of these four samples contained pooled cells from two mice.

overall_design: Profiles of single-nucleus transcriptomes and epigenomes, assayed using snRNA-seq and scATAC-seq, across sorted LSK cells from mouse bone marrow for mice of different diets and ages.

first: Marthe

last: Behrends

first: Yulin

last: Chen

first: Martin

last: Bens


title: Molecular basis for nuclear accumulation and targeting of the inhibitor of apoptosis BIRC2

city: Grand Rapids

first: Xiaobing

last: Shi

address: 333 Bostwick Ave. NE

institute: Van Andel Institute

summary: The inhibitor of apoptosis protein (IAP) BIRC2 regulates fundamental cell death and survival signaling pathways. Aberrant activity of BIRC2 is associated with immunological diseases, inflammation, and cancer. Unlike other IAPs, BIRC2 can localize to and function in the nucleus through unknown mechanisms. Here, we show that BIRC2 accumulates in the nucleus via binding of its second and third BIR domains, BIRC2BIR2 and BIRC2BIR3, to histone H3 tail and report the crystal structure of the BIRC2BIR3:H3 complex. RNA-seq analysis of cells in which the BIRC2 gene is knocked out by CRISPR/Cas9 reveals that the genes involved in the interferon and defense response signaling and the cell cycle regulation are most affected by depletion of BIRC2. Overexpression of BIRC2 delays DNA damage repair and recovery of the cell cycle progression and extends the etoposide-induced G2/M cell cycle arrest. We describe the structural mechanism for targeting of BIRC2BIR3 by a potent but biochemically uncharacterized small molecule inhibitor LCL161 and demonstrate that LCL161 disrupts the association of endogenous BIRC2 with H3 and readily stimulates cell death in cancer cells. We further show that LCL161 mediates degradation of BIRC2 in HIV-1 infected human CD4+ T cells. Our findings provide mechanistic insights into the nuclear accumulation of and blocking BIRC2.

overall_design: RNA profiles of sgRNA target GFP or BIRC2 transfected MCF7


title: Determine the differential miRNA levels in plasma exosomes of  methamphetamine addicts [miRNA-seq]

type: Non-coding RNA profiling by high throughput sequencing

summary: To determine the differential miRNA levels in methamphetamine addicts, we comparatively profiled plasma exosome miRNA expression of methamphetamine abusers and healthy controls using miRNA sequencing

overall_design: Plasma exosome miRNA expression of 5 methamphetamine abusers and 5 healthy controls


title: A biodegradable, flexible photonic patch for in vivo phototherapy

city: hangzhou

first: kaicheng

last: deng

state: zhejiang

address: sandun

institute: zhejiang university

summary: Therapeutic and diagnostic illumination on internal organs and tissues with high controllability and adaptability in terms of spectrum, area, depth, and intensity remains a major challenge. Here, we present a flexible, biodegradable photonic device iCarP featured with a micrometer scale air gap constructed between a refractive polyester patch and the embedded removable tapered optical fiber (TOF). ICarP combines the advantages of light diffraction by TOF, dual refractions on TOF/air and air/patch interfaces of the air gap, and reflection inside the patch to obtain a “bulb-like” illumination, guiding the light towards the target tissue. Large area, high intensity, wide spectrum, continuous/pulsatile, deeply penetrating illumination was achieved without puncturing the target tissues. ICarP supported phototherapies with different photosensitizers and achieved higher efficacy compared to optical fibers with clinically relevant optical fiber structures, attributed to the light scattering effect. The robust photonic device is compatible with thoracoscopy-based minimally invasive implantation and exhibited consistent performance on mechanically dynamic animal hearts in a demonstrative application of in situ photosynthesis for myocardial infarction treatment. The iCarP phototherapy improved survival of cardiac cells and preserved cardiac functions. These initial results showed that iCarP could be a safe, precise and widely applicable device suitable for internal organs/tissues illumination and associated therapy and diagnosis.

overall_design: Examination of the transcriptomes of rat heart tissue samples with the following treatments: n=4 MI, n=4 iCarP+/Light+, and n=4 Sham.

first: Yang

last: Zhu


title: miR-21 silencing is associated with gene changes in peritoneal macrophages

first: David

last: Chambers

state: London

address: Guy's Campus

department: Wolfson CARD

institute: King's College London

summary: Exosomes from sensory neurons overexpressing miR-21 induce a polarisation towards M1-like phenotype via down-regulation of TGF-B pathway.

overall_design: We used microarray analysis on peritoneal macrophages transfected with scramble control or antagomir-21, exposed to exosomes from sensory neurons overexpressing miR-21 or GFP-reporter

first: Malcangio

last: Marzia

first: George

last: Lampretsas

first: Lynda

last: Zeboudj


title: Dioxin-like compound exposures and DNA methylation in the Anniston Community Health Survey Phase II

city: Research Triangle Park

first: Xuting

last: Wang

state: NC

address: 111 TW Alexander Dr

institute: NIEHS/NIH

summary: In this epigenome-wide association study (EWAS), we examined the associations between PCDD, PCDF, and PCB exposures and DNA methylation. Whole blood DNA methylation was measured using Illumina EPIC arrays (n=292). We modeled lipid-adjusted toxic equivalencies (TEQs) for: ΣDioxins (sum of 28 PCDDs, PCDFs, cPCBs, and mPCBs), PCDDs, PCDFs, cPCBs, and mPCBs using robust multivariable linear regression adjusting for age, race, sex, smoking, total lipids, and estimated percentages of six blood cell types.

overall_design: The Anniston Community Health Survey (ACHS-I) was initially conducted from 2005-2007 to assess PCB exposures in Anniston, Alabama residents. In 2014, a follow-up study (ACHS-II) was conducted to measure the same PCBs as in ACHS-I and additional compounds e.g., polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like non-ortho (cPCBs) substituted PCBs. The primary objective of this study was to carry out an epigenome-wide association study (EWAS) assessing if exposures to AHR ligands such as, PCDDs, PCDFs, cPCBs, and mPCBs, were associated with altered methylation at any genome-wide CpGs.

first: Douglas

last: Bell

first: Gary

last: Pittman

first: Michelle

last: Campbell

first: Sherry

last: Coulter

first: James

last: Olson

first: Marian

last: Pavuk

first: Linda

last: Birnbaum


title: Exercise reprograms the inflammatory landscape of multiple stem cell compartments during mammalian aging I

status: Public on Apr 19 2023

city: Palo Alto

first: Ling

last: Liu

address: 300 Pasteur Drive

institute: Stanford University

summary: To gain insight into the mechanisms by which exercise affects muscle stem cell niche, we subjected young and old mice to aerobic exercise and performed whole transcriptome analysis of muscle cells from these animals.

overall_design: Myofibers stripped of attaching mononucleated cells were isolated from exercised or control young (4-month old) and old (22-month old) mice and processed for RNA-seq.

first: Thomas

last: Rando


title: The HSV-1 ICP22 protein selectively impairs histone repositioning upon Pol II transcription downstream of genes (RNA-seq)

city: München

first: Caroline

last: Friedel

address: Amalienstr. 17

department: Institut für Informatik

institute: Ludwig-Maximilians-Universität München

summary: Primary human fetal foreskin fibroblasts (HFFF) were infected with the ICP22-null mutant of HSV-1 and HSV-1 Wt strain F at a multiplicity of infection (MOI) of 10 for 8 and 12 hpi. Cells were treated for 8 or 12 hours with the phosphonoacetic acid (PAA) (350ug/ml). Total cellular RNA was isolated using Trizol. T-HF cells were grown either in the presence or absence of DOX. Upon DOX exposure, cells expressed either HA-ICP22 or HA-ICP22 and V5-ICP27. T-HF HA-ICP22 cells were treated with 80 mM KCl (salt stress) for 2 hours before collecting the total RNA. Total cellular RNA was isolated using Trizol.

overall_design: Primary human fetal foreskin fibroblasts (HFFF) were infected with the ICP22-null mutant of HSV-1 and HSV-1 Wt strain F at a multiplicity of infection (MOI) of 10 for 8 and 12 hpi. Total cellular RNA was isolated using Trizol. T-HF cells were grown either in the presence or absence of DOX. Upon DOX exposure, cells expressed either HA-ICP22 or HA-ICP22 and V5-ICP27. T-HF HA-ICP22 cells were treated with 80 mM KCl (salt stress) for 2 hours before collecting the total RNA. Total cellular RNA was isolated using Trizol.

first: Lara

last: Djakovic

last: Hennig

first: Katharina

last: Reinisch

first: Andrea

last: Milic

first: Adam

last: Whisnant

last: Wolf

first: Elena

last: Weiß

first: Tobias

last: Haas

first: Arnhild

last: Grothey

first: Christopher

last: Jürges

first: Michael

last: Kluge

first: Florian

last: Erhard

first: Lars

last: Dölken


title: AtBRO1, BRO1-like domain-containing protein, modulates growth and abiotic stress responses in Arabidopsis

status: Public on Apr 18 2023

city: Poznan

first: Michał

last: Szcześniak

address: Uniwersytetu Poznanskiego 6

department: Institute of Human Biology and Evolution

country: Poland

institute: Adam Mickiewicz University

summary: Plants physiological mechanisms are affected by Abscisic acid (ABA) via changing gene expression and empowers plants to adapt in numerous environments. Plants have evolved their protection mechanisms for seed germination and abiotic environments to deal with critical harsh conditions. Here, we have explored those changes in Arabidopsis thaliana plants subjected to multiple abiotic stresses. AtBro1 transcripts showed up-regulation in the presence of salt, ABA and mannitol stress conditions. AtBRO1 over-expression lines exhibited robust tolerance to drought and salt stress. Further, ABA elicits resistance responses in loss-of-function bro1-1 mutant plants and AtBro1 positively regulates drought resistance in Arabidopsis. Promoter of AtBro1 fused with GUS showed GUS expression mainly in the rosette leaves and floral clusters, especially in anthers. AtBro1 protein was found to be localized in the plasma membrane of Arabidopsis at the subcellular level by using AtBro1::GFP fusion. Using a broad RNA-sequencing analysis, we observed that early transcriptional responses prompted by ABA induction exhibit specific quantitative differences at different time points, suggesting that ABA stimulates resistance responses in bro1-1 mutant plants. Additionally, transcripts levels of MOP9.5, MRD1, HEI10, and MIOX4 were altered in loss-of-function mutant plants which are involved in different stress conditions.  Collectively, our results have shown that AtBro1 is involved in a significant role by regulating plant transcriptional response to ABA and induction of resistance response against abiotic stress.

overall_design: Seeds of WT Arabidopsis thaliana, Columbia ecotype (Col-0), as well as bro1-1 mutant were used in this study. After two days of stratification at 4°C, the plants were grown in Half Murashige and Skoog Basal Medium supplemented with sucrose. Seedlings were grown weeks for two weeks, then treated with ABA (100 µM) for 2 and 4 hours. The harvested plant materials were freezed in liquid nitrogen and stored in -80°C freezer until further use. For each condition (mock and ABA treated), three independent biological replicates were used and total RNA was extracted using RNAeasy kit (Qiagen) according to the manufacturer’s protocol. And samples were used for mRNA sequencing.

first: Syed

middle: M

last: Muntazir Mehdi

first: Agnieszka

last: Ludwików


title: Exercise reprograms the inflammatory landscape of multiple stem cell compartments during mammalian aging IV

first: Ling

last: Liu

summary: To gain insight into the mechanisms by which exercise affects the muscle stem cell compartment, we subjected young and old mice to aerobic exercise and performed single cell transcriptome analysis of mononucleated cells from hindlimb muscles of these animals.

overall_design: Total mononucleated cells were isolated from hindlimb muscles of exercised or control young (4-month old) and old (22-month old) mice and processed for single cell RNA-seq.

last: Rando


title: Exercise reprograms the inflammatory landscape of multiple stem cell compartments during mammalian aging II

summary: To gain insight into the mechanisms by which exercise affects circulating immune cells, we subjected young and old mice to aerobic exercise and performed single cell transcriptome analysis of circulating immune cells from these animals.

overall_design: Circulating immune cells were isolated from the blood of exercised or control young (4-month old) and old (22-month old) mice and processed for single cell RNA-seq.

first: Thomas


title: INTAC endonuclease and phosphatase modules differentially regulate transcription by RNA polymerase II

city: Shanghai

first: Linna

last: Peng

address: Dong'an Road

institute: Fudan University

summary:
Gene expression in metazoans is controlled by promoter-proximal pausing of RNA polymerase II, which can undergo productive elongation or early termination. Integrator-PP2A (INTAC) plays a crucial role in determining the fate of paused polymerases, but the underlying mechanisms remain unclear. Here we establish a rapid degradation system to dissect the direct functions of INTAC RNA endonuclease and phosphatase modules. We find that both catalytic modules function at most if not all active promoters and enhancers, yet differentially affect polymerase fate. The endonuclease module induces early termination, with its disruption leading to accumulation of non-competent polymerases and downregulation of highly expressed genes, while competent polymerases accumulate at lowly expressed genes and non- coding elements, leading to their upregulation. The phosphatase module primarily prevents the release of paused polymerases and limits transcriptional activation, especially for highly paused genes. Thus both INTAC’s catalytic modules have unexpectedly general yet distinct roles in dynamic transcriptional control.

This SuperSeries is composed of the SubSeries listed below.

overall_design: We performed PRO-seq, ChIP-seq, or TT-seq to investigate the role of INTAC in regulating transcription.


title: A Bipartate function of ESRRB integrates signaling over time to balance self-renewal and differentiation [scRNA-Seq]

city: Copenhagen

first: Josh

last: Brickman

address: 3B Blegdamsvej

department: reNEW

country: Denmark

institute: Copenhagen University

summary: Cooperative DNA binding of transcription factors (TFs) integrates external stimuli and context across tissues and time. Naïve mouse embryonic stem cells (ESCs) are derived from early development and can sustain early embryonic pluripotent identity indefinitely. Here we ask whether TFs associated with pluripotency evolved to directly support this state or if it emerges from their combinatorial action? NANOG and ESRRB are key pluripotency factors that co-bind DNA. We find that when both factors are expressed at physiological levels, ESRRB supports pluripotency. However, when NANOG is not present, ESRRB supports a bistable culture of embryo-like primitive endoderm identity ancillary to pluripotency. The stochiometry between these factors quantitatively influences differentiation and in silico modelling of bipartite TF activity suggests ESRRB safeguards plasticity in differentiation. Thus the concerted activity of cooperative TFs transforms their effect to sustain intermediate cell identities that can be expanded ex vivo as highly stable stem cell models.

overall_design: scRNA-Seq

first: Teresa

middle: E

last: Knudsen

first: William

last: Hamilton

first: Maria

last: Nicolaisen

first: Martin

last: Proks

first: Alexander

middle: V

last: Nielsen

first: Ala

last: Trusina

first: Joshua


title: A Bipartate function of ESRRB integrates signaling over time to balance self-renewal and differentiation

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

overall_design: Refer to individual Series


title: The cell wall lipoprotein CD1687 acts as a DNA binding protein during deoxycholate-induced biofilm formation in Clostridioides difficile

city: Paris

first: Monot

last: Marc

address: 25, rue du docteur roux

department: Genomes and Genetics

country: France

institute: Institut Pasteur

summary: The ability of bacterial pathogens to establish recurrent and persistent infections is frequently associated with their ability to form biofilms. Clostridioides difficile infections have a high rate of recurrence and relapses and it is hypothesised that biofilms are involved in its pathogenicity and persistence. Biofilm formation by C. difficile is still poorly understood. It has been shown that specific molecules such as deoxycholate (DCA) or metronidazole induce biofilm formation, but the mechanisms involved remain elusive. In this study, we describe the role of the lipoprotein CD1687 in the DCA-induced biofilm formation of C. difficile. We showed that the expression of CD1687, which is part of an operon within the CD1685-CD1689 gene cluster, is controlled by multiple transcription starting sites induced for some of them in response to DCA. Only CD1687 is required for biofilm formation and the overexpression of CD1687 is sufficient to induce biofilm formation. Using RNAseq analysis, we showed that CD1687 affects the expression of transporters and metabolic pathways and we identified several potential binding partners by pull-down assay, including transport-associated extracellular proteins. We then demonstrated that CD1687 is surface exposed in C. difficile, and this localization is required for DCA-induced biofilm formation. Given this localization and that C. difficile forms eDNA-rich biofilms, we confirmed that CD1687 binds DNA in a non-specific manner. We thus hypothesize that CD1687 is a component of the downstream response to DCA leading to biofilm formation by promoting interaction between the cells and the biofilm matrix by binding eDNA.

overall_design: Total RNA was extracted from 4 independent biological replicates of 630 C. difficile strains at 4 conditions with 240µM Deoxycholate for the 1687 mutant and the wild type strains and with plasmid empty or that contains the 1687 gene.

first: Emile

last: Auria

first: Juliana

middle: P

last: Da Fonseca

first: Marc

last: Monot


title: Cytolytic CD8+ T cells infiltrate germinal centers to limit ongoing HIV replication in spontaneous controller lymph nodes

city: Cambridge

first: Jonathan

middle: Morris

last: Urbach

state: Massachusetts

address: 400 Technology Sq Rm 851

institute: Ragon Institute of MGH, MIT and Harvard

summary: Follicular CD8+ T cells (fCD8) mediate surveillance in lymph node (LN) germinal centers against lymphotropic infections and cancers, but precise mechanisms by which these cells mediate immune control remain incompletely resolved. To address this, we investigated functionality, clonotypic compartmentalization, spatial localization, phenotypic characteristics, and transcriptional profiles of LN-resident virus-specific CD8+ T cells in persons who control HIV without medications. Antigen-induced proliferative and cytolytic potential consistently distinguished spontaneous controllers from noncontrollers. T cell receptor analysis revealed complete clonotypic overlap between peripheral and LN-resident HIV-specific CD8+ T cells. Transcriptional analysis of LN CD8+ T cells revealed gene signatures of inflammatory chemotaxis and antigen-induced effector function. In HIV controllers, the cytotoxic effectors perforin and granzyme B were elevated among virus-specific CXCR5+ fCD8s proximate to foci of HIV RNA within germinal centers. These results provide evidence consistent with cytolytic control of lymphotropic infection supported by inflammatory recruitment, antigen-specific proliferation, and cytotoxicity of fCD8s.

overall_design: HIV-specific CD8+ T cell mRNA profiles in contemporaneous matched peripheral blood (PB) and inguinal lymph node (LN)

first: David

last: Collins

first: Julia

last: Hitschfel

first: Umar

last: Arshad

first: Bruce

last: Walker


title: Intestinal transcriptome profiles of ND and WD-fed Tas1r3−/− and Wild Type mice using RNA-seq analysis

city: Seoul

first: Woo-Jeong

last: Shon

address: 103 Daehak-ro, Jongno-gu,

department: College of Medicine

country: South Korea

institute: Seoul National University

summary:
Purpose: Excessive intake of a western diet (WD), characterized by high fat and sugary drinks, is hypothesized to contribute to the development of inflammatory bowel disease (IBD). Despite the identified clinical association, the molecular mechanisms through which dietary changes lead to IBD development remain unknown. Here, we generated a murine model of severe intestinal inflammation triggered by long-term WD consumption, which exhibited markedly elevated taste receptor TAS1R3 expression in inflamed bowel tissues. Thus, we hypothesized that nutrient-induced TAS1R3 modulation is central to regulating intestinal inflammation. We tested our hypothesis by analyzing changes in gene expression profiles and inflammatory cell infiltration in the inflamed bowel tissues of WD-fed Tas1r3-deficient mice.
Methods: We carried out RNA-Seq of ileum tissue of wild-type (WT) and taste receptor Tas1r3 knockout (Tas1r3−/−) mice fed a normal diet (ND) or western diet (WD) for 10 weeks using Ion Proton System. Raw RNA-seq reads were split into individual samples based on barcodes and quality controlled using the FASTQC tool. The reads were analyzed with Partek Flow software (Partek, St. Louis, MI, USA) (http://www.partek.com/partekgs). The sequence reads that passed quality filters were analyzed at the transcript isoform level.
Results: We confirmed that Tas1r3-deficient mice are protected from WD-induced intestinal inflammation. Consistent with little or no phenotypic change in the ND group, the gene expression profiles from the ND-fed Tas1r3−/− and WT mice were similar, whereas the ileal transcriptome profiles from the WD-fed Tas1r3−/− mice were readily distinguishable from those of WD-fed WT mice. Inflammatory cytokines such as Tnfα and Il1b were highly expressed in WD-fed WT mice, whereas Pparg, Tjp3, and Defa27 were highly expressed in WD-fed Tas1r3−/− mice. Importantly, we confirmed that the absence of TAS1R3 caused a significant reduction in the inflammatory response-related signaling pathway; GSEA plots also revealed that the mTOR signaling pathway was greatly suppressed. Most notably, the PPAR signaling pathway was significantly affected by TAS1R3 absence. GSEA confirmed that genes associated with the PPAR signaling pathway were significantly enriched in the set of DEGs between Tas1r3−/− and WT mice in the WD groups.
Conclusion: Our data suggest that, due to its suppressive action on mTOR, TAS1R3 might function as an important regulator of the PPAR-γ signaling pathway in the intestinal tract.

overall_design: ileal mRNA profiles of WT and taste receptor Tas1r3 knockout (Tas1r3−/−) mice fed ND or WD for 10 weeks

first: Dong-Mi

last: Shin


title: A Bipartate function of ESRRB integrates signaling over time to balance self-renewal and differentiation [ChIP-Seq]

first: Josh

last: Brickman

overall_design: ChIP-Seq 12 samples

first: Teresa

last: Knudsen

first: William


title: Exercise reprograms the inflammatory landscape of multiple stem cell compartments during mammalian aging III

first: Ling

last: Liu

summary: To gain insight into the mechanisms by which exercise affects hematopoietic stem cells, we subjected young and old mice to aerobic exercise and performed single cell transcriptome analysis of hematopoietic progenitors in the bone marrow of these animals.

overall_design: Hematopoietic progenitors were isolated from the bone marrow of exercised or control young (4-month old) and old (22-month old) mice by FACS and processed for single cell RNA-seq.

first: Thomas

last: Rando


title: A Bipartate function of ESRRB integrates signaling over time to balance self-renewal and differentiation [RNA-Seq]

overall_design: RNA-Seq 9 samples

last: Hamilton

first: Maria

last: Nicolaisen

first: Martin

last: Proks

first: Alexander

last: Nielsen

first: Ala

first: Joshua


title: A Bipartate function of ESRRB integrates signaling over time to balance self-renewal and differentiation [ATAC-Seq]

overall_design: ATAC-Seq 12 samples

last: Trusina


title: Intranasal Insulin Treatment Alters Gene Expression Profile in the Hippocampus of Rats with Perinatal Iron Deficiency

city: Minneapolis

first: Chris

middle: H

last: Wendt

state: MN

address: 420 Delaware St SE

department: Medicine

institute: University of Minnesota

summary: Background: Perinatal iron deficiency (ID) targets the hippocampus and leads to long-term cognitive deficits. These deficits remain even after iron repletion, suggesting that further insight into the mechanisms of cognitive deficits and adjunct treatments are needed. Intranasal insulin improves cognitive deficits in adult humans with Alzheimer’s disease and type 2 diabetes and could provide benefits in ID-induced neurological dysfunction. Objective: Assess the effects of intranasal insulin administration on the hippocampal transcriptome in rat model of perinatal ID. Methods: Perinatal ID was induced using a low iron diet from gestational day 3 until postnatal day (P) 7, followed by an iron sufficient (IS) diet through P21. Intranasal insulin was administered at a dose of 0.3 IU, twice daily from P8 to P21. Hippocampi were removed on P21 from IS control, ID control, IS insulin, and ID insulin groups. Total RNA was isolated and profiled using TruSeq next-generation sequencing (Illumina). Gene expression profiles were characterized using custom Galaxy workflows and expression patterns were examined using Ingenuity Pathways Analysis (Qiagen) (n = 7-9 per group). Results: Transcriptomic profiling revealed that mitochondrial biogenesis and flux, oxidative phosphorylation, quantity of neurons, CREB signaling in neurons, and RICTOR-based mTOR signaling were disrupted with ID and positively affected by insulin treatment with the most benefit observed in the ID insulin group. Conclusions: Both perinatal ID and insulin administration altered gene expression in the developing hippocampus. Intranasal insulin treatment reversed the adverse effects of ID on many molecular pathways and should be further explored as an adjunct therapy in perinatal ID.

overall_design: Iron deficienct rat pups were treated with intranasal insulin and compared with iron sufficent controls through RNA-seq profiling of the hippocampus.

first: Brian

last: Sandri

first: Kathleen

last: Ennis-Czerniak

first: Priya

last: Kanajam

last: Frey II

first: Eric

middle: F

last: Lock

first: Raghavendra

middle: B

last: Rao


title: Multiomic Approach Characterises the Neuroprotective Role of Retromer in Regulating Lysosomal Health

status: Public on Apr 17 2023

city: Santander

first: Lucio

last: Di Filippo

state: Cantabria

address: PCTCAN - Cl. Albert Einstein, 22

country: Spain

institute: IBBTEC

summary: Retromer controls cellular homeostasis through regulating integral membrane protein sorting and transport and by controlling maturation of the endo-lysosomal network. Retromer dysfunction, which is linked to neurodegenerative disorders including Parkinson’s and Alzheimer’s diseases, manifests in complex cellular phenotypes, though the precise nature of this dysfunction, and its relation to neurodegeneration, remain unclear. Here, we perform the first integrated multiomics approach to provide precise insight into the impact of Retromer dysfunction on endo-lysosomal health and homeostasis within a human neuroglioma cell model. We quantify profound changes to the lysosomal proteome, indicative of broad lysosomal dysfunction and inefficient autophagic lysosome reformation, coupled with a reconfigured cell surface proteome and secretome reflective of increased lysosomal exocytosis. Through this global proteomic approach and parallel transcriptomic analysis, we provide an unprecedented integrated view of Retromer function in regulating lysosomal homeostasis and emphasise its role in neuroprotection.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for wild-type H4 cells, three VPS35 KO clones, and three corresponding VPS35 KO clones rescued with VPS35-GFP expression

first: James

last: Daly

last: Danson

first: Davide

last: Cacchiarelli

first: Andrea

last: Ballabio

first: Peter

last: Cullen


title: Genome-wide analysis of RNA binding proteins co-expression with alternative splicing events in mitral valve prolapse

city: Nanjing

first: Yanhu

last: Wu

state: Jiangsu Province

address: 300 Guang Zhou Road, Nanjing, Jiangsu Province, China

institute: Jiangsu Province People's Hospital

summary: For RNA extraction, we obtained peripheral blood mononuclear cells (PBMCs) from 5 patients with mitral valve prolapse (MVP), with or without chordae tendineae rupture, and 5 healthy individuals. High-throughput sequencing was used for RNA-sequencing.

overall_design: We investigated the possible role and molecular mechanisms of RNA binding proteins (RBPs) and their regulated alternative splicing events (RASEs) in the potential pathogenesis of mitral valve prolapse (MVP).

first: Zhao

last: Meng

first: Wu

last: Yanhu

first: Chen

last: Liang

first: Zhou

last: Jingxin


title: C-tail hyperphosphorylation activates PTEN oncogenic properties

city: Rochester

first: Hu

last: Li

address: 200 1st St SW

institute: Mayo Clinic

summary: PTEN is a multifaceted tumor suppressor that is highly sensitive to alterations in expression or function. The PTEN C-tail domain, which is rich in phosphorylation sites, has been implicated in PTEN stability, localization, catalytic activity, and protein interactions, but its role in tumor suppression remains unknown. To address this, we utilized several mouse strains with nonlethal C-tail mutations. Analysis of mice containing nonphosphorylatable or phosphomimetic versions of S380, a C-tail residue hyperphosphorylated in human gastric cancers, reveals that PTEN stability and ability to inhibit PI3K-AKT depends on dynamic phosphorylation-dephosphorylation of this residue. While phosphomimetic S380 drives neoplastic growth in prostate by promoting nuclear accumulation of β-catenin, nonphosphorylatable S380 is not tumorigenic. These data suggest that C-tail hyper-phosphorylation creates oncogenic PTEN and is a potential target for anti-cancer therapy.

overall_design: 3 prostates of each genotype: WT, Pten S380A/S380A and Pten S380D/S380D

first: Janine

last: Van Ree

first: Jan

last: Van Deursen


title: Targeting SWI/SNF ATPases in H3.3K27M Diffuse Intrinsic Pontine Gliomas [ATAC-Seq]

status: Public on Apr 16 2023

city: Ann Arbor

first: Sriram

last: Venneti

state: MI

address: 1500 East Medical Center Drive

department: MM Pathology Department

institute: University of Michigan

summary: Diffuse midline gliomas (DMGs), including diffuse intrinsic pontine gliomas (DIPGs), bearing lysine-to-methionine mutations in histone H3 at lysine 27 (H3K27M) are lethal childhood brain cancers. These tumors harbor a global reduction in the transcriptional repressive mark H3K27me3 accompanied by an increase in the transcriptional activation mark H3K27ac. We postulated that H3K27M mutations, in addition to altering H3K27 modifications, reprogram the master chromatin remodeling SWI/SNF complex. The SWI/SNF complex can exist in two main forms termed BAF and PBAF that play central roles in neurodevelopment and cancer. Moreover, BAF antagonizes PRC2, the main enzyme catalyzing H3K27me3. We demonstrate that H3K27M gliomas show increased protein levels of the SWI/SNF complex ATPase subunits SMARCA4 and SMARCA2 and the PBAF component PBRM1. Additionally, knockdown of mutant H3K27M lowered SMARCA4 protein levels. The proteolysis targeting chimera (PROTAC) AU-15330 that simultaneously targets SMARCA4, SMARCA2, and PBRM1 for degradation exhibits cytotoxicity in H3.3K27M but not H3 wild-type cells. AU-15330 lowered chromatin accessibility measured by ATAC-seq at non-promoter regions and reduced global H3K27ac levels. Integrated analysis of gene expression, proteomics, and chromatin accessibility in AU-15330-treated cells demonstrated reduction in levels of FOXO1, a key member of the forkhead family of transcription factors. Moreover, genetic or pharmacologic targeting of FOXO1 resulted in cell death in H3K27M cells. Overall, our results suggest that H3K27M upregulates SMARCA4 levels and combined targeting of SWI/SNF ATPases in H3.3K27M can serve as a potent therapeutic strategy for these deadly childhood brain tumors.

overall_design: Comparative chromatin accessibility (ATAC) profiles of DIPG007 treated with DMSO or AU15330 (SMARCA2/4 PROTAC) for 24h at 1mM.

first: Mateus

last: Mota

first: Abhijit

last: Parolia

first: Eleanor

last: Young


title: Cell state-dependent chromatin targeting in NUT carcinoma

status: Public on Apr 14 2023

city: BOSTON

first: MITZI

middle: I

last: KURODA

state: MA

address: 77 Ave Louis Pasteur NRB 168

department: Genetics

institute: Brigham & Women's Hospital / Harvard Medical School

summary:
ChIP-seq profiles of BRD4-NUT in HUES64 & HUES64 derived mesoderm (dME).
ChIP-seq profiles of BRD4-NUT in Ntera-2 (NT2) cells & Ntera-2 (NT2) differentiated cells after 4 hr and 16 hr  retinoic acid treatment..

overall_design: ChIP-seq

first: A

last: Alekseyenko

first: M

last: Kuroda

first: Z

last: Dhoondia

first: Jessica

middle: L

last: Makofske


title: Targeting SWI/SNF ATPases in H3.3K27M Diffuse Intrinsic Pontine Gliomas [RNA-Seq]

overall_design: Comparative RNA profiles of DIPG007 treated with DMSO or AU15330 (SMARCA2/4 PROTAC) for 24h at 1mM.


title: Integrative genomic analyses in adipocytes implicate DNA methylation in human obesity and diabetes

city: London

first: William

middle: Robert

last: Scott

address: Hammersmith Hospital, Du Cane Road

department: Institute of Clinical Sciences

institute: Imperial College London

summary: DNA methylation variations are prevalent in human obesity but evidence of a causative role in disease pathogenesis is limited. Here, we combine epigenome-wide association and integrative genomics to investigate the impact of adipocyte DNA methylation variations in human obesity. We discover extensive DNA methylation changes that are robustly associated with obesity (N=190 samples, 691 loci in subcutaneous and 173 loci in visceral adipocytes, P<1x10-7). We connect obesity-associated methylation variations to transcriptomic changes at >500 target genes, and identify putative methylation-transcription factor interactions. Through Mendelian Randomisation, we infer causal effects of methylation on obesity and obesity-induced metabolic disturbances at 59 independent loci. Targeted methylation sequencing, CRISPR-activation and gene silencing in adipocytes, further identifies regional methylation variations, underlying regulatory elements and novel cellular metabolic effects. Our results indicate DNA methylation is an important determinant of human obesity and its metabolic complications, and reveal mechanisms through which altered methylation may impact adipocyte functions.

overall_design: We characterised genome-wide DNA methylation in two independent cohorts. Cohort one comprised 48 adipocyte samples (24 subcutaneous and 24 visceral) from people with extreme obesity and 48 adipocyte samples from healthy controls (24 subcutaneous and 24 visceral) analysed using the Illumina Infinium HumanMethylation450 BeadChip (Discovery Cohort). Cohort two comprised 48 adipocyte samples (24 subcutaneous and 24 visceral) from people with extreme obesity and 48 adipocyte samples from healthy controls (24 subcutaneous and 24 visceral) analysed using the Illumina Infinium EPIC BeadChip (Replication Cohort). Adipocytes were isolated from fresh whole subcutaneous and visceral adipose tissue samples using collagenase digestion and flotation, and stored at -80C, prior to DNA extraction and bisulfite conversion with 0.2-0.5-mcg of genomic DNA.

first: Liam

last: McAllan

first: Damir

last: Baranašić

first: Sergio

last: Villicaña

first: Scarlett

last: Brown

first: Weihua

last: Zhang

first: Benjamin

last: Lehne

first: Marco

last: Adamo

first: Andrew

last: Jenkinson

first: Mohamed

last: Elkalaawy

first: Borzoueh

last: Mohammadi

first: Majid

last: Hashemi

first: Nadia

last: Fernandes

first: Nathalie

last: Lambie

first: Richard

last: Williams

first: Colette

last: Christiansen

first: Youwen

last: Yang

first: Liudmila

last: Zudina

first: Vasiliki

last: Lagou

first: Sili

last: Tan

first: Juan

last: Castillo-Fernandez

first: James

last: King

first: R.

last: Soong

first: Paul

last: Elliott

first: Inga

last: Prokopenko

first: Ines

last: Cebola

first: Marie

last: Loh

first: Boris

last: Lenhard

first: Rachel

last: Batterham

first: Jordana

last: Bell

first: John

middle: C

last: Chambers

first: Jaspal

last: Kooner


title: Targeting SWI/SNF ATPases in H3.3K27M Diffuse Intrinsic Pontine Gliomas

first: Sriram

last: Venneti


title: Eubacterium rectale improves the efficacy of anti-PD1 immunotherapy in melanoma via L-serine-mediated NK-cell activation

city: Changsha

first: Nian

last: Liu

state: Hunan

address: Xiangya road 87#

department: Department of Dermatology

institute: Xiangya Hospital, Central South University

summary: NK cells, as a type of key immune cell, play essential roles in tumor cell immune escape and immunotherapy. Accumulating evidence has demonstrated that the gut microbiota community affects the efficacy of anti-PD1 immunotherapy and that remodeling the gut microbiota structure is a promising strategy to enhance anti-PD1 immunotherapy responsiveness in advanced melanoma patients; however, the details of the mechanism remain elusive. In this study, we found that Eubacterium rectale (E. rectale) was significantly enriched in melanoma patients who responded to anti-PD1 immunotherapy and a high E. rectale abundance was related to longer survival in melanoma patients. Furthermore, administration of E. rectale remarkably improved the efficacy of anti-PD1 therapy and benefited the overall survival of tumor-bearing mice; moreover, application of E. rectale significantly recruited NK cells into the tumor microenvironment. Interestingly, conditioned medium isolated from an E. rectale culture system dramatically enhanced NK-cell function. Through GC-MS/ UHPLC-MS/MS-based metabolomic analysis, L-serine production was found to be significantly decreased in the E. rectale group; moreover, administration of an L-serine synthesis inhibitor dramatically increased NK-cell activation, which led to enhanced anti-PD1 immunotherapy effects. Mechanistically, supplementation with L-serine or application of the L-serine synthesis inhibitor affected NK-cell activation through Fos/Fosl. In summary, our findings reveal the role of bacteria-modulated serine metabolic signaling in NK-cell activation and provide a novel therapeutic strategy to improve the efficacy of anti-PD1 immunotherapy in melanoma.

overall_design: NK92 cells treated with L-serine(1mM/L) or NCT503 (40μM/L) for 48 hours.NCT503 is an inhibitor of L-serine Synthesis.

first: Lihui

last: Chen

first: Xiang

first: Cong

last: Peng


title: CPD-capture-seq map of CPD formation in UV-irradiated primary melanocytes, normal human skin fibroblasts and UV-irradiated genomic DNA

status: Public on Apr 12 2023

city: Pullman

middle: J.

last: Wyrick

state: WA

address: Biotechnology Life Sciences 241

department: School of Molecular Biosciences

institute: Washington State University

type: Genome variation profiling by high throughput sequencing

summary: UV-induced CPDs were mapped in primary skin melanocytes or normal human skin fibroblasts following either UVC or UVB irradiation and in isolated human genomic DNA (naked DNA control) that was UVB or UVC irradiated. CPDs were mapped across the human genome using the CPD-capture-seq method and the resulting libraries were captured for ~4000 genomic regions of interest (~3 Mbp) of the human genome by the company Rapid Genomics prior to Illumina sequencing

overall_design: A method known as CPD-capture-seq was used to map the formation of UV-induced CPDs across the genome of primary human melanocytes (NHEM 2) and normal human skin fibroblasts (NHF1) cells after they were irradiated with a UVB or UVC light. As a control experiment, isolated human genomic DNA was irradiated with UVB or UVC light (naked DNA control) and CPDs were mapped using CPD-capture-seq and the resulting libraries were captured for ~4000 genomic regions of interest (~3 Mbp) of the human genome by the company Rapid Genomics prior to Illumina sequencing

first: Kathiresan

last: Selvam


title: RNA Polymerase II transcription independent of TBP [NET-seq]

city: Vancouver

first: Sheila

last: Teves

state: BC

address: 2350 Health Sciences Mall

department: Biochemistry

country: Canada

institute: Life Science Institute

summary: Using NET-seq to profile nascent RNA transcription, we show that auxin-mediated depletion of TBP does not affect Pol II transcription and gene activation via heat shock.

overall_design: NET-seq analysis was performed in mouse embryonic stem cells, and is comprised of two biological replicates of untreated cells, auxin treated cells, heat shocked cells, and heat shocked + auxin treated cells (8 samples total).

first: James

middle: Z

last: Kwan

first: Thomas

last: Nguyen

first: Anuli

last: Uzozie

first: Marek

middle: A

last: Budzyński

first: Jieying

last: Cui

first: Joseph

last: Lee

first: Filip

last: Van Petegem

first: Philipp

last: Lange


title: RNA Polymerase II transcription independent of TBP (CUT&Tag)

summary: Using CUT&Tag, a chromatin profiling technique, we show that TBP depletion via IAA surprisingly does not affect RNA Pol II transcription but affects RNA Pol III transcription. Additionally, induction of genes via heat shock and retinoic acid treatment does not require TBP. We also show that a metazoan specific paralog TRF2 does not compensate for TBP for RNA Pol II transcription and that the TFIID subunit of the Pre-initiation Complex can still form with specific subunits still binding onto DNA when TBP is depleted.

overall_design: Chromatin profiling was done for Pol II, Pol III, TBP, TAF1, TAF4 and TFIIA in mESCs for control, IAA, HS, HSIAA, RA, RAIAA with at least 2 replicates for each condition

middle: S


title: Clinical efficacy and biomarker analysis of dual PD-1/CTLA-4 blockade in recurrent/metastatic EBV-associated nasopharyngeal carcinoma

status: Public on Apr 13 2023

city: Singapore

first: Narayanan

middle: Gopalakrishna

last: Iyer

address: 11 Hospital Cres

country: Singapore

institute: National Cancer Centre Singapore

summary: In this single arm non-randomized phase II trial, 40 patients with recurrent/metastatic EBV-positive nasopharyngeal carcinoma who failed prior chemotherapy received nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks. The best overall objective response rate was 38% with a median progression-free and overall survival of 5.3 and 19.5 months, respectively.  This regimen was well-tolerated and treatment-related adverse events requiring discontinuation were low. There was no correlation of response with PD-L1 expression or tumor mutation burden, however patients with low plasma circulating EBV-DNA titre (<7,800 IU/ml) showed a trend to better response and progression-free survival. Deep immunophenotyping of pre- and on-treatment tumor biopsies demonstrated early activation of the adaptive immune response, with T-cell cytotoxicity seen in responders prior to any clinically evident response. Profiling immune-subpopulations also identified a specific PD-1 and CTLA-4 expressing CD8 subpopulation that predicted for response to combined immune checkpoint blockade in nasopharyngeal carcinoma.

overall_design: RNA was extracted from 22 pre-treatment and 19 on-treatment tissue biopsies (19 patient-paired samples) and profiled using Nanostring PanCancer IO 360 Gene Expression Panel using nCounter MAX Analysis System. Data for all 41 samples are provided.

middle: G

first: Darren

middle: W

last: Lim


title: Sinus venosus adaptation models prolonged cardiovascular disease and reveals insights into evolutionary transitions of the vertebrate heart

city: Cincinnati

first: Nathan

last: Salomonis

state: OH

address: 3333 Burnet Avenue

department: Biomedical Informatics

institute: Cincinnati Children's Hospital

summary: How two-chambered hearts in basal vertebrates have evolved from single-chamber hearts found in ancestral chordates remains unclear. Here, we show that the teleost sinus venosus (SV) is a chamber-like vessel comprised of an outer layer of smooth muscle cells. We find that in adult zebrafish nr2f1a mutants, which lack atria, the SV comes to physically resemble the thicker bulbus arteriosus (BA) at the arterial pole of the heart through an adaptive, hypertensive response involving smooth muscle proliferation due to aberrant hemodynamic flow. Single cell transcriptomics show that smooth muscle and endothelial cell populations within the adapting SV also take on arterial signatures. Bulk transcriptomics of the blood sinuses flanking the tunicate heart reinforce a model of greater equivalency in ancestral chordate BA and SV precursors. Our data simultaneously reveal that secondary complications from congenital heart defects can develop in adult zebrafish similar to those in humans and that the foundation of equivalency between flanking auxiliary vessels may remain latent within basal vertebrate hearts.

overall_design: Single cell transcriptomic analysis of smooth muscle and endothelial cells within the adapting sinus venosus of nr2f1a mutants of the bulbus arteriosus and sinus venosus.

first: Jacob

middle: T

last: Gafranek

first: Padmapriyadarshini

last: Ravisankar

first: Enrico

last: D’Aniello

first: Kairavee

last: Thakkar

first: Ronald

last: Vagnozzi

first: Hee-Woong

first: Joshua

last: Waxman


title: LAPTM4B-YAP loop feedback amplification enhances the stemness of hepatocellular carcinoma

status: Public on Apr 11 2023

city: Fuzhou

first: Jianping

last: Liao

state: Fujian

address: 88 Jiaotong Road, Fuzhou, Fujian

institute: Fujian medical university

summary: To investigate the  function of LAPTM4B in the regulation of stemness, we established CD133+  HepG2 cells with or without knocked down LAPTM4B.

overall_design: We then performed gene expression profiling analysis using data obtained from RNA-seq of CD133+  HepG2 cells with or without knocked down LAPTM4B.

first: Jiahong

last: Wang

first: Yu

last: Xu

first: Yong

last: Wu

first: Meifeng

first: Qiudong

last: Zhao

first: Xiaodan

last: Tan

first: Yan

last: Meng

first: Lixin

last: Wei

first: Aimin

last: Huang


title: Transcriptomic profiling of liver tissues of 83 days fetuses in response to early maternal nutrient supplementation

city: Auburn

first: Wellison

middle: J. S.

last: Diniz

state: Alabama

address: CASIC Building 559 Devall Drive Auburn University, 205

department: Animal Sciences

institute: Auburn University

summary: We measured the gene expression profile of fetal liver to identify differentially expressed genes (DEG), biological processes (BP), and pathways underlying hepatic function and development in response to vitamin and mineral supplementation (VTM or NoVTM – at least 71 days pre-breeding to day 83 of gestation) and rate of weight gain (low [LG] or moderate [MG] – from breeding to day 83).   The treatments were arranged as follows: (1) no vitamin and mineral supplementation and low gain (NoVTM_LG, n = 8); (2) vitamin and mineral supplementation and low gain (VTM_LG, n = 8); (3) no vitamin and mineral supplementation and moderate gain (NoVTM_MG, n = 8), and (4) vitamin and mineral supplementation and moderate gain (VTM_MG, n = 7). Crossbred Angus beef heifers (n = 35) were randomly assigned to 1 of 4 treatments in a 2 × 2 factorial design. Fetal liver was collected on day 83 ± 0.27 of gestation snap-frozen, and stored at −80 °C. After RNA quality control, read mapping was performed with STAR aligner to the bovine ARS-UCD1.2 reference genome. Strand-specific RNA libraries were prepared using the NEBNext® Ultra™ II Directional RNA Library Prep Kit for Illumina (New England BioLabs®, Ipswich, MA, USA). Total RNA was extracted and libraries were sequenced on the Illumina® NovaSeq 6000 platform. After RNA quality control, read mapping was performed with STAR aligner to the bovine ARS-UCD1.2 reference genome. After quality control, differential gene expression analysis was carried out using edgeR. Differentially expressed genes (DEGs) were identified after multiple testing correction of the p-values based on the Benjamini-Hochberg methodology (FDR < 0.1). Our results show that vitamin and mineral supplementation and the rate of weight gain led to differential expression of hepatic genes in all treatments. We identified 591 unique differentially expressed genes across all six VTM-gain contrasts (FDR < 0.1). Over-represented pathways were related to energy metabolism, including PPAR and PI3K-Akt signaling pathways, as well as lipid metabolism, mineral transport, and amino acid transport. Our findings suggest that periconceptual maternal nutrition affects fetal hepatic function through altered expression of energy and lipid-related genes.

overall_design: Angus-cross heifers (n = 35) were randomly assigned by initial body weight (average = 359.5 ± 7.1 kg) to a 2×2 factorial arrangement of treatments. The factors examined included vitamin and mineral supplementation (VTM or NoVTM) and rate of gain (low gain – LG or moderate gain – MG). The treatments were arranged as follows: (1) no vitamin and mineral supplementation and low gain (NoVTM_LG, n = 8); (2) vitamin and mineral supplementation and low gain (VTM_LG, n = 8); (3) no vitamin and mineral supplementation and moderate gain (NoVTM_MG, n = 8), and (4) vitamin and mineral supplementation and moderate gain (VTM_MG, n = 7).  Diets were delivered once daily via total mixed ration and consisted of triticale hay, corn silage, modified distillers grains plus solubles, ground corn, and if indicated by treatment, mineral premix. To achieve MG (0.79 kg/d), heifers were fed the total mixed ration with the addition of the starch-based protein/energy supplement (a blend of ground corn, dried distillers grains plus solubles, wheat midds, fish oil, urea, and ethoxyquin). The LG heifers were maintained on the basal total mixed ration and targeted to gain 0.28 kg/d. The VTM treatment started 71 to 148 days before artificial insemination by providing 0.45 kg/heifer daily of a ground corn and vitamin and mineral premix (Purina Wind & Rain Storm All-Season 7.5 Complete, Land O’Lakes, Inc., Arden Hills, MN). Based on the VTM starting date, heifers were assigned to one of seven breeding groups so that the supplementation period was at least 60 days for all. At breeding, heifers were randomly assigned to either LG or MG treatments within their respective VTM treatment. Heifers were bred by artificial insemination using female-sexed semen from a single sire. The VTM and rate of gain treatments were carried out until day 83 ± 0.27 of gestation, when fetal tissues were collected. After QC, 31 samples (seven or eight samples per group) remained for further analyses. Differential gene expression analysis was carried out using edgeR. To make all pair-wise comparisons between the four treatment groups, six contrasts were created as follows: (1) VTM_MG vs. NoVTM_LG, (2) VTM_MG vs. VTM_LG, (3) VTM_MG vs. NoVTM_MG, (4) VTM_LG vs. NoVTM_LG, (5) VTM_LG vs. NoVTM_MG, (6) NoVTM_MG vs. NoVTM_LG. Multiple testing adjustment of the p-values (padj) was adopted using the Benjamini–Hochberg procedure for false discovery rate (FDR).

first: Carl

middle: R

last: Dahlen


title: RNA Polymerase II transcription independent of TBP

first: Sheila

last: Teves

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

overall_design: Refer to individual Series


title: G0S2 promotes antiestrogenic and pro-migratory responses in ER+ and ER- breast cancer cells.

city: Urbana

first: Michael

last: Spinella

state: IL

address: 2001 S Lincoln Ave

department: Comparative Biosciences

institute: University of Illinois at Urbana-Champaign

summary: G0/G1 switch gene 2 (G0S2) is known to inhibit lipolysis through inhibition of adipose triglyceride lipase (ATGL). Although G0S2 has also been proposed to be involved in cancer progression, this role appears complex, and mechanisms are unclear. We recently reported a role for G0S2 in ER+ breast cancer suppression as low G0S2 expression correlated with increased recurrence after antiestrogen therapy and increased G0S2 expression sensitized ER+ breast cancer cells to tamoxifen and PI3K/mTOR inhibitors. In this report we dissect the role of G0S2 in ER+ versus ER- breast cancer. Overexpression of G0S2 in ER- breast cancer cells increased cell proliferation while G0S2 overexpression in ER+ breast cancer cells decreased cell proliferation. Transcriptome analysis revealed that G0S2 mediated distinct but overlapping transcriptional responses in ER- and ER+ cells. G0S2 reduced genes associated with an epithelial phenotype, especially in ER- cells, including CDH1, ELF3, STEAP4 and TACSTD2 suggesting promotion of the epithelial-mesenchymal transition (EMT). G0S2 also repressed estrogen signaling and estrogen receptor target gene signatures, especially in ER+ cells, including TFF1 and TFF3. In addition, G0S2 overexpression increased cell migration in ER- cells and increased estrogen deprivation sensitivity in ER+ cells. Interestingly, two genes downstream of ATGL in fat utilization, HMGCS1 and HMGCS2, that are also rate-limiting in steroid hormone biosynthesis, were downregulated in G0S2 overexpressing ER+ cells. In addition, HSD17B11, a gene that converts estradiol to its less estrogenic derivative, estrone, was highly upregulated in G0S2 overexpressing ER+ cells, suggesting G0S2 overexpression has a negative effect of estradiol production and maintenance. High levels of estrone were confirmed to be present in G0S2 overexpressing cells. High expression of G0S2 and HSD17B11 was associated with improved relapse free survival in breast cancer patients while high expression of HMGSC1 was associated with poor survival. In addition, the expression of G0S2 positively and negatively correlated respectively, with expression of HSD17B11 and HMGSC1 in patient samples. Finally, we deleted G0S2 in breast cancer prone MMTV-PyMT mice that have been hypothesized to be partially estrogen sensitive during early stages of tumorigenesis but develop ER- tumors. In this context, G0S2 functioned as a tumor promoter, with G0S2 null mice demonstrating a slight increase in tumor latency and decrease in tumor weight and a larger inhibitory effect on tumor metastasis. Our data indicates a complex role for G0S2 in breast cancer, dependent on ER status, that may be mediated in part by suppression of the estrogen signaling pathway.

overall_design: gene expression of parental and Aza resistant cell lines in biological triplicate were analysed

first: Zeeshan

last: Fazal


title: Mast cells link immune sensing to antigen avoidance behavior [intestine]

city: Heidelberg

first: Robin

last: Thiele

address: Im Neuenheimer Feld 280

department: Immunology

institute: German Cancer Research Center

summary:
We investigated antigen-specific avoidance behavior in mice, and found that is critically dependent on mast cells.
We analyzed gene expression comparing naive versus immunized wild type mice, and versus mast cell-deficient mice at different times following antigen exposure

overall_design: Comparative gene expression profiling analysis of RNA-seq data for Cpa3+/+ (wild type) and Cpa3Cre/+ (mast cell-deficient) mice

first: Thomas

last: Plum

first: Rebecca

last: Binzberger

first: Fuwei

last: Shang

first: Daniel

last: Postrach

first: Candice

last: Fung

first: Marina

last: Fortea

first: Nathalie

last: Stakenborg

first: Zheng

first: Anke

last: Tappe-Theodor

first: Tanja

last: Poth

first: Duncan

last: MacLaren

first: Guy

last: Boeckxstaens

first: Rohini

last: Kuner

first: Claudia

last: Pitzer

first: Hannah

last: Monyer

first: Cuiyan

last: Xin

first: Joseph

middle: V

last: Bonventre

first: Satoshi

last: Tanaka

first: David

last: Voehringer

first: Pieter

last: Vanden Berghe

first: Jessica

last: Strid

first: Thorsten

last: Feyerabend

first: Hans-Reimer

last: Rodewald


title: Mast cells link immune sensing to antigen avoidance behavior

first: Robin

last: Thiele

summary:
We investigated antigen-specific avoidance behavior in mice, and found that is critically dependent on mast cells.
We analyzed gene expression comparing naive versus immunized wild type mice, and versus mast cell-deficient mice at different times following antigen exposure.
This SuperSeries is composed of the SubSeries listed below.


title: Breast metastatic tumors in lung can be substituted by lung-derived tumorsBreast metastatic tumors in lung can be substituted by lung-derived tumors

city: Jiaxing

first: Wu

last: Zhou

address: No 118, Rd Jiahang Avenue

institute: Jiaxing University

summary: Metastasis accounts for most cancer-associated deaths; yet, this complex process remains poorly understood, particularly the relationship between distant metastasis and primary site-derived cells. Here, we modified the classical MMTV-PyMT breast carcinoma model to trace the fate of mammary-derived carcinoma cells. We show that within the lung, when the metastatic breast carcinoma cells are conditionally depleted, transformed lung epithelial cells generate new metastases. Metastatic breast carcinoma cells transmit H19 long non-coding (lnc) RNA to lung epithelial cells through exosomes. SF3B1 bearing mutations at arginine-625 alternatively splices H19 lncRNA in lung epithelial cells, which selectively acts like a molecular sponge to sequester let-7a and induces Myc up-regulation. Under the conditional elimination of primary site-derived breast carcinoma cells, lung malignant cells expressing the mutated SF3B1 splice variant dominate the newly created tumors. Our study suggests that these new carcinoma cells originating from within the colonized organ can replace the primary site-derived malignant cells whenever their expansion is abrogated using an inducible diphtheria toxin receptor in our designed system. These findings should call for a better understanding of metastatic tumors with the specific origin during cancer metastasis.

overall_design: To identify the origin of these infiltrating cells, we performed Single-cell RNA-Seq on the lung metastasis infiltrating cells and cells isolated from peritumoral tissue of lung metastasis of 16 weeks old MPG mice.

first: Jin

last: Xu

first: Jun

last: Cao

last: Xia

first: Ying

last: Zhu

first: Yi

middle: H

last: Lin

first: Lei

first: Ming

first: Bing

middle: M

last: Fang


title: STAT5 tetramerization is a central determinant of monocyte fate and colonic pathogenicity

city: Morgantown

first: Gangqing

last: Hu

state: West Virginia

address: 64 Medical Center Drive

department: MicroBiology, Immunology, and Cell Biology

institute: West Virginia University

summary: In response to external stimuli during immune responses, monocytes can have multifaceted roles such as pathogen clearance and tissue repair. However, aberrant control of monocyte activation can result in chronic inflammation and subsequent tissue damage. Granulocyte-macrophage colony-stimulating factor (GM-CSF) induces monocyte differentiation into a heterogenous population of monocyte-derived dendritic cells (moDCs) and macrophages. However, the downstream molecular signals that dictate the differentiation of monocytes under pathological conditions is incompletely understood. We report here that the GM-CSF-induced STAT5 tetramerization is a critical determinate of monocyte fate and function. Monocytes require STAT5 tetramers to differentiate into moDCs, whereas STAT5 tetramer deficiency yields a macrophage phenotype. In the dextran sulfate sodium model of colitis, STAT5 tetramer-deficient monocytes exacerbate disease severity. Mechanistically, GM-CSF signaling in STAT5 tetramer-deficient monocytes results in the overexpression arginase I and a reduction in nitric oxide synthesis following stimulation with lipopolysaccharide. Correspondingly, the inhibition of arginase I activity and supplementation with a sustained concentration of nitric oxide ameliorates the worsened colitis in STAT5 tetramer-deficient mice. Thus, this study suggests a protective role of STAT5 tetramers in inflammatory bowel disease through the regulation of arginine metabolism. We previously reported that STAT5 tetramerization in monocytes is detrimental in autoimmune-mediated neuroinflammation. This study highlights the opposing role of STAT5 tetramers in inflammatory bowel disease.

overall_design: Ly6C+ CCR2+ monocytes were enriched from the bone marrow of WT and STAT5 tetramer-deficient (DKI) mice using monocyte isolation kit (Miltenyi Biotec), then left untreated (day 0) or stimulated with 20 ng/ml GM-CSF for 3 and 6 days. 3-independent experiments were performed.

first: Kelly

last: Monaghan

first: Wen

last: Zheng

first: Halima

last: Akhter

last: Wang

first: Amanda

last: Ammer

first: Peng

last: Li

first: Jian-Xin

first: Warren

middle: J

last: Leonard

first: Edwin

last: Wan


title: Mast cells link immune sensing to antigen avoidance behavior [stomach]

first: Robin

last: Thiele

first: Thomas

last: Plum

first: Rebecca

last: Binzberger

first: Fuwei

last: Shang

first: Daniel

last: Postrach

first: Candice

last: Fung

first: Marina

last: Fortea

first: Nathalie

last: Stakenborg

first: Zheng

first: Anke

last: Tappe-Theodor

first: Tanja

last: Poth

first: Duncan

last: MacLaren

first: Guy

last: Boeckxstaens

first: Rohini

last: Kuner

first: Claudia

last: Pitzer

first: Hannah

last: Monyer

first: Cuiyan

last: Xin

first: Joseph

last: Bonventre

first: Satoshi

last: Tanaka

first: David

last: Voehringer

first: Pieter

last: Vanden Berghe

first: Jessica

last: Strid

first: Thorsten

middle: B

last: Feyerabend

first: Hans-Reimer

last: Rodewald


title: Discrimination between Pre- and Post-capillary Pulmonary Hypertension using Platelet RNA

status: Public on Apr 10 2023

city: Amsterdam

first: Myron

last: Best

address: De Boelelaan 1117

department: Neurosurgery

country: Netherlands

institute: VU University Medical Center

summary: We report RNA-sequencing data of 100 blood platelet samples collected from patients with pulmonary hypertension with pre-capillary origin (n=50) and post-capillary origin (n=50)

overall_design: Blood platelets were isolated from whole blood in purple-cap BD Vacutainers containing EDTA anti-coagulant by standard centrifugation. Total RNA was extracted from the platelet pellet, subjected to cDNA synthesis and SMARTer amplification, fragmented by Covaris shearing, and prepared for sequencing using the Truseq Nano DNA Sample Preparation Kit. Subsequently, pooled sample libraries were sequenced on the Illumina Hiseq 2500 or 4000 platform. All steps were quality-controlled using Bioanalyzer 2100 with RNA 6000 Picochip, DNA 7500 and DNA High Sensitivity chips measurements. For further downstream analyses, reads were quality-controlled using Trimmomatic, mapped to the humane reference genome using STAR, and intron-spanning reads were summarized using HTseq.

first: Mohammad

last: Arkani


title: Lining macrophages initiate articular inflammation

city: Oxford

first: Irina

last: Udalova

address: Roosevelt Drive

department: Kennedy Institute of Rheumatology

institute: University of Oxford

summary: This dataset contains the transcriptional analysis of lining macrophages and sub-lining macrophages from vehicle or antigen-induced arthritis(AIA) mouse model.

overall_design: mice were immunized by two subcutaneous injection of 20 µg mBSA (40 mg/ml) emulsified with CFA (3.3 mg/ml) and PBS to a final 100 µl volume per mouse. Two hundred lining and sublining macrophages from 3 WT and 3 IRF5KO mice, isolated from PBS-Mbsa injected knees. Sorting of synovial macrophages was carried out from the knee cell suspensions. Lining macrophages were defined as CD45+, Linage- (NK1.1, CD3, CD19), CD11b+, F4/80+ and VSIG4+ cells, whereas sublining macrophages were CD45+,  Lin-, CD11b+, F4/80+ and VSIG4-.

first: Kristina

last: Zec

first: Barbora

last: Schonfeldova

first: Zhichao

last: Ai

first: Erinke

last: Van Grinsven

first: Gabriela

last: Pirgova

first: Hayley

middle: L

last: Eames

first: Dorothee

last: Berthold

first: Moustafa

last: Attar

first: Ewoud

last: Compeer

first: Tal

middle: I

last: Arnon


title: Comprehensive the effect of ZNRF1 on TLR3 activation in bone marrow-derived macrophages upon poly(I:C) stimulation

city: Taipei

first: You-Sheng

last: Lin

state: Not US or Canada

address: No.7.Chung San South Road, Taipei 10002( Institute of Molecular Medicine, College of Medicine, National Taiwan University)

country: Taiwan

summary:
To evaluate comprehensively the effect of ZNRF1 on TLR3 activation, we stimulated WT or Znrf1 knockout BMDM with poly(I:C) for 4 hours.
We then performed gene expression profiling analysis using data obtained from RNA-seq of  duplicate samples.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for WT  and Znrf1 knockout BMDMs upon poly(I:C) stimulation for 4 hours.


title: Transcriptional remodeling of primary human monocytes trained with interleukin-4 (IL4)

status: Public on Apr 06 2023

city: Parkville

first: Boris

last: Novakovic

state: Victoria

address: Murdoch Children's Research Institute, Royal Children's Hospital, Flemington Road

country: Australia

institute: Murdoch Children's Research Institute

summary: Trained immunity is a phenomenon whereby innate immune cells such as monocytes or macrophages undergo functional reprogramming after exposure to certain microbial components, altering their responses to future exposures. This study profiled the transcriptome of human macrophages trained with IL4 and then re-exposed to lipopolysaccharide.

overall_design: Human primary monocytes were isolated using Ficoll and Percoll gradient separation. Baseline monocytes were collected after 1 hour in culture (attached). Samples for media only, LPS only, IL4, or IL4+LPS exposures were collected at 4 hours post stimulation. Additionally, monocytes were exposed to media alone, LPS, IL4 and IL4+LPS for 24 hours, allowed to differentiate to macrophages for 5 days and then re-exposed to LPS for 4 hours.

first: Rutger

last: Roring

first: David

last: Schrijver

first: Mihai

last: Netea

first: Willem

last: Mulder


title: Charting a high-resolution roadmap for regeneration of pancreatic β cells by in vivo transdifferentiation from adult acinar cells

city: Shanghai

first: Xiangyi

last: Chen

address: No. 1239, Siping Road, Shanghai, China

institute: Weida Li

summary: The process of regeneration by in vivo transdifferentiation in mammals is poorly understood. Here, using pancreatic β cell regeneration as a paradigm, we performed a single-cell transcriptomic study of in vivo transdifferentiation from adult mouse acinar cells to induced β cells.

overall_design: Adenovirus (Pdx1, Mafa, Ngn3 co-expression vector, Ad-M3C) infected pancreatic cells are labeled by red fluorescent protein mCherry, and mCherry+ Calcein Blue, AM+ cells are sorted by FACS for scRNA-seq library construction. Acinar cells labeled with Calcein Blue, AM from no treat mice are also sorted by FACS to construct scRNA-seq library for control.

first: Gang

last: Liu

first: Yana

last: Li

first: Mushan

first: Sheng

first: Qing

last: He

first: Shuxin

first: Qiang

last: Su

first: Minglu

last: Xu

first: Zhenning

last: Zhang

first: Zhen

last: Shao

first: Weida


title: Targeted transcriptome analysis of isolated intestinal epithelial cells from mice with constitutive Ptpn2-deficiency

city: RIVERSIDE

first: Declan

last: McCole

state: CA

address: 3401 Watkins Drive

department: Biomedical Sciences

institute: University of California Riverside

summary:
Background & aims: Loss-of-function variants in the PTPN2 gene are associated with increased risk of inflammatory bowel disease. We recently showed that Ptpn2 is critical for intestinal epithelial cell (IEC) barrier maintenance, IEC-macrophage communication, and modulation of the gut microbiome in mice, restricting expansion of a small intestinal pathobiont associated with inflammatory bowel disease. Here, we aimed to identify how Ptpn2 loss affects ileal IEC subtypes and their function in vivo.

Methods: Constitutive Ptpn2 wild-type, heterozygous, and knockout (KO) mice, as well as mice with inducible deletion of Ptpn2 in IECs, were used in the study. Investigation was performed using imaging techniques, flow cytometry, enteroid culture, and analysis of gene and protein levels of IEC markers.

Results: Partial transcriptome analysis showed that expression of Paneth cell-associated antimicrobial peptides Lyz1, Pla2g2a, and Defa6 was down-regulated markedly in Ptpn2-KO mice compared with wild-type and heterozygous. In parallel, Paneth cell numbers were reduced, their endoplasmic reticulum architecture was disrupted, and the endoplasmic reticulum stress protein, C/EBP-homologous protein (CHOP), was increased in Ptpn2-KO mice. Despite reduced Paneth cell number, flow cytometry showed increased expression of the Paneth cell-stimulatory cytokines interleukin 22 and interferon γ+ in CD4+ T cells isolated from Ptpn2-KO ileum. Key findings in constitutive Ptpn2-KO mice were confirmed in epithelium-specific Ptpn2ΔIEC mice, which also showed impaired lysozyme protein levels in Paneth cells compared with Ptpn2fl/fl control mice.

Conclusions: Constitutive Ptpn2 deficiency affects Paneth cell viability and compromises Paneth cell-specific antimicrobial peptide production. The observed effects may contribute to the increased susceptibility to intestinal infection and dysbiosis in these mice.

overall_design: Intestinal epithelial cells were isolated from 21 days old mice (littermates) as Ptpn2-KO mice are normal at birth but die within 3-5 weeks of age. Total RNA was used. Results of two separate panels with a predefined set of targets ('AutoImmune Profiling’ and ‘PanCancer Pathways') from the same intestinal segment were combined for analysis, with the addition of 30 customized targets to each panel comprising of IEC markers, function and differentiation factors, host-bacteria interaction, autophagy, immune response and iron transport, totaling >1500 targets. Data from each panel was normalized separately and then consolidated using the MultiRLF function in the nSolver Analysis Software 4.0.


title: RNA-seq analysis of CncC (Nrf2) over-expression to induce the loser status in Drosophila wing discs

city: Bristol

first: Eugenia

last: Piddini

address: Biomedical Sciences Building, University walk

department: CMM

institute: University of Bristol

summary: To investigate the mechanisms of cell competition, we analysed the molecular differences between wild type and mild CncC (Nrf2) over-expressing causing the loser phenotype in Drosophila wing discs. We then compared the genes differentially expressed in these conditions to our previously identified ‘loser signature’ which reveal a significant overlap. From this later comparison, we raised a list of 121 up-regulated genes to conduct a cell competition screen using PECAn (Pipeline for Enhanced Clonal Analysis) for automating analysis of mosaic experiment.

overall_design: Analysis of RNA-seq profiles from wild type and CncC (Nrf2) over-expressing Drosophila wing discs, each condition in triplicates.

first: Iwo

last: Kucinski


title: The landscape of circular RNAs in neuroblastoma

city: Berlin

first: Steffen

last: Fuchs

address: Augustenburger Platz 1

department: Pediatric Oncology

institute: Charité - Universitätsmedizin Berlin


title: Carboplatin resistance-associated changes in the 3D chromatin landscape of a triple-negative breast cancer Patient-Derived Xenograft [Hi-C]

city: Richmond

first: Mikhail

last: Dozmorov

state: VA

address: 830 E Main St

department: Biostatistics

institute: Virginia Commonwealth University

summary: Changes in the three-dimensional (3D) structure of the genome are an emerging hallmark of cancer. However, little is known about the rewiring of the 3D chromatin landscape during cancer progression to a chemotherapy-resistant state. We utilized a patient-derived xenograft (PDX) mouse model of triple-negative breast cancer (UCD52) to characterize changes in the 3D structure between the primary tumor and carboplatin-resistant state. Systematic integration of matched chromatin conformation capture (Hi-C), RNA-seq, and whole-genome sequencing data revealed a widespread increase in short-range (<2Mb) interactions with the corresponding increase in chromatin looping and topologically associating domain (TAD) formation, chromatin state switching into a more active state, large-scale deletions, amplification of ATP-binding cassette (ABC) transporters and nearly complete shutdown of drug metabolism pathways. Rewiring of the 3D genome was associated with TP53, TP63, BATF, FOS-JUN family of transcription factors and led to activation of many aggressiveness-, metastasis- and other cancer-related pathways. Transcriptome changes suggest the role of downregulated protein-coding genes and upregulated long-noncoding RNAs in drug resistance. Integrative analysis confirmed increased ribosome biogenesis and oxidative phosphorylation, suggesting the role of mitochondrial metabolic processes. Our results highlight that 3D genome remodeling may be a key mechanism underlying drug resistance.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Hi-C sequencing analysis performed on two replicates for each of the two phenotypes (primary tumor and carboplatin-resistant state).

first: Maggie

last: Marshall

first: Narmeen

last: Rashid

first: Jacqueline

last: Grible

first: Amy

last: Olex

first: Kavita

last: Murthy

first: Abhijit

last: Chakraborty

first: Joaquin

last: Reyna

first: Daniela

last: Salgado Figueroa

first: Erika

last: Da-Inn Lee

first: Brittany

last: Baur

first: Sushmita

last: Roy

first: Ferhat

last: Ay

first: Chuck

last: Harrell


title: Ehmt2’s transcriptional coactivation restricts glucocorticoid-induced insulin resistance in a study with male mice

status: Public on Apr 07 2023

city: Berkeley

first: Jen-Chywan

last: Wang

address: 315 Morgan Hall, UC Berkeley

department: Nutritional Sciences & Toxicology

institute: UC Berkeley

summary: Glucocorticoids play a key role in metabolic adaptation during stress, such as fasting and starvation. Excess and/or chronic glucocorticoid exposure, however, causes metabolic disorders that include insulin resistance dyslipidemia and hepatic steatosis. Glucocorticoid receptor (GR) is known to regulate a wide variety of primary target genes. However, the specificity of this regulation due to interactions with various transcriptional coactivators such as Ehmt2 remains to be further investigated. Here, we aim to identify Ehmt2 coactivation function-dependent GR primary target genes that may play a role in promoting insulin sensitivity

overall_design: WT C57BL6/J male mice from Jackson laboratory were purchased as controls. Ehmt2 mutant mice (Ehmt2K182R/K182R) were generated, in which nucleotide sequences encoding lysine 182 were converted from AAA to AGG (arginine), using CRISPR knock in technology. 8 week old male mice were treated for 5 hours with 2mg/kg dexamethasone sodium phosphate (Sigma, Cleveland, OH, PHR1768)via IP injection. Livers were collected and RNA was extracted.

first: Rebecca

last: Lee

first: Ariel

last: Tsay

first: Danielle

last: Li

last: Chang

first: Nicholas

last: Yiv

first: Coralie

last: Poulard

first: Sharon

last: Tian

first: Michael

last: Stallcup

first: Miles

last: Pufall


title: Carboplatin resistance-associated changes in the 3D chromatin landscape of a triple-negative breast cancer Patient-Derived Xenograft [RNA-Seq]

first: Mikhail

last: Dozmorov

overall_design: RNA-sequencing analysis performed on three replicates for each of the two phenotypes (primary tumor and carboplatin-resistant state).

first: Maggie

last: Marshall

first: Narmeen

last: Rashid

first: Jacqueline

last: Grible

first: Amy

last: Olex

first: Kavita

last: Murthy

first: Abhijit

last: Chakraborty

last: Reyna


title: Carboplatin resistance-associated changes in the 3D chromatin landscape of a triple-negative breast cancer Patient-Derived Xenograft

status: Public on Apr 05 2023


title: The hepatic immunological pattern shaped by dominant-subdominant cellular relationship creates a collective function beyond the function of each cellular constituent to orchestrate the progression of hepatocellular carcinoma

status: Public on Apr 04 2023

last: Koelsch

state: Virginia

address: 1810 East Cary Street Apt MG02

department: Microbiology & Immunology

summary: Abundance of data on the role of inflammatory immune responses in the progression or inhibition of hepatocellular carcinoma (HCC) has failed to offer a curative immunotherapy for HCC. This is largely because of taking reductionist approaches and missing the collective function of the hepatic immune system by focusing on specific immune cell type. To discover the collective immune function, we take systems immunology approach by performing high-throughput analysis of snRNAseq data collected from the liver of DIAMOND mice during the progression of nonalcoholic fatty liver disease (NAFLD) to HCC. We report that mutual signaling interactions of the hepatic immune cells in a dominant-subdominant manner, as well as their interaction with structural cells shape the immunological pattern manifesting a collective function beyond the function of the cellular constituents. Within different immune pattern, the same cytokines manifest different functional signaling pathways. These data suggest that discovery of the immune pattern not only explains dynamic changes in immune cells during the course of diseases but also offers immune modulatory approaches for the treatment of NAFLD and HCC.

overall_design: Six DIAMOND mice (129A1/SvIm and C57BL/6J cross mice) were stratified into experimental groups receiving different diets at two months of age. Two mice (n=2) were included in the control group (fed a standard chow diet (CD) for 40 weeks), two were in the Pre-T group (prior to tumor development; fed a high-fat diet with sugar water for 40 weeks), and the last two in the Post-T group (after tumor development due to being on high-fat diet with sugar water for 48 weeks) to recapitulate the changes seen during the progression of non-alcoholic fatty liver disease (NAFLD) to hepatocellular carcinoma (HCC).

first: Masoud

last: Manjili

first: Arun

last: Sanyal

first: Hussein

middle: F

last: Aqbi

first: Faridoddin

last: Mirshahi

first: Mulugeta

last: Saneshaw

middle: O

last: Idowu


title: Mature primary human osteocytes in mini organotypic cultures secrete FGF23 and PTH1-34-regulated sclerostin

status: Public on Apr 03 2023

first: Philippa

last: Hulley

address: Windmill Road

department: NDORMS

summary: Osteoblasts from 4 donors were seeded onto 20 constructs. Constructs were constructed as described: Calcium phosphate (brushite / β-TCP) posts were pinned into a Sylgard 184 silicone elastomer (base and curing agent, Dow Corning Corporation) base layer in 6-well dishes. Cells were seeded in fibrinogen onto a thrombin gel and subsequently cultured in 3ml of proliferation media (osteoblast media, 50 μg/ml ascorbate-2-phosphate, 40 μg/ml proline) per well until cells had fully contracted the gel between the support posts. Week 0 constructs were harvested and snap-frozen at this point with the remainder transferred to osteogenic media (proliferation media, 10 mM β-glycerophosphate, 10 nM dexamethasone) and harvested at 2, 4, 6 and 8 weeks.

overall_design: RNA expression profiling during differentiation of human primary osteoblasts to osteocytes in mini organotypic cultures. RNA extracted from the onset of contruction (Time 0) and at the onset of ossification (8 weeks) and at 2 week intervals in between, from four different donors.

first: Helen

last: Knowles

first: Anastasios

last: Chanalaris

first: Argyro

last: Koutsikouni

first: Adam

middle: P

last: Cribbs

first: Liam

last: Grover

middle: A


title: Transcriptome analysis in tumor budding positive hepatocellular carcinoma tissue samples relative to tumor budding negative hepatocellular carcinoma tissue samples

status: Public on Apr 02 2023

city: Jinan

first: Shaoshao

last: Xu

state: Shandong

address: 44 Wenhua Xi Road

department: Cheeloo College of Medicine

institute: shandong university

summary:
Tumor budding (TB) has become a crucial factor for predicting the malignancy grade and prognostic outcome for multiple solid cancers.Studies have investigated the prognostic value of TB within hepatocellular carcinoma (HCC). However, its molecular mechanism within HCC remains unclear. This is the first study to discover and compare the expression of differentially expressed genes (DEGs) between TB-positive and TB-negative HCC tissues.
Total RNA was extracted from 40 fresh HCC tissue samples with different TB statuses and then sequenced. This study provides insights into the possible mechanisms of TB in HCC and revealed potential predictive diagnosis markers and treatment targets for HCC.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for TB-positive and TB-negative HCC tissue samples.

first: Di

last: Jiang

first: Chuanpeng

last: Zhang

first: Yanrong

last: Liu


title: Tilianin improves cognition in a vascular dementia rodent model by targeting miR-193b-3p/CaM- and miR-152-3p/CaMKIIα-mediated inflammatory and apoptotic pathways

city: Beijing

first: Ting

last: Sun

address: Tiantanxili No.1

institute: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College

summary: Although vascular dementia (VaD) is the second most prevalent form of dementia, there is currently a lack of effective treatments. Tilianin, isolated from the traditional drug Dracocephalum moldavica L., may protect against ischemic injury by inhibiting oxidative stress and inflammation via the CaMKII-related pathways but with weak affinity with the CaMKII molecule. microRNAs (miRNAs), functioning in post-transcriptional regulation of gene expression, may play a role in the pathological process of VaD via cognitive impairment, neuroinflammatory response, and neuronal dysfunction. This study aimed to investigate the role of tilianin in VaD therapy and the underlying mechanism through which tilianin regulates CaMKII signaling pathways based on miRNA-associated transcriptional action.

overall_design: Brains of rats with 2-vessel occlusion (2VO) and brains of rats with 2VO after treated with tilianin

first: Rui

first: Zhuorong

last: Li

first: Linjie

last: Tan

first: Mimin

first: Li

last: Zeng

first: Kaiyue

last: Zhao

first: Zhongdi

last: Cai

first: Shengnan


title: Single cell sequencing of mouse gammadelta T cells

status: Public on Apr 01 2023

city: Louisville

first: Jun

last: Yan

state: KY

address: 505 S Hancock Street

institute: University of Louisville

summary: Mouse gammadelta T cells were sorted from adult C57Bl/6 mouse spleen and lymph nodes and cells were subjected to scRNA-seq

overall_design: Single cell suspensions from pooled spleens and lymph nodes were stained with viability dye, CD45, CD3 and gdTCR. Cells were gated on viable, CD45+CD3+gdTCR+ cells.


title: In vitro, genomic context identification of transcription factor binding sites for bZIP C/S1 homodimers and heterodimers

city: New York

first: Shao-shan

middle: Carol

last: Huang

state: NY

address: 12 Waverly Pl

department: Biology

institute: New York University

summary: In eukaryotes, many transcription factors (TF) usually form dimers or oligomers with itself or other TFs to regulate gene expression. To study how homo- and heterodimerization of TFs affect DNA binding specificity, we developed a double DNA Affinity Purification sequencing (double DAP-seq; dDAP-seq) technique that maps heterodimer binding sites in endogenous genome context and applied it to elucidate the binding profiles of homo- and heterodimers of the Group C and S1 basic leucine zipper (bZIP) transcription factors in Arabidopsis. Genome-wide binding profiles of twenty pairs of bZIP C/S1 heterodimers and bZIP S1 homodimers revealed that heterodimerization significantly expands the DNA binding preferences of homodimers, creating unique binding sites and target gene functions. In addition to the classical ACGT elements recognized by plant bZIPs, we found the Group C/S1 dimers bind to sequence motifs that might share an origin with the yeast bZIP GCN4. Further analysis of heterodimer-specific binding sequences uncovered two types of motif recognition patterns that mediate heterodimer specificity. Our study shed light on the functions and mechanisms of TF dimerization and demonstrated the potential of dDAP-seq in deciphering the complexity of these interactions within or across TF families.

overall_design:
Identification of binding sites for  homodimers and heterodimers of bZIP transcription factors in Arabidopsis by direct sequencing of affinity purified genomic DNA fragments.
Please note that the processed data files generated from multiple/merged samples are indicated in the corresponding sample description field and are linked as Series supplemenatary files.

middle: C

first: Miaomiao


title: Transcription of C. albicans SC5314

city: RICHMOND

first: Jizhong

last: Han

state: VA - Virginia

address: 1220 E. Broad St.

summary: Effect of 2H on the transcription level of C. albicans

overall_design: 2H was added to a final concentration of 100 µM and the culture was grown at 37 °C for 30 minutes. A culture with addition of DMSO was used as a control. Each group repeat three times.

first: Qinglian

first: Cancan

first: Liqing

last: Hu


title: Investigate the roles of the N-terminal amino acid different between H3 and H3.3

city: Baltimore

first: Jennifer

last: Urban

state: MD

address: 3400 N. Charles Street

department: Biology Department

institute: Johns Hopkins University

summary: Adult stem cells undergo asymmetric cell divisions to produce two daughter cells with distinct cell fates: one capable of self-renewal and the other committed for differentiation. Mis-regulation of this delicate balance can lead to cancer and tissue degeneration. During asymmetric cell division of Drosophila male germline stem cells (GSCs), preexisting (old) and newly synthesized histone H3 are differentially segregated whereas old and new histone variant H3.3 are more equally inherited. However, what underlies these distinct inheritance patterns remains unknown. Here, we report that the N-terminal tails of H3 and H3.3 are critical for their histone inheritance patterns, as well as GSC maintenance and proper differentiation. H3 and H3.3 differ at the 31st position in their N-termini with Alanine for H3 and Serine for H3.3. By swapping these two amino acids, we generated two mutant histones (i.e., H3A31S and H3.3S31A) and expressed them in the early-stage germline. We identified over-population of early-stage germ cells in the H3A31S-expressing testes and significant germ cell loss in testes expressing the H3.3S31A. Asymmetric H3 inheritance is disrupted in the H3A31S-expressing GSCs, due to mis-incorporation of old histones between sister chromatids during DNA replication. Together, our findings indicate a critical role for the different amino acid composition of the N-terminal tails between H3 and H3.3 in an endogenous stem cell lineage, and provides insight into the importance of proper histone inheritance in specifying cell fates and regulating cellular differentiation.

overall_design: Antibody-guided MNase digestion was used to evaluate the localization and enrichment of wild type and mutant histones H3 and H3.3 in the Drosophila male germline. Cell-specific expression of histones was achieved by driving the expression of each GFP-tagged histone in the germline using the nanos promoter. Co-expression of a transgene containing the Unpaired gene resulted in germline and somatic stem cell tumors that provided sufficient material for this genomic study. For each histone type (H3, H3A31S, H3.3, and H3.3S31A), three biological replicates were performed each containing ~18-20 testes.

first: Chinmayi

last: Chandrasekhara

first: Rajesh

last: Ranjan

first: Wai

last: Ku

first: Johnathan

last: Snedeker

first: Keji

first: Xin

last: Chen


title: Protective Role of Macrophage Osteopontin in NASH

status: Public on Mar 31 2023

city: Chicago

first: Hui

last: HAN

address: 909 S Wolcott Ave

institute: University of Illinois at Chicago

summary: To study role of macrophage derived osteopontin in NASH

overall_design: RNA sequencing was performed in total liver and isolated liver resident macrophages from mice after 6 month feeding with control or NASH diet

first: Natalia

last: Nieto


title: Kinase-independent activity of DYRK1A promotes viral entry of highly pathogenic human coronaviruses

city: New Haven

first: Qin

email: qin.yan@yale.edu, craig.wilen@yale.edu

address: 310 Cedar St.

department: Pathology

institute: Yale University

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

overall_design: Refer to individual Series


title: Effects of CRABP1 overexpression on thyroid cancer cell lines

first: Shih-Ping

last: Cheng

address: 92, Chung-Shan North Road, Section 2

department: Department of Surgery

institute: MacKay Memorial Hospital

summary: Cellular retinoic acid-binding protein 1 (CRABP1) is a cytosolic lipid-binding protein which is thought to play an important role in regulating retinoic acid signaling. Loss of CRABP1 expression has been observed in thyroid cancer. We transfected a CRABP1-overexpressing vector to thyroid cancer cells to elucidate its oncogenic effects.

overall_design: Human thyroid cancer cell lines FTC-133 and 8505C were transfected with a CRABP1-overexpressing vector or an empty vector. Cellular RNA was then subjected to RNA sequencing.