title: PP2Ac/STRN4 negatively regulates STING-Type I interferon signaling in tumor associated macrophages [RNA-Seq]

summary: STING-Type I interferon (IFN) signaling in myeloid cells plays a critical role in effective antitumor immune responses, but STING agonist as monotherapy has shown limited efficacy in clinical trials. The mechanisms that downregulate STING signaling are not fully understood. Here, we report that Protein phosphatase 2A (PP2A) with its specific B regulatory subunit STRN4 negatively regulated STING-Type I IFN in macrophages. Mice with macrophages PP2A deficiency exhibited reduced tumor progression. The tumor microenvironment showed decreased immunosuppressive and increased IFN-activated macrophages and CD8+ T cells. Mechanistically, we demonstrated that hippo kinase MST1/2 was required for STING activation. STING agonist induced dissociation of PP2A from MST1/2 in normal macrophages, but not in tumor conditioned macrophages. Furthermore, our data showed that STRN4 mediated PP2A binding to and dephosphorylation of hippo kinase MST1/2, resulting in stabilization of YAP/TAZ to antagonize STING activation. In human GBM patients, YAP/TAZ was highly expressed in tumor-associated macrophages but not in non-tumor macrophages. We also demonstrated that PP2A/STRN4 deficiency in macrophages reduced YAP/TAZ expression and sensitized tumor conditioned macrophages to STING stimulation. In summary, we demonstrated that PP2A/STRN4-YAP/TAZ is a previously unappreciated mechanism that mediate immunosuppression in tumor-associated macrophages and targeting PP2A/STRN4-YAP/TAZ axis can sensitize tumors to immunotherapy.

overall_design: intergrative analysis of RNA-seq and scRNA upon PP2A KO.

first: Winson

last: Ho

first: Oishika

last: Das

first: Isha

last: Mondal

first: Rongze

last: Lu


title: mRNA transcriptomic changes during pre and postnatal muscle hypertrophy of the longissimus in sheep

status: Public on Feb 09 2023

city: Clemson

first: Susan

last: Duckett

state: South Carolina

address: 105 Collings ST, RM 112 BRC

department: Animal and Veterinary Science

country: USA

institute: Clemson University

type: Expression profiling by high throughput sequencing

summary: Longissimus muscle samples were collected from lambs at 4 developmental time points (prenatal  gestational d 85 and 133, and postnatal d 42 and 243). Muscle samples were examined to determine the impact of myofiber hypertrophy on the mRNA profile.

overall_design: This study is comprised of 12 samples, There are 4 developmental groups with 3 replicates each. Prenatal time gestational d 85  and 133. Postnatal time d 42 and 243.

first: Maslyn

middle: A

last: Greene

first: Rooksana

last: Noorai


title: The NFIA-ETO2 fusion blocks terminal erythroid maturation and induces pure erythroid leukemia (PEL) in cooperation with mutant TP53

city: Basel

first: Jonathan

last: Seguin

address: Spitalstrasse 33

country: Switzerland

institute: UKBB-DBM

summary:
The NFIA-ETO2 fusion is the product of a t(1;16)(p31;q24) chromosomal translocation so far exclusively found in pediatric patients with pure erythroid leukemia (PEL). To address its role for the pathogenesis of the pure erythroid leukemia, we retrovirally expressed the PEL-associated NFIA-ETO2 fusion or an in active NFIA-ETOdeltaNHR4 mutant in primary erythroblasts in fetal liver-derived erythroblasts from either wild-type (C57/B6) or TP53R248Q (HUPKI) mice.
Gene expression was determined by RNA sequencing from cells kept in maintenance medium (MM) or 24h in differentiation-inducing medium (DM)

overall_design: Comparative gene expression profiling analysis (RNA-seq) from primary erythroblasts expressing NFIA-ETO2 in wildtype or TP53R248Q (HUPKI) mice.

first: Maria-Riera

last: Piqué-Borràs

first: Frederik

last: Otzen Bagger

first: Robert

last: Ivanek

first: Juerg

last: Schwaller


title: Effect of NFIA-ETO2 gene fusion on MEL cells during proliferation and impaired erythroid differentiation.

summary:
The NFIA-ETO2 fusion is the product of a t(1;16)(p31;q24) chromosomal translocation so far exclusively found in pediatric patients with pure erythroid leukemia (PEL). To address its role for the pathogenesis of the pure erythroid leukemia, we retrovirally expressed the PEL-associated NFIA-ETO2 fusion in MEL cells.
Gene expression was determined by RNA sequencing from MEL cells which express or not NFIA-ETO2.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for MEL cells expressing NFIA-ETO2 or not (control)


title: PP2Ac/STRN4 negatively regulates STING-Type I interferon signaling in tumor associated macrophages [scRNA-seq]

city: Memphis

first: Beisi

last: Xu

state: Tennessee

address: 262 Danny Thomas Pl

department: Center for Applied Bioinformatics

institute: St Jude Children's Research Hosipital

overall_design: In this experiment, we studied the effect of myeloid PP2A KO on the immune landscape of subcutanous or intracranial glioma microenvironment. We implanted subcutanous or intracranial SB28 murine glioma in WT and LysMcrePP2Acfl/fl mice. 18 days after implantation, tumor tissue was harvested, and single cell suspensions were obtained and sent for sequencing.


title: mTORC1 upregulates B7-H3/CD276 to inhibit antitumor T cells and drive tumor immune evasion [RNA-seq]

status: Public on Feb 08 2023

city: Haining

first: Heng-Jia

last: Liu

state: Zhejiang

address: 718 East Haizhou Road

department: International Campus

country: China

institute: Zhejiang University - University of Edinburgh

summary: Immune checkpoints are often expressed on tumor cells; it remains a prevailing need to identify the mechanisms underlying their regulation and therapeutic benefit. The immune checkpoint molecule B7-H3 is upregulated in many human tumors, including those with high mechanistic/mammalian target of rapamycin complex (mTORC1) activity. Still, its role in tumor immunity and the impact of B7-H3-targeted therapy on the tumor immune microenvironment are largely uncharacterized in mTORC1-hyperactive tumors. Here, we used a syngeneic murine model of tuberous sclerosis complex (TSC), a model of mTORC1 hyperactivity, to assess the mechanisms by which B7-H3 remodels the tumor microenvironment. We performed gene expression profiling analysis using data generated from RNA-seq of bulk tumors from subcutaneous B7-H3 knockdown and control TSC2-deficient 105K cells or sorted tumor cells isolated by MACS mouse tumor cell isolation kit (Miltenyi Biotec).

overall_design: Comparative mRNA expression profiling analysis of RNA-sequencing from bulk tumors or sorted tumor cells isolated from wild-type C57BL/6J mice carrying subcutaneous TSC2-deficient B7-H3 knockdown or control tumors.

first: Heng

last: Du

first: Damir

last: Khabibullin

first: Mahsa

last: Zarei

first: Kevin

last: Wei

first: Gordon

middle: J

last: Freeman

first: David

last: Kwiatkowski

first: Elizabeth

middle: P

last: Henske


title: Nucleus pulposus related lncRNA and mRNA expression profiles in intervertebral     disc degeneration

city: Guangzhou

first: Yanjiao

last: Wu

state: Guangdong

address: street address: No.1023,South Shatai Road, Baiyun District

institute: Southern Medical University

summary: Intervertebral disc degeneration (IDD) leads to low back pain and disability     globally. The pathophysiology of IDD is not entirely understood. There is     increasing evidence that long noncoding RNAs (lncRNAs) play a key regulatory role     in a wide range of biological processes. The purpose of this study was to     comprehensively lncRNA and mRNA expression profiles of human intervertebral disc     (IVD) tissues, specifically nucleus pulpous (NP) tissues, with early and advanced     stages of disc degeneration. The overview of lncRNA and mRNA expression profiles     in the current study revealed that differentially expressed lncRNAs and mRNAs     were identified that have been reported to be relevant to IDD. Importantly,     differentially expressed lncRNAs and mRNAs that regulate the major signaling     pathways, such as NF-κB, MAPK, and Wnt signaling, that are well known to be     responsible for the pathogenesis of IDD.

overall_design: Human NP tissues obtained from spine surgeries were used in this study. The samples were divided into two groups: early stage degeneration (n=3, Pfirrmann’s MRI grade: I-III) and advanced stage degeneration (n=3, grade: IV-V). we conducted lncRNA and mRNA profiling in 3 human control nucleus pulposus tissue and 3 degenerative nucleus pulposus tissue by RNA sequencing (RNA-seq).

first: Huan

first: Sen

last: Li


title: Location of NFIA-ETO2 binding site on genome in MEL cells

first: Jonathan

type: Genome binding/occupancy profiling by high throughput sequencing

summary:
The NFIA-ETO2 fusion is the product of a t(1;16)(p31;q24) chromosomal translocation so far exclusively found in pediatric patients with pure erythroid leukemia (PEL). To address its role for the pathogenesis of the pure erythroid leukemia, we retrovirally expressed the PEL-associated NFIA-ETO2 fusion in MEL cells.
To better identify direct target gene loci, we sequenced NFIA-ETO2-associated immunoprecipitated chromatin and histone modifications.

overall_design: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for HA NFIA-ETO2 tag, IGG and histone modifications H3K27ac, H3K4me1, H3K27me3 and H3K9me1 in MEL cells expressing or not NFIA-ETO2.


title: Adaptive laboratory evolution of chorismate synthase knockouts

city: La Jolla

first: Cameron

last: Lamoureux

state: CA

address: 9500 Gilman Drive

department: Bioengineering

institute: University of California San Diego

summary: We used RNA-seq to profile E. coli K-12 MG1655 strains subjected to adaptive laboratory evolution after chorismate synthase knockouts. Either isochorismate synthase (menF) or isochorismate synthase AND chorismate lyase (ubiC) was deleted from a strain of E. coli K-12 MG1655 that had already been previously adapted for growth on glucose minimal media. RNA-seq profiles of the original glucose-adapted strain, the 2 deletion strains, and 4 laboratory-evolved strains from each deletion are included in duplicate. ubiC catalyzes the first committed step of ubiquinone synthesis, an important molecule for the electron transport chain. Thus, these experiments allowed assessment of cellular adaptations to restore energy metabolism capability.

sample_organism: Escherichia coli str. K-12 substr. MG1655

overall_design: Growth of E. coli was performed with biological duplicates. Total RNA was extracted from mid-log phase culture for RNA-Seq library preparation.

first: Amitesh

last: Anand


title: The NFIA-ETO2 fusion blocks terminal erythroid maturation and induces pure erythroid leukemia in cooperation with mutant TP53

last: Seguin

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

overall_design: Refer to individual Series


title: Lipid-accumulated reactive astrocytes promote seizure activity in epilepsy [KA and APOE]

city: Nanjing

first: Dijun

last: Chen

state: Jiangsu

address: Xianlin

department: Life Sciences

institute: Nanjing University

summary: Abnormal lipid accumulation have been reported in patients with temporal lobe epilepsy (TLE) by in vivo magnetic resonance imaging (MRI). However, the role of astrocytes in the regulation of neuronal activity or lipid metabolism in epilepsy is unclear. Using single-nucleus RNA sequencing of TLE patient samples, we found lipid accumulation and lipid metabolism dysfunction mainly take place in astrocytes. Mechanistic studies revealed that apolipoprotein E (APOE) mediates lipid transfer from hyperactive neurons to astrocytes, turning them into the neurotoxic reactive phenotype

overall_design: 3 KA-induced TLE model; 6 KA-induced TLE model and treated with KA; 6 KA-induced TLE model and treated with KA and APOE

first: Chao

last: Yan

first: Xiangyu

first: Zhangpeng

first: Wen

last: Fang


title: Maternal Nutritional Status Modifies Heat-Associated Growth Restriction in Women with Chronic Malnutrition

city: College Station

first: Kartik

last: Shankar

email: kartik.shankar@cuanschutz.edu, kartikster@gmail.com, kartik.shankar@usda.gov, kartik.shankar@ag.tamu.edu

state: TX

address: 498 Olsen Blvd TAMU 2250 TAMU 2250

department: RAFSRU

institute: USDA ARS

summary: Rising ambient temperatures represent an imminent risk to pregnant women and infants. Both maternal malnutrition and heat stress during pregnancy contribute to poor fetal growth, the leading cause of diminished child development in low-resource settings. However, studies explicitly examining interactions between these two important environmental factors are lacking. We leveraged maternal and neonatal anthropometry data from a randomized controlled trial focused on improving preconception maternal nutrition (Women First Preconception Nutrition trial) conducted in Thatta Pakistan, where both nutritional deficits and heat stress are prevalent. Multiple linear regression of ambient temperature and neonatal anthropometry at birth (n = 459) showed a negative association between daily maximal temperatures in the first trimester and z-scores of birth length (LGAZ) and head circumference (HCGAZ). Placental mRNA-sequencing and protein analysis showed transcriptomic changes in protein translation, ribosomal proteins and mTORC1 signalling components in term placenta exposed to excessive heat in the first trimester. Targeted metabolomic analysis indicated ambient temperature associated alterations in maternal circulation with decreases in choline concentrations. Notably, negative impacts of heat on birth length were in part mitigated in women randomized to comprehensive maternal nutritional supplementation (MNS) before pregnancy suggesting potential interactions between heat stress and nutritional status of the mother. Collectively the findings bridge critical gaps in our current understanding of how maternal nutrition may provide resilience against adverse effects of heat stress in pregnancy.

overall_design: RNA was extracted from placenta tissue at term using a combination of TRI reagent and cleanup with Qiagen Rneasy columns.

first: Nancy

last: Krebs


title: Assaying for RNA abundance and protein phosphorylation in pooled CRISPR screens

city: Berlin

first: Oriana

last: Genolet

address: Ihnestrasse 63

department: OWL Schulz

country: Germany

institute: Max Planck Institute for Molecular Genetics

summary: Pooled CRISPR screens are a powerful tool to identify regulators of a biological process, but have been limited to phenotypes that affect viability or can be monitored with fluorescent protein reporters. We evaluate two additional strategies for phenotypic enrichment based on quantification of RNA using a Flow-FISH assay or protein phosphorylation through intracellular phospho-staining. These tools will greatly expand the applicability of CRISPR screens since they increase the number of possible molecular phenotypes and assay designs.

sample_organism:
Mus musculus
synthetic construct

platform_organism:
Mus musculus
synthetic construct

overall_design: Pooled Knockout CRISPR screen comparing Nanog Flow-FISH vs a C-terminally tagged mCherry Nanog reporter and an intracellular pMek-staining vs a live MAPK GFP reporter as readout systems. An sgRNA library targeting annotated phosphatases is implemented.

first: Liat

last: Ravid-Lustig

first: Edda

middle: G

last: Schulz


title: Ponatinib-induced cardiotoxicity is driven by S100A8/A9-NLRP3-IL-1β signaling mediated excessive inflammation

city: Pittsburgh

first: Cristi

middle: Lara

last: Galindo

state: Pennsylvania

address: 200 Lothrop Avenue

institute: University of Pittsburgh

summary:
To delineate the underlying molecular mechanisms of ponatinib-induced cardiotoxicity, we used we a comorbitity cardiotoxicity mouse model (high fat-fed ApoE-/- mice) treated for two weeks with placebo/ or Ponatinib
We then performed gene expression profiling analysis on left ventricular tissues from the two mouse groups

overall_design: Comparative gene expression profiling analysis of RNA-seq data for Placebo or Ponatinib-treated high fat-fed ApoE-/- mice

first: Tousif

last: Sultan

first: Hind

last: Lal


title: Transcriptome profiling of Burkholderia pseudomallei wildtype strain1026b and BP1026b_II1046::T4 insertion mutant

city: Honolulu

first: Tung

last: Hoang

state: Hi

address: 1800 East-west Road

department: School of life sciences

institute: University of Hawaii at Manoa

summary: We identified BP1026b_II1046 (SapR) to be an important transcriptional regulator controling surface attachment factor 1 (sap1). RNA-seq analysis was performed to further investigate the regulatory network of SapR regulation.

overall_design: Differential gene expression analysis of SapR mutant and Bp wildtype

first: Zhenxin

last: Sun

first: Yun

last: Heacock-Kang


title: Early onset colorectal cancer tissues and late onset colorectal cancer tissues

city: Deajeon

first: YunJae

last: Shin

state: Deajeon

address: 125, Gwahak-ro, Yuseong-gu, 34141 Daejeon, South Korea

country: South Korea

institute: Korea Research Institute of Bioscience and Biotechnology

summary:
To identify the gene expression of early-onset colorectal cancer, we sampled early-onset colorectal cancer patients (age < 50) and late-onset colorectal cancer paitients (age > 70)
We then performed gene expression profiling analysis using data obtained from RNA-seq of early-onset colorectal cancer tissues and late-onset colorectal cancer tissues.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for early-onset colorectal cancer tissues and late-onset colorectal cancer tissues.

first: Chan

middle: W

last: Kim

first: Ye

last: Ha


title: Long Non-Coding RNA LEENE Promotes Angiogenesis and Ischemic Recovery (scRNA-Seq)

city: Duarte

first: Zhen

last: Chen

address: 1500 E Duarte Rd

department: DMRI

institute: City of Hope

summary: To test the function of LEENE in leene-KO mice and delineate the contribution of LEENE RNA in the ischemic response, we supplemented the leene-KO mice with human LEENE RNA and performed single cell RNA-seq. The transcriptome of the EC-enriched fractions in the ischemic muscles was profiled at the single cell level.

overall_design: The leene-KO mice with Hindlimb ischemia (HLI) were supplemented with adenovirus overexpressing GFP or human LEENE via muscle injection. The ischemic muscles were dissected, endothelial cells were isolated and enriched by CD144 beads. Single cell RNA-seq was performed by using the 10XGenomics 3’ gene expression assay.

first: Xiaofang

last: Tang

first: Yingjun

last: Luo

first: Dongqiang

last: Yuan

middle: B


title: Identification of novel pathways regulated by APE1/Ref-1 in human retinal endothelial cells

city: Indianapolis

first: Kelley

last: Mark

state: Indiana

institute: Herman B Wells Center for Pediatric Research

summary: We used RNA seq tool to identfiy key signaling pathways affected by APE1/Ref-1 in HRECs, which was contrasted to RNA seq data of tumor cell lines.

overall_design: We used siRNA to knock down (KD) APE1/Ref-1 protein in HRECs  and performed RNA seq analysis, which was then validated by qRT-PCR.

first: Sheng

last: Liu

first: Jun

last: Wan

first: Mahmut

last: Mijit

first: Mark

middle: R

last: Kelley

first: Kamakshi

last: Sishtla

first: Gabriella

middle: D

last: Hartman

first: Timothy

last: Corson


title: Cre-recombinase expression cooperates with FLT3ITD/ITD to induce acute myeloid leukemia [RNASeq_SclCre_JQ1_vs_vehicle]

city: Brisbane

first: Jasmin

last: Straube

state: QLD

address: 300 Herston Rd

country: Australia

institute: QIMR Berghofer

summary: Animal models offer a valuable tool to recapitulate genetically defined subtypes of AML, and to assess the potential of compound mutations and clonal evolution during disease progression. This is of utmost importance for difficult to treat leukemias such as FLT3-ITD positive AML. While conditional gene targeting by Cre-recombinase is a powerful technology that has revolutionized biomedical research, consequences of Cre-expression such as lack of fidelity, toxicity or off-target effects need to be taken into consideration. We report on a transgenic murine model of FLT3-ITD induced disease, where Cre-recombinase expression alone, and in the absence of a conditional allele, gives rise to an aggressive leukemia phenotype. Here, expression of various Cre-recombinases leads to polyclonal expansion of FLT3ITD/ITD progenitor cells, induction of a differentiation block and activation of Myc-dependent gene expression programs. Our report is intended to alert the scientific community of potential risks associated with using this specific mouse model and of unexpected effects of Cre-expression when investigating cooperative oncogenic mutations in murine models of cancer.

overall_design: Mice were competitive transplanted with Scl-CreERT:Flt3ITD/ITD CD45.2 Kit+ spleenocytes leukemic splenocytes (5x10^6) mixed with CD45.1 C57BL/6 bone marrow (5x10^5). After 4 weeks high WBC was confirmed prior to treatment with JQ1 (50mg/kg) or vehicle. After 4 hours spleens were extracted and cells FACS sorted for (Kit+CD45.2+CD45.1-).

first: Therese

last: Vu

first: Steven

last: Lane


title: Cre-recombinase expression cooperates with FLT3ITD/ITD to induce acute myeloid leukemia [RNASeq_SclCre_Spleen]

overall_design: Scl-CreERT:Flt3ITD/ITD and control mice  were treated 2 weeks with tamoxifen to induce Cre expression.  At disease onset spleens were extracted and cells FACS sorted for (LKs; Lineage-Kit+).


title: Gene expression studies of WT1 mutant Wilms tumor cell lines in the frame work of published kidney development data reveals their early kidney stem cell origin

city: Duesseldorf

first: Brigitte

last: Royer-Pokora

address: Universitätsstr. 1

institute: Institute of Human Genetics and Anthropology, Heinrich-Heine-University Duesseldorf

type:
Expression profiling by array
Third-party reanalysis

summary: In order to get a better insight into the timing of WT1 mutant Wilms tumor development, we compared the gene expression profiles of nine established WT1 mutant Wilms tumor cell lines with published data from different kidney cell types during development. Publications describing genes expressed in nephrogenic precursor cells, ureteric bud cells, more mature nephrogenic epithelial cells and interstitial cell types were used. These studies uncovered that the WT1 mutant Wilms tumor cells lines express genes from the earliest nephrogenic progenitor cells, as well as from more differentiated nephron cells with the highest expression from the stromal/interstitial compartment. The expression of genes from all cell compartments points to an early developmental origin of the tumor in a common stem cell. Although variability of the expression of specific genes was evident between the cell lines the overall expression pattern was very similar. This is likely dependent on their different genetic backgrounds with distinct WT1 mutations and the absence/presence of mutant CTNNB1.

overall_design: 3 different Wilms tumor cell lines with WT1 mutations and additional CTNNB1 mutations - Wilms6 (4 replicates), Wilms8 (2 replicates), Wilms10-M (2 replicates)- were analyzed together with Wilms tumor cell lines from GSE18058 and GSE71265.

first: Wasco

last: Wruck

first: James

last: Adjaye

first: Manfred

last: Beier


title: Cre-recombinase expression cooperates with FLT3ITD/ITD to induce acute myeloid leukemia [RNASeq_Mx1Cre_BM]

overall_design: Mx1-Cre:Flt3ITD/ITD, Flt3ITD/ITD other control mice were injected with pIpC  to induce Cre expression two times every second day intraperitoneally. Injections were halted if mice showed signs of illness prior to completion of treatment.  Bone marrow was extracted and cells FACS sorted for haematopoietic  stem and progenitor cells (LSKs; Lineage-Sca1+Kit+).

first: Florian

last: Heidel

first: Tina

last: Schnoeder


title: Cre-recombinase expression cooperates with FLT3ITD/ITD to induce acute myeloid leukemia [RNASeq_SclCre_BM]

overall_design: Scl-CreERT:Flt3ITD/ITD and control mice  were treated 2 weeks with tamoxifen to induce Cre expression.  After 2 weeks post treatment bone marrow was extracted and cells FACS sorted for haematopoietic  stem and progenitor cells (LSKs; Lineage-Sca1+Kit+).


title: Long Non-Coding RNA LEENE Promotes Angiogenesis and Ischemic Recovery (ChIRP-Seq)

first: Zhen

last: Chen

summary: Chromatin-associated long non-coding RNAs (ca-lncRNAs) play important roles in transcriptional regulation. To comprehensively investigate the chromatin interactome of an enhancer-derived ca-lncRNA, LEENE, we performed the Chromatin isolation by RNA purification (ChIRP) to pull down LEENE-associated DNAs, which were subjected to DNA-seq. Specifically, we used 10 previously validated tiling nucleotides targeting different domains based on the predicted secondary structure. LEENE was overexpressed by adenovirus to enhance the ChIRP-seq signals.

overall_design: Chromatin isolation by RNA purification from HUVEC treated with Adenovirus-overexpressing GFP or LEENE for 3 days, followed by DNA-seq.

first: Xiaofang

last: Tang

first: Yingjun

last: Luo

first: Dongqiang

last: Yuan


title: Cre-recombinase expression cooperates with FLT3ITD/ITD to induce acute myeloid leukemia [ATAC-Seq]

overall_design: Chromatin profiles using ATAC-Seq of hematopoietic stem and progenitor cells (LSK+) were generated post tamoxifen induced Cre-Recombinase expression when mice presented with AML or age matched controls.


title: Cre-recombinase expression cooperates with FLT3ITD/ITD to induce acute myeloid leukemia


title: Transcriptional Responses Define Dysregulated Immune Activation in Hepatitis C (HCV)-Naïve Recipients of HCV-Infected Donor Kidneys

city: Durham

first: Julie

last: Steinbrink

state: NC

address: 310 Trent Drive

department: Medicine

institute: Duke Department of Medicine

summary: In this study, we evaluated transcriptional responses in circulating leukocytes to  assess for biomarkers of adverse outcomes in transplant patients after transplantation from a HCV-infected donor. We enrolled renal transplant recipients with and without HCV and performed RNA sequencing on serial samples. CMV DNAemia and allograft rejection outcomes were measured. Regularized logistic regression was utilized to develop gene expression classifiers predictive of clinical outcomes.

overall_design: 67 renal transplant recipients  were included in this analysis (30 controls, 37 HCV recipients); serial samples were collected from the first month after transplant, 3 months post-transplant, and 6 months post-transplant; total RNA was extracted from human blood by PAXgene and RNA sequencing was performed.

middle: M

first: Micah

middle: T

last: McClain

first: Cameron

last: Miller

first: Rachel

last: Myers


title: Long Non-Coding RNA LEENE Promotes Angiogenesis and Ischemic Recovery (ChIP-Seq)

summary: The response of endothelial cells to diabetic-simulating stimuli is poorly understood. To evaluate the changes of enhancer activation status in HUVEC, genome-wide enrichment of H3K27ac (marker of enhancer and open chromatin) was examined in HUVECs treated with combined high glucose and TNF-alpha. HUVECs incubated in 25 mM mannitol were used as osmolarity control.

overall_design: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for histone modifications H3K27ac in HUVEC treated by 25 mM glucose and 5 ng/ml TNFa for 3 and 7 days

first: Kiran

last: Sriram


title: Sunitinib efficacy with minimal toxicity in patient-derived organoid models of retinoblastoma

city: Bangkok

first: Rossukon

last: Kaewkhaw

address: 270 Rama VI Road Ratchathewi

country: Thailand

institute: Mahidol University

summary: Background. Recurrence or persistence of retinoblastoma (RB) is common following chemoreduction and often be managed with intra-arterial/ intravitreal chemotherapy. However, no/minimal response to local chemotherapy has been documented, with enucleation needed for tumor control. Otherwise, the globe is preserved with effective tumor control but at the cost of vision due to retinal toxicity. The aim of this study was to discover novel drug with improved antitumor activity and retinal safety profiles for RB via drug reprofiling in patient-derived tumor organoids.  Methods. Five tumor organoid lines were fully characterized using CGH/SNP array and whole exome sequencing and used as a model to test 133 FDA-approved compounds using two-step screening processes. RNA sequencing was conducted to generate drug signature in conjunction with cell cycle and apoptotic assays. An ability of candidate drug to restrict proliferative tumor cone were examined together with retinal toxicity testing in human ESC-derived retinal organoids, in comparison with clinically used drugs by immunostaining.  Results. Sunitinib was identified as high cytotoxic agent for the classical RB1-deficient and novel MYCN-amplified RBs. Gene signature indicated that anti-tumoral activity of sunitinib was associated with MAPK activity. Additionally, sunitinib was more effective to suppress proliferative tumor cones and had less retinal toxicity compared with melphalan and topotecan.   Conclusions. Sunitinib may be a “universal” drug for all subtypes of RB. With high efficacy and low retinal toxicity, sunitinib is potential agent used in local chemotherapy for treating RB.

overall_design: Duplicate samples each of two different suptypes of retinoblastoma cells were treated with sunitinib. Duplicate samples without sunitib treatment serve as a control.

first: Vijender

last: Chaitankar


title: Transcriptomic comparison between  nlp2-2, nlp2-3, nlp7-1, nlp2-3 nlp7-1 mutants and WT.

city: Versailles

first: Mickael

last: Durand

address: Route de St-Cyr (RD10)

department: IJPB

country: France

institute: INRAE

summary: RNA-seq was performed on shoot and root from 42 day-old plants of nlps mutants and WT grown on sand under non-limiting nitrate supply (5mM).

overall_design: Genome-wide profiling of nlps mutants by RNA-seq, 3 biological replicates

first: Anne

last: Krapp


title: The NFIA-ETO2 fusion blocks terminal erythroid maturation and induces pure erythroid leukemia (PEL)

city: Basel

first: Jonathan

last: Seguin

address: Spitalstrasse 33

institute: UKBB-DBM

summary:
The NFIA-ETO2 fusion is the product of a t(1;16)(p31;q24) chromosomal translocation so far exclusively found in pediatric patients with pure erythroid leukemia (PEL). To address its role for the pathogenesis of the pure erythroid leukemia, we retrovirally expressed the PEL-associated NFIA-ETO2 fusion in primary erythroblasts in fetal liver-derived erythroblasts from wild-type (C57/B6) mice.
To better characterize alteration in chromatin accessibility due to NFIA-ETO2 expression, we analyzed  accessible chromatin state by ATAC sequencing from cells kept in 24h in differentiation-inducing medium (DM)

overall_design: Assay for Transposase-Accessible Chromatin DNA-sequencing (ATAC-seq) for primary erythroblast cells which express NFIA-ETO2 or not (control).

first: Maria-Riera

last: Piqué-Borràs

first: Frederik

last: Otzen Bagger

first: Robert

last: Ivanek

first: Juerg

last: Schwaller


title: Long Non-Coding RNA LEENE Promotes Angiogenesis and Ischemic Recovery (RNA-Seq I)

first: Zhen

last: Chen

summary: Vascular endothelial cells play a pivotal role in whole-body homeostasis. To test the function of human long non-coding RNA LEENE in Human umbilical vein endothelial cells (HUVEC), we inhibited LEENE by using a previously validated locked nucleic acid (LNA) GapmeR under pulsatile flow which mimics the physiological state and is characterized by elevated LEENE levels. PolyA-enriched RNA-seq was performed to examine the LEENE-regulated gene expression.

overall_design: PolyA-enriched RNA-seq in HUVEC with LEENE knockdown by LNA

first: Xiaofang

last: Tang


title: Alterations in gonadotropin, apoptotic and metabolic pathways in granulosa cells warrant superior fertility of the Dummerstorf high fertility mouse line 1 (FL1)

city: Bonn

first: Ulrich

last: Schweizer

state: NRW

address: Nussallee 11

department: Institut für Biochemie und Molekularbiologie

institute: Universitätsklinikum Bonn

summary: During the last decades, several mouse models provided insights into the regulation of folliculogenesis. In contrast to the commonly used transgenic or knockout mouse models, the Dummerstorf high-fertility mouse line 1 is a worldwide unique selection experiment for increased female reproductive performance and high fertility. These mice are characterized by various alterations on endocrine and molecular levels, which have the potential to improve folliculogenesis and therefore lead to increased ovulation rates. To get insights into the cellular mechanisms leading to the high fertility phenotype we used granulosa cells isolated from antral follicles for mRNA sequencing and measured hormones and growth factors associated with follicular development.  Our results indicate that the crosstalk between different intracellular signaling pathways in the granulosa cells are improved, follicular atresia in FL1 might be decreased due to enhanced granulosa cell survival and by improving the efficiency of intracellular signaling, glucose metabolism and signal transduction, FL1 mice have several advantages in reproductive performance and therefore increased the ovulation rate without health issues.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for granulosa cells isolated from antral follicles derived from Dummerstorf ctrl and FL1 mice

first: Carolin

last: Ludwig

first: Simon

last: Bohleber

first: Joachim

last: Weitzel


title: Lipid-accumulated reactive astrocytes promote seizure activity in epilepsy [mouse]

first: Dijun

summary: Abnormal lipid accumulation have been reported in patients with temporal lobe epilepsy (TLE) by in vivo magnetic resonance imaging (MRI). However, the role of astrocytes in the regulation of neuronal activity or lipid metabolism in epilepsy is unclear. Using single-nucleus RNA sequencing of TLE patient samples, we found lipid accumulation and lipid metabolism dysfunction mainly take place in astrocytes. Mechanistic studies revealed that apolipoprotein E (APOE) mediates lipid transfer from hyperactive neurons to astrocytes, turning them into the neurotoxic reactive phenotype

overall_design: Examination of 26 epileptic sample and 26 non-epileptic control samples

first: Chao

last: Yan

first: Xiangyu

last: Liu

first: Zhangpeng

first: Wen

last: Fang


title: Transcription factor ZBTB7A-deficiency effect on U87MG cells in vitro

city: Seoul

first: Ji-Hoon

last: Jeong

address: 88, Olympic-ro 43-gil, Songpa-gu

department: Biomedical Sciences

institute: University of Ulsan College of Medicine

summary: Analysis of glioblastoma cell line U87MG depleted for ZBTB7A (Zinc Finger and BTB Domain Containing 7A, also known as FBI1, POKEMON or LRF). ZBTB7A is transcription factor that represses the transcription of a wide range of genes involved in cell proliferation and differentiation. Results provide insight into the role of ZBTB7A in glioblastoma.

overall_design: For expression of ZBTB7A, a control vector (pLKO) and shZBTB7A were infected in U87MG cell line, and stable expression was induced through puromycin.

first: Seung-Ho

last: Park

first: Kyung-Chul

last: Choi


title: Lipid-accumulated reactive astrocytes promote seizure activity in epilepsy [Human bulk RNA-seq]

overall_design: Examination of 3 TLE patents sample and 3 non-epileptic control patients


title: Co-targeting leukemia-initiating cells and leukemia bulk leads to disease eradication

city: milano

first: Saverio

last: Minucci

address: via Adamello 16

country: Italy

institute: European Institute of Oncology

summary: Co-targeting the plasticity and heterogeneity of cancer is fundamental to achieve and maintain complete remission (CR). We exploited murine models of acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia driven by the promyelocytic leukemia/retinoic acid receptor (PML-RARα) oncofusion protein, which recruits histone deacetylase (HDAC)-containing complexes. We investigated the effect of two HDAC inhibitors: valproic acid (VPA), and SAHA/vorinostat with all-trans retinoic acid (ATRA), on the bulk cells and LICs of two APLs with different LIC frequencies. VPA and SAHA selectively target the bulk APL cells and LICs respectively. VPA+SAHA+ATRA combination induced CR in an APL model with lower LIC frequency.

overall_design: Genome-wide transcriptomic analysis of two acute promyelocytic leukemic clones with different LIC frequencies

first: Simona

last: Moretti

first: Amal

middle: K

last: Abdel-Aziz

first: Elena

last: Ceccacci

first: Isabella

last: Pallavicini

first: Fabio

last: Santoro

first: Hugues

last: de Thé


title: Transcriptional and functional characterization of human intestinal organoid and monolayer models for IBD-therapeutic development

city: Cambridge

first: Scott

last: Jelinsky

state: MA

address: 610 Main Street

department: Inflammation and Immunology

institute: Pfizer

summary: Intestinal organoids have the potential to replicate cellular diversity and functional biology of the human gut, suggesting their application in Inflammatory Bowel Disease (IBD) research. Insufficient characterization at the molecular, cellular, and functional level has remained a barrier to their use in drug discovery. We profile intestinal organoids and Transwell-monolayers derived from ileum and colon tissue of control and IBD subjects. Organoids and monolayers respond to optimized differentiation media with consistent expression and maturation patterns, including signatures of epithelial cell types found in the human gut. Both ileum- and colon-derived monolayers show acute sensitivity to cytokines with applicability  for modeling epithelial barrier damage.

overall_design: Instestinal organoid and monolayer cultures derived from healthy and IBD colon and ileum where grown in three different differentiation media


title: Differential expression of extracellular vesicles-derived long RNA sequencing of plasma from patients after myocardial infarction with or without cardiac remodeling and healthy individuals

city: Guangzhou

first: shuai

last: mao

address: Dade Road

institute: Guangzhou University of Chinese Medicine

type: Non-coding RNA profiling by high throughput sequencing

summary:
The goals of this study are to compare extracellular vesicles-derived circRNAs-lncRNAs-mRNA(RNA-seq) from the plasma of myocardial infarction patients with cardiac remodeling (C), without cardiac remodeling (NC), and normal healthy people (N).
Human plasma was separated by centrifugation at 3,000 rpm for 10 min at room temperature (25°C) within 2 h after blood collection and then centrifuged at 13,000 rpm for 10 min at 4°C to remove debris. Isolated plasma samples were stored at -80°C until use. Extracellular vesicles RNA were isolated by affinity-based binding to spin columns using an exoRNeasy Serum/Plasma kit (Qiagen, Hilden, Germany). RNA libraries were prepared for sequencing using SMARTer Stranded Total RNA-Seq Kit - Pico Input Mammalian. RNA-seq was performed by the Illumina NovaSeq 6000 on a 150-bp paired-end run.

overall_design: Extracellular vesicles-derived long RNA profiles of patients after myocardial infarction with cardiac remodeling (C), without cardiac remodeling (NC) and normal healthy individuals (N) by deep sequencing using Illumina NovaSeq 6000

first: Shuai

last: Mao

first: Minzhou

last: Zhang


title: Long Non-Coding RNA LEENE Promotes Angiogenesis and Ischemic Recovery (RNA-Seq II)

first: Zhen

last: Chen

summary: Vascular endothelial cells play a pivotal role in whole-body homeostasis. To test the function of LEENE in leene-KO mice and delineate the contribution of LEENE RNA in the ischemic response, we supplemented the leene-KO mice with human LEENE RNA and profiled the transcriptomic changes in the EC-enriched fractions of the ischemic muscles.

overall_design: PolyA-enriched RNA-seq in ischemic muscle endothelial cells of leene-KO mice supplemented with human LEENE

first: Xiaofang

last: Tang

first: Yingjun

last: Luo

first: Riccardo

last: Calandrelli

first: Dongqiang

last: Yuan


title: Lipid-accumulated reactive astrocytes promote seizure activity in epilepsy

city: Nanjing

first: Dijun

address: Xianlin

institute: Nanjing University

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

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Refer to individual Series


title: Lipid-accumulated reactive astrocytes promote seizure activity in epilepsy [single-cell RNA-seq]

overall_design:
Examination of 4 TLE patents sample and 4 non-epileptic control patients

>>>Raw data not provided due to patient privacy concerns<<<

first: Chao

last: Yan

first: Xiangyu

last: Liu

first: Zhangpeng

first: Wen

last: Fang


title: Long Non-Coding RNA LEENE Promotes Angiogenesis and Ischemic Recovery


title: Discovery and characterization of LNCSOX17 as an essential regulator in endoderm formation

city: Berlin

first: Helene

last: Kretzmer

address: Ihnestraße 63

department: Genome Regulation

institute: Max Planck Institute for Molecular Genetics

summary: Long noncoding RNAs (lncRNAs) have emerged as fundamental regulators in various biological processes, including embryonic development and cellular differentiation. Despite much progress over the past decade, the genome-wide annotation of lncRNAs remains incomplete and many known non-coding loci are poorly characterized. Here we report the discovery of a previously not annotated lncRNA that is transcribed 230 kb upstream of the SOX17 gene and located within the same topologically isolated domain. We therefore termed it LNCSOX17 and show that it is induced following SOX17 activation, but is more tightly restricted to early definitive endoderm than SOX17. Notably, loss of LNCSOX17 affects crucial functions independent of SOX17 and leads to an aberrant endodermal transcriptome, signaling pathway deregulation, and epithelial to mesenchymal transition defects. Consequently, cells lacking LNCSOX17 cannot further differentiate into more mature endodermal cell types. Our study identified LNCSOX17 and demonstrates its essential role as a new actor in early human endoderm, thereby further expanding the list of functionally important non-coding regulators.

overall_design: cHi-C seq, 4C seq, RNAseq, ChIPseq and Oxford Nanopore cDNA seq were performed on hiPSCs/hESCs (day0), hiPSCs/hESCs derived endoderm (day5), intermediate differentiation stage (day3) or pancreatic progenitors (day9). Cells were grown as described in the methods section or in the protocol sections below. Libraries have been performed following manufacturer instructions and how described in the methods section or below.

first: Alexandro

last: Lanshammer

first: Adriano

last: Bolondi

first: Christian

last: Much

first: René

last: Buschow

first: Alina

last: Rose

first: Jack

last: Huey

first: Krishna

last: Parsi

first: Hua-Jun

last: Wu

first: Sebastian

last: Mackowiak

first: Bjoern

last: Braendl

first: Pay

last: Giesselmann

first: Denes

last: Hnisz

first: Franziska

last: Michor

first: Bernd

last: Timmermann

first: Thorsten

last: Mielke

first: Rene

last: Maehr

first: John

last: Rinn

first: Alexander

last: Meissner


title: The chromatin dynamics of the TFAP2A/ MITF genetic interaction in melanocyte development.

city: Iowa City

first: Colin

last: Kenny

state: Iowa

address: 51 Newton Road 100 Bowen Science Building Iowa

department: Anatomy and Cell Biology

institute: University of Iowa

summary: We have deleted TFAP2A and its redundantly-acting paralog TFAP2C in human melanoma SkMel28 cell lines and are assessing MITF binding using Cleavage Under Targets and Release Using Nuclease (CUT&RUN). Conversely, we deleted all copies of MITF in SkMEL28 cells and are similarly profiling TFAP2A bound loci. We predict TFAP2A functions as a pioneer factor for MITF during melanocyte development and that in the absence of TFAP2A, MITF binding at loci normally co-bound by MITF/TFAP2A will be disrupted.

overall_design: We targeted TFAP2A and MITF by CUT&RUN sequencing in wild-type, MITF knockout and TFAP2A; TFAP2C double knockout (two independent clones) SkMel28 cell lines. All experiments were conducted in duplicate. IgG was used as a background control.


title: Differential angiogenesis of bone and muscle endothelium in aging and inflammatory processes

city: Biella

first: Paola

last: Ostano

address: via Malta 3

institute: Fondazione Edo ed Elvo Tempia

summary: Trnascription profiling of primary endothelial cells isolated from leftover material (bone and muscle tissues).

overall_design: Gene expression profiling of putative endothelial cells derived from bone or muscle and of negative cells left after immunoselection.

first: Chiara

last: Arrigoni

first: Simone

last: Bersini

first: Martina

last: Crippa

first: Maria

middle: V

last: Colombo

first: Mara

last: Gilardi

first: Luigi

last: Zagra

first: Carmen

last: Ghilardi

last: Bani

first: Christian

last: Candrian

first: Giovanna

last: Chiorino

first: Matteo

last: Moretti


title: Analysis of NCOR2 function in astrocytes

city: Boston

first: Zhaorong

last: Li

address: 60 Fenwood Road

institute: Dana Farber Cancer Institute

summary: We identify pathways regulated by Ncor2 in astrocytes during EAE

overall_design:
sgScrmbl-targeted (n=3) and sgNcor2-targeted (n=3) mice

Samples were analyzed by PACS from WT or EAE mice

Analysis of NR3C2 function in astrocytes

We identify pathways regulated by XBP1 in astrocytes during EAE

first: Iain

last: Clark

first: Francisco

last: Quintana

first: Michael

last: Wheeler


title: Loss of Tet proteins impairs mouse embryonic stem cells differentiation toward cardiomyocytes progenitors

city: Houston

first: Jia

state: Texas

address: 2121 W HOLCOMBE BLVD

department: CEDP

institute: Guangzhou Medical University

summary: DNA methylation mediated epigenetic regulation plays a critical role in regulating cardiomyocytes (CM) differentiation. Tet protein mediated DNA methylation oxidation have been reported to play an important role in regulating embryonic stem cell (ESC) differentiation toward different lineages. In our study, we utilized CRISPR/Cas9 based genome editing method to generated Tet single, double and triple deficient mouse ESC (mESC) expressing emGFP under NKX2.5 promoter and differentiated these cells toward CM progenitors. By modulating emGFP population as cardiac progenitor cells, we found that deletion of Tet1 and Tet2 significantly impairs mESC differentiation toward CM progenitors. Further single-cell RNA-seq analysis in differentiated control and Tet-triple knockout (TKO) mESC reveals that Tet deletion resulted in accumulation of mesoderm progenitors and impairs CM differentiation. Overexpression the catalytic domain of Tet1 could rescue the development defects in Tet-TKO mESC and restore NKX2.5 gene expression. In addition, loci-specific dCas9-Tet1CD mediated epigenome editing at Hand1 loci confirmed its directly transcriptional regulation during CM differentiation. Overall, out studies suggested that Tet protein mediated epigenomic remodeling is a genome-wide event and is essential to maintain proper transcription network during mESC differentiation toward CM progenitors.

overall_design: In this study, we systematically investigated  the roles of TET proteins in mESC differentiation toward cardiac lineage process. We compared the 5hmC profiles in mESC day0, day2 and day5. We also compared the scRNAseq data between WT and TKO mESC at differentiation day5.

first: Yun

last: Huang


title: Identification of causal genes about osteoporosis associated with risk loci using DLO Hi-C

city: Wuhan

first: LI

last: LI

state: Hubei

address: 185 Donghu Road

institute: wuhan university school of basic medical sciences


title: SCD1 Modulates the Skin Homeostasis via Sustaining Hemidesmosomes

city: Shanghai

first: Yueqing

last: Xue

state: 上海市

address: 319 Yueyang Road

institute: Shanghai Institute of Nutrition and Health

summary: Niche for stem cells can profoundly influence the position and fate of stem cells in tissue homeostasis and associated disorders, however, the mechanisms underlying the maintenance of stem cell niche remain poorly understood. Here we report that fatty acid desaturation catabolized by stearoyl-coenzyme A desaturase 1 (SCD1) regulates the activity of hair follicle stem cells (HFSCs) via blocking the formation of the bulge, a niche for HFSCs. We further unraveled that the abnormal hair growth in mice with SCD1 deletion is due to its function in K14+ basal keratinocytes rather than directly affecting HFSCs. Mechanistically, SCD1 deficiency impaired the expression of integrin α6 and the formation of hemidesmosomes (HDs), and thus allowed the activation of FAK in K14+ keratinocytes. Activated FAK subsequently stimulated PI3K and promoted the differentiation and proliferation of these keratinocytes, resulting in downward extension of the outer root sheath (ORS) and the disruption of bulge formation. Interestingly, inhibition of PI3K signaling restored bulge formation and normalized HFSCs and hair growth. Supplementation of oleic acid, the product of SCD1, to SCD1-/- mice also enhanced HD numbers, normalized the niche of HFSCs, and promoted hair growth in SCD1-/- mice. Taken together, SCD1 is indispensable for hair growth through stabilizing the number of HDs and thus sustaining bulge formation for HFSC residence and periodic activity.

overall_design: Total epidermal cells from WT and SCD1-/- mice at postnatal 1 or 21 days (P1/P21)

first: Qing


title: Identification of causal genes about osteoporosis associated with risk loci using DLO Hi-C [Hi-C]

summary: In this project, we use a simple digestion-ligation-only Hi-C (DLO Hi-C) technology, for whole-genome chromosome conformation capture, analysis of genes expression changes and transcriptional regulatory elements involved in BMMSC differentiation. Rely on GWAS data and eQTL analysis, our findings confirmed some previously reported genes that have an effect on OP, such as TIMP-2, MMP-2 and DAAM2, TMEM241 was less reported. Furthermore, our work provide a theoretical basis for the development of OP.

overall_design: The bone marrow mesenchymal stem cells (BMMSCs), osteoblasts and adipocytes

first: Zhaowei

last: Teng

first: Jin

last: Liu


title: Identification of causal genes about osteoporosis associated with risk loci using DLO Hi-C [ATAC-Seq]


title: Identification of causal genes about osteoporosis associated with risk loci using DLO Hi-C [RNA-Seq]


title: Atopic Dermatitis RNA-seq cohort

status: Public on Feb 07 2023

city: Ann Arbor

first: Lam

last: Tsoi

state: MI

address: Medical Sciences 1 Bldg. 1301 E. Catherine

institute: University of Michigan

summary: To gain a deeper understanding of the pathophysiology of AD, we conducted a large-scale transcriptomic study of AD with deeply-sequenced RNA-seq samples using long (125b) paired-end reads. By integrating deep sequencing-based skin transcriptome profiling with systems biology analysis, we are able to provide deep characterization for the expression signatures for AD.

overall_design: We performed high-depth sequencing transcriptomes obtained from a carefully matched and tightly defined cohort of AD patients, whom were recruited within an ongoing investigator-initiated clinical study to identify shared and distinct disease mechanisms of AD and Psoriasis.

first: Stephan

last: Weidinger

middle: C

first: Johann

last: Gudjonsson


title: Physiological and Molecular Characterization of an Boron-Resistant Saccharomyces cerevisiae Strain Obtained by Evolutionary Engineering

city: Istanbul

first: Halil

middle: ibrahim

last: KISAKESEN

state: Istanbul

address: ITU MOBGAM, SARIYER

department: Molecular Biology, Genetics and Biotechnology

country: Turkey

institute: Istanbul Technical University

summary: One of the essential or beneficial micronutrient for plants and animals is boron that is an ultra-trace element. Although boron can inhibit the growth of Saccharomyces cerevisiae around 80 mM, it is also a growth supplement. However, little information is currently available regarding the molecular mechanisms and essentiality of boron. In this paper, the approach was to generate S. cerevisiae mutants with high boron resistance by using evolutionary engineering strategy that was previously applied successfully. Boron-resistant S. cerevisiae mutants were obtained and their phenotypic and physiological characteristics were determined. In order to identify the molecular mechanisms implicated in boron resistance, the whole transcriptomes and genome sequence analysis of wild type and one of the most resistant mutants were compared.

overall_design: BA8 resistant Saccharomyces cerevisiae (BA8) mutant strain and reference strain were grown in yeast minimal medium. When cultures’ Optical Density (OD600) reached to about 1, which correspond to the logarithmic growth phase of the yeast cells, total RNA isolation was carried out by using RNeasy Mini Kit (Qiagen). The experiment was performed triplicates. Whole-genome microarray analysis was carried out by using Agilent DNA Microarray Technology.

first: Ulku

last: YILMAZ

first: Ceren

last: ALKIM

first: Mevlut

last: ARSLAN

middle: I

first: Zeynep

last: CAKAR


title: ASXL1 Directs Neutrophilic Differentiation via Modulation of MYC and RNA Polymerase II

city: Portland

first: Theresa

last: Lusardi

state: Oregon

address: 2720 SW Moody Avenue

department: Knight Cancer Institute

institute: OHSU

summary: Mutations in the gene Additional Sex-Combs Like 1 (ASXL1) are recurrent in myeloid malignancies as well as the pre-malignant condition clonal hematopoiesis, where they are universally associated with poor prognosis. An epigenetic regulator, ASXL1 canonically directs the deposition of H3K27me3 via the polycomb repressive complex 2. However, its precise role in myeloid lineage maturation is incompletely described. We utilized single cell RNA sequencing (scRNA-seq) on a murine model of hematopoietic-specific ASXL1 deletion and identified a specific role for ASXL1 in terminal granulocyte maturation. Terminal maturation is accompanied by down regulation of Myc expression and cell cycle exit. ASXL1 deletion leads to hyperactivation of Myc in granulocyte precursors and a quantitative decrease in neutrophil production. This failure of normal developmentally-associated Myc suppression is not accompanied by significant changes in the landscape of covalent histone modifications including H3K27me3. Examining the genome-wide localization of ASXL1 in myeloid progenitors revealed strong co-localization with RNA Polymerase II (RNAPII) at the promoters and spread across the gene bodies of transcriptionally active genes. ASXL1 deletion results in a decrease in RNAPII promoter-proximal pausing in granulocyte progenitors, indicative of a global increase in productive transcription, consistent with the known role of ASXL1 as a mediator of RNAPII pause release. These results suggest that ASXL1 inhibits productive transcription in granulocyte progenitors, identifying a new role for this epigenetic regulator and highlighting a novel possible oncogenic mechanism for ASXL1 mutations in myeloid malignancies.

overall_design: Bone marrow from ASXL1 knockout mice was analyzed by multi-omic profiling including scRNAseq, bulk RNA seq, and CUT&Tag to understand the mechanism of ASXL1 in myeloid cell production.

first: Theodore

last: Braun

first: Julia

middle: E

last: Maxson

first: Joey

last: Estabrook


title: Metformin in fetal hepatocytes

city: Aurora

first: Stephanie

last: Wesolowski

state: Colorado

address: MS F441

institute: Dr

summary: Fetal sheep hepatocytes were treated for 24h with metformin


title: Effect of Tet2 deletion on gene expression in liver macrophages in a mouse model of steatohepatitis [sorted]

first: Waihay

last: Wong

address: 360 Longwood Ave

department: Medical Oncology

institute: Dana-Farber Cancer Institute

summary: To investigate the role of hematopoietic Tet2 loss on the development of steatohepatitis, mice were transplanted with wild type or Tet2 deficient bone marrow cells and fed a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). Gene expression profiling analysis of sorted liver macrophages was performed.

overall_design: RNA-seq of liver macrophages.

first: W


title: Expression data from chordoma and notochord (microarray)

first: Stefan

last: Halvorsen

address: 185 Cambridge Street

department: Center for Computational and Integrative Biology

institute: Massachusetts General Hospital

summary:
Chordoma is a rare malignant tumor thought to originate from embryonic notochord. However, no molecular comparison of chordoma and notochord has been performed to date, leaving the identities of dysregulated pathways unclear.
Absence of a molecular description of a control tissue clouds our understanding of chordoma. Thus, we conducted an unbiased comparison of chordoma and notochord using gene expression profiling to clarify chordoma’s tissue of origin and identify novel drug targets

overall_design: RNA was extracted from fresh chordoma tumors after surgical resection using Trizol. RNA from notochord was obtained via laser capture microdissection.


title: Effect of TET2 deficient immune cells on hepatic stellate cell activation in vitro [coculture]

summary: To investigate the role of Tet2 deficient immune cells in hepatic stellate cell activation, wild type or Tet2 deficient B cells, T cells, and hepatic macrophages were isolated and co-cultured with purified hepatic stellate cells. Gene expression profiling analysis of bulk hepatic stellate cell RNA was then performed.

overall_design: RNA-seq of mouse hepatic stellate cells.


title: TXNIP loss expands Myc transcriptome

city: Salt Lake City

first: Donald

last: Ayer

state: Utah

address: 2000 Circle of Hope

department: Oncological Sciences

institute: University of Utah

summary: To examine the generality of our finding where the gene expression profile of TXNIP knockout in MDA-MB-231 cells resembles of that Myc overexpression transcriptional program, our lab has generated TXNIP null HCC70 (HCC70:TKO) and MB135 (MB135:TKO) cells. We characterized the gene exrpession programs of these cells by RNA-seq.

overall_design: TXNIP was knocked out in HCC70 and MB135 cells using CRISPR-Cas 9 method. Parental HCC70 or MB135 cells and TXNIP knockout HCC70 (HCC70:TKO) or MB135 (MB135:TKO) cells were used to perform RNA sequencing. Parental MB135 and MB135:TKO cells were differentiated for 5 days before RNA was harvested for RNA sequencing.

first: Tian-Yeh

last: Lim

first: Mallory

middle: L

last: Thomas


title: TXNIP loss


title: TXNIP loss does not increase chromatin accessibility for Myc binding.

summary: Our Myc ChIP sequencing result demonstrated that TXNIP loss increased Myc genomic occupancy levels. To determine whether TXNIP loss increased Myc genomic occupancy through increasing chromatin accessibility for Myc binding, we performed assay for transposase-accessible chromatin with sequencing (ATAC-seq) on parental 231 and 231:TKO cells.

overall_design: TXNIP was knocked out in MDA-MB-231 cells using CRISPR-Cas 9 method. Parental MDA-MB-231 (parental 231) cells and TXNIP knockout MDA-MB-231 (231:TKO) cells were used to perform ATAC-seq.

first: Megan

last: Conway

first: Katherine

last: Varley


title: Effect of hematopoietic Tet2 deletion on bulk liver gene expression in a mouse model of steatohepatitis [bulk]

middle: J

summary: To investigate the role of hematopoietic Tet2 loss on the development of steatohepatitis, mice were transplanted with wild type or Tet2 deficient bone marrow cells and fed a choline-deficient, L-amino acid-defined, high-fat diet. Gene expression profiling analysis of bulk liver RNA was then performed.

overall_design: RNA-seq of mouse livers.


title: To investigate the mechanisms of UDCA reduce inflammation effects in J774A.1 cells induced inflammation by LPS

first: Yu

last: Pi

state: Jiangsu

address: NO. 1 Weigang, Nanjing Agricultural University

institute: Nanjing Agricultural University

summary: The objective of this study was to investigate the effects of UDCA on J774A.1 cells induced inflammation by LPS. The control group treated with LPS and the UDCA group treated with both LPS and UDCA. Compared with control group, the UDCA group could reduce the inflammation effects in J774A.1 cells.

overall_design: There are two groups in this study. The control group J774A.1 treated with LPS and the UDCA group J774A.1 treated with both LPS and UDCA (n = 4).

first: Junjun

last: Wang


title: Cpeb1b-mediated cytoplasmic polyadenylation of shha mRNA modulates zebrafish definitive hematopoiesis [RNAseq_cpeb1b_ribominus]

city: Beijing

first: Bao-Fa

last: Sun

address: Da-Tun Road

institute: Beijing Institute of Genomics (BIG) of Chinese Academy of Sciences (CAS)

summary: Transcriptomics analysis of gene expression in the low dose cpeb1b MO injected wt and cpeb1b mutant zebrafish embryos

overall_design: RNA-seq of 6 samples from the low dose cpeb1b MO injected wt zebrafish embryos and 6 samples from the low dose cpeb1b MO injected Cpeb1b mutant zebrafish embryos at 8 hpf, 16 hpf, and 22 hpf.

first: J

last: Heng


title: Differential DNA Methylation Associated with Multiple Sclerosis in an Underrepresented Population  and Disease Modifying Treatments in an Underrepresented   Minority Population

city: Chicago

first: Michael

last: Carrithers

state: IL

address: 912 S Wood

department: Neurology

institute: University of Illinois

type: Methylation profiling by genome tiling array

summary: Black and Hispanic American patients frequently develop earlier onset of multiple sclerosis (MS) and a more severe disease course that can be resistant to disease modifying treatments. The objectives were to identify differential methylation of genomic DNA (gDNA) associated with disease susceptibility and treatment responses in a cohort of MS patients from underrepresented minority populations.   Patients with MS and controls with non-inflammatory neurologic conditions were consented and enrolled under an IRB-approved protocol. Approximately 64% of donors identified as Black or African American and 30% as White, Hispanic-Latino. Infinium MethylationEPIC bead arrays were utilized to measure epigenome-wide gDNA methylation of whole blood. Data were analyzed in the presence and absence of adjustments for unknown covariates in the dataset, some of which corresponded to disease modifying treatments.   Global patterns of differential methylation associated with MS were strongest for those probes that showed relative demethylation of loci with lower M values. Pathway analysis revealed unexpected associations with shigellosis and amoebiasis. Enrichment analysis revealed an over-representation of probes in enhancer regions and an under-representation in promoters. In the presence of adjustments for covariates that included disease modifying treatments, analysis revealed 10 differentially methylated regions (DMR’s) with an FDR <1E-77. Five of these genes (ARID5B, BAZ2B, RABGAP1, SFRP2, WBP1L) are associated with cancer risk and cellular differentiation and have not been previously identified in MS studies. Hierarchical cluster and multi-dimensional scaling analysis of differential DNA methylation at 147 loci within those DMR’s was sufficient to differentiate MS donors from controls.  In the absence of corrections for disease modifying treatments, differential methylation in patients treated with dimethyl fumarate was associated with immune regulatory pathways that regulate cytokine and chemokine signaling, axon guidance, and adherens junctions.   These results demonstrate possible associations of gastrointestinal pathogens and regulation of cellular differentiation with MS susceptibility in our patient cohort. This work further suggests that analyses can be performed in the presence and absence of corrections for immune therapies. Because of their high representation in our patient cohort, these results may be of specific relevance in the regulation of disease susceptibility and treatment responses in Black and Hispanic Americans.

overall_design: Whole blood methylomics, 29 multiple sclerosis samples, 18 controls

first: Jeremy

last: Bingen

first: Lindsay

last: Clark

first: Mark

last: Band

first: Ilyas

last: Muniz


title: Overcoming clinical resistance to EZH2 inhibition using rational epigenetic combination therapy

city: New York

first: Bic

last: MSKCC

state: NY

address: 1275 York Ave.

institute: Memorial SLoan-Kettering Cancer Center

summary: Recent work has revealed essential epigenetic dependencies in many cancers. Based on the functional antagonism between BAF/SWI/SNF and Polycomb repressive complex 2 chromatin remodeling in SMARCB1-deficient sarcomas, we and colleagues recently completed the clinical trial of the EZH2 inhibitor tazemetostat, leading to its FDA approval. However, the principles of response and resistance to epigenetic therapy in general and tazemetostat in particular remain unknown. Using comparative functional genomics of clinical tumor specimens and diverse experimental model systems, we have now defined molecular mechanisms of resistance to tazemetostat in epithelioid sarcomas and rhabdoid tumors. We found distinct classes of acquired mutations that converge on the RB/E2F axis and decouple EZH2 inhibition-dependent tumor cell differentiation and cell cycle control. This allows tumor cells to escape tazemetostat-induced G1 arrest, despite an active transcriptional response, and provides a general mechanism for effective EZH2 inhibitor therapy. Thus, we develop combination strategies to circumvent tazemetostat resistance by using cell cycle bypass and synthetic lethal targeting, and provide prospective biomarkers for future therapy stratification. This offers a paradigm for rational epigenetic combination therapy suitable for immediate translation to clinical trials for patients.

overall_design: We used CRISPR/Cas9 genome editing to generate biallelic RB1del G401 cells, as compared to isogenic RB1-wild type control cells produced by targeting the safe harbor locus AAVS1. We confirmed absence of RB1 protein expression in two independent clones using Western immunoblotting. Two RB1del clones were tested, termed "E1" and"F2." Cells were treated with 10µM tazemetostat or equivalent volume of DMSO for 11 days, using biological triplicates.

first: Yaniv

last: Kazansky

first: Daniel

last: Cameron

first: Phillip

last: Demarest

first: Mrinal

last: Gounder

first: Alex

last: Kentsis


title: Nizp1 is a specific NUP98-NSD1 functional interactor that regulates NUP98-NSD1-dependent oncogenic programs

city: Milan

first: Jose

middle: Manuel

last: Garcia-Manteiga

address: Via Olgettina 58

department: Center for Translational Genomics and Bioinformatics

institute: OSR - San Raffaele Scientific Institute

summary: To provide the first insight into the pathophysiological relevance of the Nizp1-NSD1 functional association, we targeted this interaction in the context of acute myeloid leukemia driven by the expression of NUP98-NSD1 oncogenic fusion. We expressed NUP98-NSD1 in mouse c-Kit+/Sca-1+/Lin- bone marrow progenitors and knocked down Nizp1 expression by shRNA. We then performed gene expression profiling analysis using data obtained from RNA-seq of 4 different cell lines.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for c-Kit+/Sca-1+/Lin- bone marrow progenitors control or expressing NUP98-NSD1 fusion and its Nizp1-KD derivatives (shNizp1#1 and shNizp1#2). Samples are run in three independent experiments

first: A

last: Berard

first: O

middle: A

last: Botrugno

first: G

last: Tonon

last: Musco


title: Cpeb1b-mediated cytoplasmic polyadenylation of shha mRNA modulates zebrafish definitive hematopoiesis [RIBO-Seq]

first: Bao-Fa

last: Sun

summary: Ribosome profiling RNA sequencing in the low dose cpeb1b MO injected wt and cpeb1b mutant zebrafish embryos

overall_design: Ribo-seq of 6 samples from the low dose cpeb1b MO injected wt zebrafish embryos and 6 samples from the low dose cpeb1b MO injected Cpeb1b mutant zebrafish embryos at 8 hpf, 16 hpf, and 22 hpf.

last: Heng


title: A prognostic signature of cell death-related genes for head and neck squamous cell carcinoma

city: Jinan

first: Xun

last: Qu

address: 107 Wenhuaxi Road

institute: Qilu Hospital of Shandong University

summary: Human papillomavirus (HPV) positive HNSCC patients generally have a favorable survival and promising responsiveness to radiotherapy, chemoradiotherapy and checkpoint blockades. However, HPV negative patients, the majority of HNSCC patients, have been largely overlooked. Cell death has been involved in the therapeutic resistance of cancers. We constructed a cell death index (CDI), based on autophagy, apoptosis and pyroptosis related genes, to predict the prognosis for HNSCC using TCGA dataset, and validated in a cohort from Qilu Hospital of Shandong University. We performed RNA sequencing of 28 paraffin-embedded tissue from HNSCC patients and determined HPV status by immunohistochemistry of p16. We found that CDI was an independent prognostic indicator for overall survival. Notably, the prognostic value of CDI was more profound in HPV negative HNSCC patients compared with those with HPV positivity.

overall_design: We constructed a cell death index (CDI), based on autophagy, apoptosis and pyroptosis related genes, to predict the prognosis for HNSCC using TCGA dataset. We performed RNA sequencing of 28 paraffin-embedded tissue from HNSCC patients diagnosed in Qilu Hospital of Shandong University and used this independent dataset for validation. We further analyzed the prognostic value of CDI in HPV positive and HPV negative subgroups.

first: Zhaodi

first: Yu

last: Dou

first: Anwei

last: Chen

first: Ketao

last: Wang

first: Jintang

first: Zhen

last: Meng

first: Markus

last: Neckenig

first: Dan

last: Ai

first: Shaohua

last: Liu

first: Zuoqing

last: Dong

first: Chao

last: Ma

first: Yufeng

last: Cheng


title: Proteomics separates diffuse high-grade gliomas in metabolic subgroups independent of 1p/19q codeletion

city: Berlin

first: Arend

last: Koch

state: Berlin

address: Charitéplatz 1

department: Dept. of Neuropathology

institute: Charité Universitätsmedizin Berlin

summary: High-grade gliomas are malignant neuroepithelial tumors. The current WHO classification for adult-type diffuse gliomas is based on IDH1/2 mutational and 1p/19q-codeletion status, which can be refined by emerging genomics, transcriptomics, and methylomics approaches. Nevertheless, therapy has been dominated by radiochemotherapy for about 15 years and progressed little in efficacy or precision through advanced molecular patient stratification. Glioma proteome alterations remain undercharacterized despite their promise for a better stratification and, in particular, the identification of therapeutic targets. Here, we used mass spectrometry (MS) to characterize 42 formalin-fixed, paraffin-embedded (FFPE) samples from IDH-wildtype (IDHwt), IDH-mutant (IDHmut) gliomas with and without 1p/19q-codeletion, and non-neoplastic brain tissue controls. Based on more than 5500 quantified proteins and 5000 phospho-sites, gliomas separated according to IDH1/2 mutational status and reflected loss of proteins encoded on 1p/19q in IDHmut, gains on chromosome 7 and losses on chromosome 10 in IDHwt. Unexpectedly, the 1p/19q-codeletion resulted in minor proteome changes. Instead, two proteomic subtypes of IDHmut gliomas showed major perturbations of mitochondrial DNA-encoded proteins, aerobic/anaerobic energy metabolism, RNA metabolism, chromatin dynamics, the extracellular matrix as well as tumor suppressor and oncoproteins. Reanalysis of three glioma proteomics studies independently validate the observed hallmarks and associate these proteomic subtypes with the well-established proneural and classic/mesenchymal IDHwt glioma subtypes. These results suggest an alternative stratification of IDHmut gliomas as part of common phenotypic subtypes independent of the IDH status, with broad therapeutic implications for patients with IDHmut gliomas in the future. Altogether, our study provides a rich protein and phospho-site resource restratifying glioma subtypes and supporting future mechanism of action and target discovery investigations.

overall_design: Bisulphite converted tumor DNA of 21 patients were hybridised to the Illumina Infinium 850k Human Methylation Beadchip

first: Jakob

last: Bader

first: Felix

last: Meissner


title: Next generation sequencing analysis of transcriptomes at different timepoints after CBL0137 treatment in SU-DHL-4, Raji and Jeko cell lines

first: Ji

last: Zhang

state: Select a State or Province

address: 197 Ruijin 2nd Road

institute: Shanghai Jiao Tong University School of Medicine

summary: To understand the mechanisms of CBL0137 in B-NHL therapy, gene expression changes of SU-DHL-4, Raji and Jeko cell lines after CBL0137 treatment were analyzed by RNA-seq

overall_design: Comparative gene expression profiling analysis of RNA-seq data for SU-DHL-4, Raji and Jeko cells treated with CBL0137 at different concentrations were sequenced.

first: Jifeng

last: Feng

first: Yan

last: Lv


title: High Sox2 expression predicts taste lineage competency of lingual progenitors in vitro

first: Linda

last: Barlow

state: CO

address: 12801 East 17th Ave

department: Cell&Dev Biology

institute: University of Colorado Anschutz Medical Campus

summary: Taste buds on the tongue are collections of taste receptor cells (TRCs) that detect sweet, sour, salty, umami and bitter stimuli. Like non-taste lingual epithelium, TRCs are renewed from basal keratinocytes, many of which express the transcription factor SOX2. Genetic lineage tracing has shown SOX2+ lingual progenitors give rise to both taste and non-taste lingual epithelium in the posterior circumvallate taste papilla (CVP) of mice. However, SOX2 is variably expressed among CVP cells suggesting that their progenitor potential may vary. Using transcriptome analysis and organoid technology, we show highly expressing SOX2+ cells are taste-competent progenitors that give rise to organoids comprising both TRCs and lingual epithelium, while organoids derived from low-expressing SOX2+ progenitors are composed entirely of non-taste cells. Hedgehog and WNT/ß-catenin are required for taste homeostasis in adult mice, but only WNT/ß-catenin promotes TRC differentiation in vitro and does so only in organoids derived from higher SOX2+ taste lineage-competent progenitors.

overall_design: Circumvallate papilla epithelial cells from 4 bins of Sox2GFP brightness were sorted using FACS and subjected to RNA-seq. Three replicates comprising of 7-13 mice per replicate were performed.

first: Shechtman

last: Lauren

first: Eric

last: Larson

first: Barlow

last: Linda


title: TXNIP loss increases Myc genomic occupancy [ChIP-seq]

first: Donald

last: Ayer

summary: Our RNA sequencing result demonstrated that TXNIP loss increased the levels of Myc-dependent transcription. To determine whether TXNIP regulates global Myc genomic occupancy, we performed Myc ChIP-seq on parental 231 and 231:TKO cells.

overall_design: TXNIP was knocked out in MDA-MB-231 cells using CRISPR-Cas 9 method. Parental MDA-MB-231 (parental 231) cells and TXNIP knockout MDA-MB-231 (TKO) cells were used to perform Myc ChIP sequencing.

first: Tian-Yeh

last: Lim


title: Gene expression profiles of mouse ischemia-reperfusion liver zones with or without celastrol-treated.

first: Jiaqi

last: Xin

address: No.11 Xitoutiao outside You’anmen

institute: CCMU

summary: Hepatic ischemia-reperfusion (I/R) has long affected the success rate of liver transplant. Though zone-specific injury induced by I/R was observed, elaborated cellular and molecular mechanisms underlying the I/R injury pattern have not been revealed. Spatial transcriptomics analysis has great potential to uncover the mechanisms of liver I/R injury.

overall_design: We evaluated the gene expression profile of different zones of mouse liver from sham group, 70% liver I/R group and celastrol-treated I/R group using DSP spatial transcriptomics analysis. 147 ROIs were sequenced totally.

first: Ting

last: Yang

first: Xiaoyi

last: Wu

first: Yingting

first: Yi

first: Xuan

first: Mengxi

last: Jiang

first: Wei

last: Gao


title: Determination of the genome wide binding pattern of TLE3 in luminal breast cancer

city: Cleveland

first: Ruth

last: Keri

state: OHIO

address: 9500 Euclid Ave

institute: Cleveland Clinic

summary: The identification of mechanisms controlling breast tumor progression from less aggressive to highly metastatic disease should provide novel therapeutic targets for patients. Here we report the transcriptional corepressor, TLE3, as a critical regulator of cellular plasticity in breast cancer. TLE3 facilitates repression of genes associated with the highly aggressive basal-like breast cancer (BLBC) subtype within luminal cells. Additionally, maintenance of the luminal lineage is dependent on appropriate localization of TLE3 to its transcriptional targets which is mediated through interaction with FOXA1. Furthermore, the ability of TLE3 to repress BLBC transcription results in reduced metastatic capacity and aggressive cellular behaviors. Together our findings establish TLE3 as a critical transcriptional mediator of breast cancer aggressiveness, with TLE3 sustaining the more differentiated and less metastatic nature of luminal tumors through suppression of gene expression programs associated with BLBC.

overall_design: We performed Chip-seq to determine genome wide binding pattens of TLE3 in the luminal breast cancer cell lines, MDA-MB-453. SKBR3, and T47D. Additionally, we performed ChIP-seq for the transcription factor, FOXA1 in these cell lines and determine the extent of TLE3/FOXA1 co-binding in luminal breast cancer.

first: Lindsey

last: Anstine


title: SlWRKY33 confers cold tolerance through activation of various downstream signaling pathways in cultivated tomato

city: 杭州市

first: Mingyue

last: Guo

state: 浙江省

address: 浙江大学紫金港校区

institute: 浙江大学

summary: To determine which genes were directly regulated by SlWRKY33 under cold stress, we performed ChIP-seq of SlWRKY33-OE plants with and without cold treatment.

overall_design: We performed ChIP-seq of SlWRKY33-OE plants with and without cold treatment.

first: Fengjun

first: Chenxu

last: Liu

first: Jie

last: Zhou


title: Expression data from chordoma and notochord (RNA-Seq)

city: Boston

first: Stefan

last: Halvorsen

state: MA

summary: Chordoma is a rare malignant tumor thought to originate from embryonic notochord. However, no molecular comparison of chordoma and notochord has been performed to date, leaving the identities of dysregulated pathways unclear. Absence of a molecular description of a control tissue clouds our understanding of chordoma. Thus, we conducted an unbiased comparison of chordoma and notochord using gene expression profiling to clarify chordoma’s tissue of origin and identify novel drug targets

overall_design: RNA was extracted from fresh chordoma tumors after surgical resection using Trizol. RNA from notochord was obtained via laser capture microdissection.


title: TXNIP loss expands Myc transcriptome [RNA-seq]

first: Donald

summary: To better understand how TXNIP in the contributes to the poor prognosis of triple-negative breast cancers, our lab has generated TXNIP null MDA-MB-231 cells (231:TKO). We characterized the gene exrpession programs of these cells by RNA-seq. To determine the Myc-dependence of the transcriptional programs of 231:TKO cells, we used an siRNA RNA approach to reduce Myc levels.

overall_design: TXNIP was knocked out in MDA-MB-231 cells using CRISPR-Cas 9 method. Parental 231 cells and TXNIP knockout MDA-MB-231 (231:TKO) cells were used to perform RNA sequencing. Parental MDA-MB-231 (parental 231) and TXNIP knockout MDA-MB-231 (TKO) cells were treated with either siRNA non-targeting or siRNA Myc for 48 hours to knock down Myc prior harvesting for RNA sequencing.

first: Blake

last: Wilde


title: TLE3 drives luminal identity of breast cancer through transcriptional repression of FOXA1-target genes

overall_design: To determine the TLE3-regulated transcriptome in luminal breast cancer cells, transient silencing of TLE3 was carried out using siRNAs targeting TLE3 (siTLE3), FOXA1 (siFOXA1), or a non-silencing control (siNS) in T47D, MDA-MB-453, and SKBR3 breast cancer cell lines. At 48 hours post-transfection, RNA was collected and prepared for sequencing. RNA-seq was performed on three replicates for each experimental condition.


title: Short-term hypergravity effects on Jurkat T cells

city: Zurich

first: Cora

middle: S.

last: Thiel

address: Winterthurerstrasse 190

department: Institute of Anatomy

institute: University of Zurich

summary: Jurkat T cells have been exposed to 9g hypergravity in a custom-built pipette centrifuge for different times (GBF2021). Additionally, Jurkat T cells have been exposed to 300g for 5 minutes in a standard benchtop centrifuge, and waited for different times until adding lysis buffer. For comparison, Jurkat T cells have been exposed to 5 minutes of 42°C.

overall_design: 6x Control 15 minutes in pipette (Ctrl), 6x Control 60 minutes in pipette (Ctrl60), 6x incubation in pipette centrifuge for 20s/75s/3min/5min/7min/9min/15min/60min (hypg020s/hypg075s/hypg5/hypg7/hypg9/hypg15/hypg60), 4x 300g 5 minute centrifugation waiting for 1min/4min/15min until adding lysis buffer, 4x control to the 300g samples, 4x heat shock 42°C

first: Thiel

last: Cora

first: Vahlensieck

last: Christian

first: Oliver

last: Ullrich


title: Enhancer remodeling drives MLL oncogene-dependent transcriptional dysregulation in leukemia stem cells

city: Stanford

first: Feng

last: Pan

state: CA

address: 265 Campus Drive

department: Pathology

institute: Stanford University School of Medicine

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

overall_design: Refer to individual Series


title: CircRNA expression profiles and functional analysis in a mouse model of chronic intermittent hypoxia-induced renal injury

city: 泉州

first: 清石

last: 陈

state: 福建省

address: 福建省泉州市鲤城区中山北路34号

institute: 医科大学附属第二医院

summary: The aim of this current study is to identify the global changes of circRNAs expression in OSA-induced renal damage.

overall_design: The mouse model of OSA treated by chronic intermittent hypoxia (CIH) was established. We assessed the expression profiles of circRNAs by microarray analysis.

first: Qingshi

last: Chen


title: Expression data from chordoma and notochord

institute: Massachusetts General Hospital


title: Enhancer remodeling drives MLL oncogene-dependent transcriptional dysregulation in leukemia stem cells [ChIP-seq]

summary: Acute myeloid leukemia (AML) with MLL gene rearrangement (MLLr) comprises a cellular hierarchy in which subpopulations of cells with distinct immunophenotypes serve as functional leukemia stem cells (LSCs, c-Kit+) and mature AML cells (mAML, c-Kit-), respectively. They are maintained by a unique gene expression program and chromatin states, which are thought to reflect the actions of cis-regulatory elements with features of enhancers. Here, we delineate the active enhancer landscape and observe pervasive enhancer malfunction in MLLr LSCs. Reconstruction of regulatory networks revealed a master set of hematopoietic transcription factors (TFs). We show that EP300 is an essential transcriptional coregulator with these TFs for maintaining LSC oncogenic potential, as it controls essential gene expression through modulation of H3K27 acetylation and assessments of transcription factor dependencies. Moreover, the EP300 small molecule inhibitor A-485 affects LSC growth by targeting enhancer activity via histone acetyltransferase domain inhibition. Together, these data implicate a perturbed MLLr-specific enhancer accessibility landscape, suggesting the possibility for disruption of the LSC enhancer regulatory axis as a promising therapeutic strategy in AML.

overall_design: Examination of 3 different histone modifications in GMP, LSC, and mAML. Also examination of H3K27ac and P300 in LSC after A-485 treatment.


title: Self-renewing macrophages in dorsal root ganglia contribute to promote nerve regeneration

city: St. Louis

first: Rui

last: Feng

state: Missouri

address: 660 South Euclid Avenue

institute: Washington University in St louis

summary: Primary sensory neurons with cell soma in dorsal root ganglia (DRG) project axons in both the peripheral nervous system and the spinal cord. Whereas the peripheral axon can regenerate after injury, the central axon cannot, providing an opportunity to identify the mechanisms that promote axon regeneration. Using this system, multiple intrinsic mechanisms operating in sensory neurons have been shown to promote axon regeneration. Peripheral sensory neurons also benefit from a supportive environment. In particular, macrophages play important roles in nerve regeneration by clearing debris and regulating Schwann cell function at the site of injury in the nerve. Nerve macrophages have been characterized at the molecular level and derive for the most part from infiltrating monocytes. However, the role and origin of macrophages in the DRG remains poorly understood. Following a 14-days treatment with a CSF1R inhibitor, less than 10% of macrophages remained in the DRG. Recovery from this treatment resulted in a dramatic macrophage repopulation, with the number of DRG macrophages reaching level similar to untreated mice three days post injury. These repopulated DRG macrophages contribute to promote axon regeneration. Our scRNA-seq analysis allow in-depth characterization of the repopulated DRG macrophages in response to nerve injury. These data will provide a better understanding of DRG macrophages and the molecular mechanisms by which they contribute to peripheral nerve repair. These studies may lead to new potential targets to promote axon regeneration.

overall_design: We have applied the high-throughput single-cell mRNA sequencing technique, using the Chromium Single Cell Gene Expression Solution (10x Genomics) to mouse L4-L5 DRG in repopulated macrophages with/without injured conditions (3 days post sciatic nerve crush injury), 2 biological replicates for each sample.

first: Valeria

last: Cavalli


title: RIP-seq for Cpeb1b in zebrafish embryos

first: Bao-Fa

last: Sun

summary: Cpeb1b-mediated cytoplasmic polyadenylation modulates hematopoietic stem and progenitor cell development via translational control

overall_design: RIP-seq of 2 samples from Flag-cpeb1b mRNA injected zebrafish embryos at 16 hpf including two biological replicates

first: J

last: Heng


title: A specific molecular signature in SARS-CoV-2 infected kidney biopsies

city: Paris

first: Pierre

last: Isnard

address: 156-160, rue de Vaugirard

institute: INEM

summary:
To characterize the pathophysiology of kidney injury in a large kidney biopsy series of living SARS-CoV-2–infected patients
RNA-seq was performed to compare transcriptional changes in damaged kidneys of COVID-19 patients to those of healthy, non-COVID-19 injured kidneys and Hantavirus injured kidney

overall_design: Comparative gene expression profiling analysis of RNA-seq data for kidney samples of COVID-19 patients to those of healthy, non-COVID-19 injured kidneys and Hantavirus injured kidneys

first: Paul

last: Vergnaud

first: Matthieu

last: Jamme

first: Serge

last: Garbay

first: Alexandre

last: Karras

first: Dany

last: Anglicheau

first: Valérie

last: Galantine

first: Arwa

last: Eddine

first: Clément

last: Gosset

first: Frank

last: Pourcine

first: Mohammed

last: Zarhrate

first: Jean-Baptiste

last: Gibier

first: Marco

last: Pontoglio

first: Fabiola

last: Terzi

first: Marion

last: Rabant


title: We performed ChIP-seq for TLE3 in MDA-MB-453 cells with and without FOXA1 transient silencing (siFOXA1 vs siNS) to determine the requirement of FOXA1 for TLE3 binding.

first: Ruth

last: Keri

overall_design: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for TLE3 in the MDA-MB-453 breast cancer cell line.

first: Lindsey

last: Anstine


title: Enhancer remodeling drives MLL oncogene-dependent transcriptional dysregulation in leukemia stem cells [RNA-seq]

first: Feng

last: Pan

overall_design: mRNA profiles of GMP, LSC, and mAML. mRNA profiles of LSCs treated with A-485 at different time points


title: Transgenerational inheritance of epigenetic signatures at CpG islands in mice

city: La Jolla

first: Yuta

last: Takahashi

address: 10010 N Tottey Pines Rd

institute: Salk Institute

type: Methylation profiling by high throughput sequencing

summary: Transgenerational epigenetic inheritance in mammals remains a subject of debate. Here we demonstrate that DNA methylation of promoter-associated CpG islands (CGIs) can be transmitted from parents to their offspring in mice. We generated DNA methylation-edited mouse embryonic stem cells (ESCs) in which CGIs of two metabolism related genes, the Ankyrin repeat domain 26 and the low-density lipoprotein receptor, were specifically methylated and silenced. DNA methylation-edited mice generated by microinjection of the methylated ESCs exhibited abnormal metabolic phenotypes. Both the acquired methylation of the targeted CGI and the phenotypic traits were maintained and transmitted across multiple generations. The heritable CGI methylation was subjected to reprograming in parental PGCs and subsequently reestablished in the next generation at post-implantation stages. These observations provide a first concrete step in support of transgenerational epigenetic inheritance in mammals, which may allow for a better understanding of the etiology, diagnosis and prevention of non-genetically inherited human diseases.

overall_design: Target enrichment-genome bisulfite sequencing (TEBS), Whole genome sequencing (WGS), Whole genome bisulfite sequencing (WGBS)

first: Mariana

last: Morales Valencia

first: Yang

last: Yu

first: Yasuo

last: Ouchi

first: Kazuki

first: Maxim

last: Nikolaievich Shokhirev

first: Kathryn

last: Lande

first: April

last: Williams

first: Chiara

last: Fresia

first: Masakazu

last: Kurita

first: Tomoaki

last: Hishida

first: Kensaku

last: Shojima

first: Fumiyuki

last: Hatanaka

first: Estrella

last: Nuñez-Delicado

first: Concepcion

last: Rodriguez Esteban

first: Juan Carlos

last: Izpisua Belmonte


title: Production of rAAV by plasmid transfection induces antiviral and inflammatory responses in suspension HEK293

status: Public on Feb 06 2023

city: Morrisville

first: Cheng-Han

last: Chung

address: 7030 Kit Creek Rd

institute: Pfizer Inc.

summary: To understand the response of host cells to rAAV vector production via plasmid transfection, samples were collected throughout the course of three 50 L production batches and analyzed by bulk RNA sequencing of polyadenylated transcripts (RNA-seq). Gene ontology analysis determined that upregulated pathways included inflammatory and antiviral responses. Systematic analyses of the cellular transcriptional response to rAAV production indicates that these host cells are not passively supporting vector manufacture, and therefore may illuminate genes and pathways that influence rAAV production, thereby enabling the rational design of next-generation manufacturing platforms to support safe, effective, and affordable AAV-based gene therapies.

overall_design: Samples were collected immediately prior to transfection (0 h) and at 3, 6, 12, 24, 36, 48, and 72 hours post transfection (hpt).

first: Christopher

last: Murphy

first: Douglas

last: McCarty

first: Joseph

last: Rabinowitz

first: Reiko

last: Nakashima

first: Vincent

middle: P

last: Wingate

first: Wei

last: Wei

first: Jeffrey

middle: W

last: Pavlicek

first: Erik

middle: S

last: Barton


title: Accumulation of branched-chain amino acids reprograms glucose metabolism in CD8+ T cells with enhanced effector function and anti-tumor responses

city: Shanghai

first: Chengcheng

last: Yao

address: 280 South Chongqing Road, Shanghai, China

institute: Shanghai Jiaotong University School of Medicine

summary: Branched-chain amino acids (BCAAs) provide nutrient signals for cell survival and growth. How BCAAs affecting CD8+ T cell functions remains unexplored. Herein we reported that accumulation of BCAAs in CD8+ T cells due to the impairment of BCAA degradation in 2C-type serine/threonine protein phosphatase (PP2Cm) deficient mice leads to hyper-activity of CD8+ T cells and enhanced anti-tumor immunity. CD8+ T cells from PP2Cm-/- mice upregulate glucose transporter Glut1 expression in a FoxO1-dependent manner with more glucose uptake as well as increased glycolysis and oxidative phosphorylation. Moreover, BCAA supplementation recapitulates CD8+ T cell hyper-functions and synergizes with anti-PD-1, supported by a better prognosis in NSCLC patients harboring high BCAAs when receiving anti-PD-1 therapy. Our finding thus reveals that accumulation of BCAAs promotes effector function and anti-tumor immunity of CD8+ T cells through reprogramming glucose metabolism, making BCAAs alternative supplementary components to increase the clinical efficacy of anti-PD-1 immunotherapy against tumors.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for CD8+T cells  from PP2Cm KO mice and CD8+T cells from WT mice.

first: Cheng-cheng

first: Rui-ming

last: Sun

first: Yi

last: Yang

first: Hai-yan

last: Zhou

first: Zhou-wenli

last: Meng

first: Rui

last: Chi

first: Li-liang

last: Xia

first: Ping

last: Ji

first: Ying-ying

last: Chen

first: Guo-qing

last: Zhang

first: Hai-peng

first: Shun

last: Lu

first: Chen

first: Ying

last: Wang


title: Developmental spatial transcriptome for the molecular annotation of germ layer formation and the acquisition of tissue lineage attributes of post-implantation mouse embryo

city: Guangzhou

first: Guangdun

last: Peng

address: 190 Kaiyuan Road

department: Guangzhou Institutes of Biomedicine and Health

institute: Chinese Academy of Sciences

summary: The blueprint of embryonic development is first visualized in the context of regionalization of cell fates of germ layer tissues in the post-implantation mouse embryo. Knowledge of the genetic and signaling activities that underpin gastrulation, lineage specification and tissue patterning has been gleaned from embryological experimentation and phenotypic analysis of loss- and gain-of-function genetic models. However, a comprehensive genome-wide molecular annotation of the mechanism of gastrulation has yet to be undertaken. Here, we reported the findings of a transcriptome study of cell populations at defined positions in the epiblast, ectoderm, mesoderm and endoderm of the pre-gastrulation and gastrulation stage embryos. This developmental and spatial transcriptome has defined the genealogy of sub-populations of cells in the germ layers. The transcriptome further identifies the molecular determinants such as the transcriptional factors and epigenetic entities, and the activity of signaling pathway and the transcriptional networks that drive the lineage commitment of the pluripotent epiblast cells and the germ layer precursors.

overall_design: By using spatial transcriptome of Geo-seq, we carried out transcriptome profiling on embryo sections at a high resolution of ~20 cells per sample. We then constructed a comprehensive spatial transcriptome map from the pre-gastrulation to late-gastrulation embryos that are visualized in a 3D embryonic model based on the sequencing data.

first: Guizhong

last: Cui

first: Shengbao

last: Suo

first: Naihe

last: Jing

first: Jing-Dong

last: Han


title: Role of RelB in Interferon Dependent and Indpendent Gene Regulation

city: Los Angeles

first: Hector

last: Navarro

state: California

address: 570 Boyer Hall

department: MIMG

institute: UCLA

summary: To investigate the Gene dysregulation caused by loss of RelB and identify candidate genes driving the loss of RelB autoimmune phenotype

overall_design: Comparative gene expression profiling analysis of RNA-seq data for bone marrow derived dendritic cells from WT, RelBko, IFNARko, and IFNARko;RelBko Mice

first: Navarro

last: Hector

first: Alexander

last: Hoffmann


title: cAMP/PKA signaling promotes AKT deactivation via reducing CIP2A expression, thereby facilitating decidualization

city: Shenzhen

first: Weijie

last: Zhao

address: Zhenyuan Road

institute: Reproductive Medicine Center, The Seventh Affiliated Hospital, Sun Yat-sen University

summary: Decidualization is a progesterone-initiated differentiation concerning the endometrium and is dedicated to supporting the placenta and embryo development. During the process, cAMP signaling is widely known to be indispensable, but the details are not fully understood. In this study, we show that cAMP signaling promotes AKT deactivation in endometrial stromal cells, which favors their decidualization. The deactivation of AKT is found to be a consequence of the reduced expression of several inhibitors of PP2A, the major phosphatase of AKT, with CIP2A being the most prominent. To show that CIP2A loss is obligatory for decidualization, we performed this ATAC-seq analysis. Persistent CIP2A expression impairs the chromatin accesibility remodeling during decidualization.

overall_design: Primary endometrial stromal cells (ESC) were transfected with lentivirus, subjected to puromycin selection, and afterwards treated with progesterone (P4) and db-cAMP for 48 h as follows: (1) vector, DMSO; (2) vector, P4/db-cAMP; (3) ovCIP2A, P4/db-cAMP

first: Chunfang

last: Xu

first: Lijin

first: Lin

last: Ma

first: Meirong

last: Du


title: Effect of hematopoietic Tet2 deletion on steatohepatitis

first: Waihay

last: Wong

address: 360 Longwood Ave

institute: Dana-Farber Cancer Institute


title: Next Generation Sequencing of Transcriptomic microRNAs from Murine Articular Chondrocytes Treated with IL-1𝝱

city: St Louis

first: Jie

last: Shen

state: MO

address: 425 S. Euclid Ave

institute: Washington University in St Louis