title: Glomerular endothelial cell and podocyte stresses as well as crosstalk in structurally normal kidney transplants

status: Public on Dec 23 2021

city: Ann Arbor

first: Rajasree

last: Menon

state: Michigan

address: 4544E, MSRB2, Catherine Street, University of Michigan

department: Department of Computational  Medicine and Bioinformatics

institute: University of Michigan

summary: Even among apparently healthy human allografts with no detectable histologic abnormality, transcriptomic changes reflecting cell stresses have already been set in motion that could drive hypertrophy-associated glomerular disease progression

overall_design:
Cell-specific transcriptional profiles of GECs and podocytes of 1st-year surveillance biopsies (n=14) with normal histology from low immune risk recipients with no post-transplant complications were compared to healthy living donor controls (n=20) in an observational study
***note from submitter: The raw data which includes patient sequencing data cannot be uploaded now due to IRB restrictions.***

first: Abhijit

last: Naik

first: Edgar

last: Otto

first: Matthias

last: Kretzler


title: Gene expression profiles in rat alveolar macrophages exposure to submicron carbon fibers

status: Public on Sep 10 2021

city: Tsukuba

first: Katsuhide

last: Fujita

address: 16-1 Onogawa

department: Research Institute of Science for Safety and Sustainability

country: Japan

institute: National Institute of Advanced Industrial Science and Technology

summary: To evaluate the biological effects at the transcriptional level of manufactured nanomaterials, whole genome microarrays of rat alveolar macrophages (NR8383) exposed to three types of submicron-diameter carbon fibers (SCFs) with different physicochemical properties were performed. In comparison with the fibers of SCF1, the fibers of SCF2 were shorter, and the fibers of SCF3 were thinner.

overall_design: Rat alveolar macrophages (NR8383) were exposed to 10 µg/mL of three kinds of SCFs (SCF1, SCF2, and SCF3) for 24 hours, respectively. The experiments were performed using vehicle control  (n=4). Cyanine-3-labeled cRNA prepared from NR8383 exposure to SCFs was hybridized to a Whole Rat Genome Microarray. The scanned images of hybridized microarray slides were analyzed numerically to evaluate the biological effects at the transcriptional level of SCFs on NR8383.

first: Sawae

last: Obara


title: Transcriptomics of skin reveal potential molecular mechanisms of psoriasis

status: Public on Dec 17 2021

city: Nanjing

first: Dijun

last: Chen

state: Jiangsu

address: Xianlin

department: Life Sciences

country: China

institute: Nanjing University

type: Expression profiling by high throughput sequencing

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: Developmental single-cell transcriptomics in the Lytechinus variegatus sea urchin embryo

status: Public on Sep 24 2021

city: Durham

first: David

middle: R

last: McClay

address: 124 Science Drive room 4115

department: Biology

country: USA

institute: Duke University

summary: Using scRNA-seq coupled with computational approaches, we studied transcriptional changes in cell states of sea urchin embryos during development to the larval stage. Eighteen closely spaced time points were taken during the first 24 hours of development of Lytechinus variegatus (Lv). Developmental trajectories were constructed using Waddington-OT, a computational approach to "stitch" together developmental timepoints. Skeletogenic and primordial germ cell trajectories diverged early in cleavage. Ectodermal progenitors were distinct from other lineages by sixth cleavage, though a small percentage of ectoderm cells briefly co-expressed endoderm markers indicating an early ecto-endoderm cell state, likely in cells originating from the equatorial region of the egg. Endomesoderm cells originated at 6th cleavage also and this state persisted for more than two cleavages, then diverged into distinct endoderm and mesoderm fates asynchronously, with some cells retaining an intermediate specification status until gastrulation. 79 of 80 genes (99%) examined, and included in published developmental gene regulatory networks (dGRNs), are present in the Lv-scRNA-seq dataset, and expressed in the correct lineages in which the dGRN circuits operate.

overall_design: 19 scRNA-seq samples, with 1 replicate capturing 18 time points over 24 hours of sea urchin development

first: Abdull

middle: J

last: Massri

first: Laura

last: Greenstreet

first: Anton

last: Afanassiev

first: Alejandro

last: Berrio

first: Greg

middle: A

last: Wray

first: Geoffrey

last: Schiebinger


title: Sex-biased ZRSR2 mutations in myeloid malignancies impair plasmacytoid dendritic cell activation and apoptosis

status: Public on Oct 15 2021

city: Boston

first: Andrew

last: Lane

state: MA

address: 450 Brookline Ave

institute: Dana-Farber Cancer Institute


title: Global mapping of the energetic and allosteric landscapes of protein binding domains

status: Public on Sep 13 2021

city: New York

first: Julia

last: Domingo

state: NY

address: 101 6th Av

institute: New York Genome Center

summary: Allosteric communication between distant sites in proteins is central to nearly all biological regulation but still poorly characterised for most proteins, limiting conceptual understanding, biological engineering and allosteric drug development. Typically only a few allosteric sites are known in model proteins, but theoretical, evolutionary and some experimental studies suggest they may be much more widely distributed. An important reason why allostery remains poorly characterised is the lack of methods to systematically quantify long-range communication in diverse proteins. Here we address this shortcoming by developing a method that uses deep mutational scanning to comprehensively map the allosteric landscapes of protein interaction domains. The key concept of the approach is the use of ‘multidimensional mutagenesis’: mutational effects are quantified for multiple molecular phenotypes—here binding and protein abundance—and in multiple genetic backgrounds. This is an efficient experimental design that allows the underlying causal biophysical effects of mutations to be accurately inferred en masse by fitting thermodynamic models using neural networks. We apply the approach to two of the most common human protein interaction domains, an SH3 domain and a PDZ domain, to produce the first global atlases of allosteric mutations for any proteins. Allosteric mutations are widely dispersed with extensive long-range tuning of binding affinity and a large mutational target space of network-altering ‘edgetic’ variants. Mutations are more likely to be allosteric closer to binding interfaces, at Glycines in secondary structure elements and at particular sites including a chain of residues connecting to an opposite surface in the PDZ domain. This general approach of quantifying mutational effects for multiple molecular phenotypes and in multiple genetic backgrounds should allow the energetic and allosteric landscapes of many proteins to be rapidly and comprehensively mapped.

overall_design: DNA-seq of PCR amplicon

first: Andre

last: Faure

first: Júlia

first: Jörn

middle: M

last: Schmiedel

first: Cristina

last: Hidalgo-Carcedo

first: Guillaume

last: Diss

first: Ben

last: Lehner


title: Transcriptomics profiling of white adipose tissue of wildtype (WT) mice fed a normal chow diet (NCD) or high-fat diet (HFD)

status: Public on Aug 30 2021

city: Seoul

first: Yoon

middle: Keun

last: Cho

address: 1, Gwanak-ro Bldg 20-417, Gwanak-gu

country: South Korea

institute: Seoul National University

summary: Adipose tissue is a crucial metabolic organ maintaining energy homeostasis via catabolic and anabolic metabolism. As high-fat diet feeding leads to metabolic dysfunction, here, we aimed to study the effect of 8 weeks of high-fat diet feeding on WT mice and compare genes differentially regulated depending on the type of diets intaking.

overall_design: White adipose tissue mRNA profiles of WT mice fed a NCD or HFD were generated by deep sequencing. Three biological replicates were analyzed for each of two conditions.

first: Yun

middle: H

last: Lee

middle: K


title: Natural variation in activation of KAI2/HTL pathway promotes germination in the dark in Arabidopsis

status: Public on Sep 01 2021

city: Toronto

first: Zhenhua

last: Xu

state: ON

address: 25 Willcocks St.

department: Cell and Systems Biology

country: Canada

institute: University of Toronto

summary: Elucidating direct roles of natural variation in biological processes has been challenging due to the difficulty in dissecting the causal role of a gene in traits displaying continuous variation. The decision of a seed to germinate is an easily quantifiable binary choice, which makes it an ideal phenotype to assess the contribution of natural variation in adaptation of plants to begin their lifecycle under optimal conditions. seeds must integrate a complex array of environmental signals to begin their lifecycle under optimal conditions. Light availability is a crucial environmental stimulus that promotes germination in many small seed plant species including Arabidopsis thaliana. Upon perception of light by photoreceptors, phytohormones act as internal signals to coordinate germination but the karrikin (KAR) signalling pathway through the HTL/KAI2 receptor is thought to play a rudimentary role in Arabidopsis germination (REF). Here we show that the AtHTL/KAI2 pathway is required and sufficient to promote germination under low light conditions. Activation of the AtHTL/KAI2 receptor by nanomolar Karrikin2 (KAR2) concentrations or inactivation of SMAX1 bypass the light requirement for germination. By performing a screen of A. thaliana accessions that can germinate under low light conditions, we identified an accession from Afghanistan (Ara-1) which misexpressed AtKAI2/HTL and had a nearly identical transcriptional signature to the activation of AtKAI2 upon addition of KAR2 in the reference accession. Our data suggest that AtKAI2 is a central regulator of germination in natural Arabidopsis populations in response to light availability, to optimize germination timing in their ecological niche.

overall_design: Examined the transcriptome profile of dark germinating (24h germination in dark after dark imbibition) Arabidopsis thaliana seeds from Ara-1 accession wild-type and AtKAI2 overexpression lines in Col-0 accession with different Karrikin2 (KAR2) treatment.

first: Gianni

last: Pescetto

first: Michael

last: Bunsick

first: Christopher

middle: S

last: McErlean

first: Shelley

last: Lumba


title: Wound healing and hair follicle regeneration with topical BRAF inhibitor therapy in a diabetic model

status: Public on May 22 2021

city: Los Angeles

first: Willy

last: Hugo

state: California

address: 10833 Le Conte Ave

department: Medicine

institute: University of California, Los Angeles

summary: Wound healing is a multi-step process to rapidly restore barrier function. This process is often impaired in diabetic patients resulting in chronic wounds and amputation. We previously found that paradoxical activation of the mitogen-activated protein kinase (MAPK) pathway via topical administration of the BRAF inhibitor vemurafenib accelerates wound healing by activating keratinocyte proliferation and reepithelialization pathways in healthy mice. Herein, we investigated whether this wound healing acceleration also occurs in impaired diabetic wounds and found that topical vemurafenib not only improves wound healing in a murine diabetic wound model, but unexpectedly promotes hair follicle regeneration. Neogenic hair follicles expressing Sox-9, CD34 and K15 were found in wounds of diabetic and non-diabetic mice, and their formation can be prevented by blocking downstream MEK signaling. Thus, topically applied BRAF inhibitors may accelerate wound healing, and promote the restoration of improved skin architecture in both normal and impaired wounds.

overall_design: The effect of vemurafenib vs. vehicle control treatment on the wound healing of diabetic model mice after 16 days

first: Helena

last: Escuin-Ordinas

first: Yining

last: Liu

first: Lu

last: Sun

first: Robert

last: Dimatteo

first: Rong

last: Huang

first: Paige

last: Krystofinski

first: Ariel

last: Azhdam

first: Jordan

first: Begoña

last: Comin-Anduix

first: Alistair

last: Cochran

first: Roger

last: Lo

first: Tatiana

last: Segura

first: Philip

middle: O

last: Scumpia

first: Antoni

last: Ribas


title: The CovR regulatory network drives the evolution of Group B Streptococcus virulence

status: Public on Aug 23 2021

city: Paris

first: Rachel

last: Legendre

address: 28, rue du docteur Roux

department: Research and Resource Center for Scientific Informatics

country: France

institute: Institut Pasteur

type: Genome binding/occupancy profiling by high throughput sequencing


title: RNA sequencing of human airway epithelial cultures from cystic fibrosis (CF) and non-CF donors exposed to tumor necrosis factor-alpha and interleukin-17 (TNFα+IL-17) for 48 hours

status: Public on Jun 30 2021

city: Iowa City

first: Alejandro

middle: A.

last: Pezzulo

state: Iowa

address: 6316 Pappajohn Biomedical Discovery Building

department: Department of Internal Medicine

institute: Universty of Iowa

summary: Gene expression was compared between disease conditions (CF vs. non-CF) and treatments (TNFα+IL-17 vs. control) as well as the interaction between disease and treatment.

overall_design: Primary differentiated airway epithelia were treated with TNFα (10ng/ml) and IL-17 (20ng/ml) for 48 hours, prepared for RNA sequencing, and sequenced on Illumina HiSeq 4000 system using 2x150bp paired end SBS chemistry.

first: Tayyab

last: Rehman

first: Andrew

middle: L

last: Thurman

first: Michael

last: Welsh


title: ChIP-seq of the response regulator CovR in Group B Streptococcus (GBS)

summary: We report the characterization of the major regulator of virulence gene expression (CovR) in Group B Streptococcus. The ChIP-seq experiments define the binding of CovR on the chromosome of the BM110 strain, a representative of the hypervirulent GBS lineage responsible of neonatal meningitis. Regulatory evolution of CovR signaling was investigated by comparing ChIP-seq done in parallel in a second GBS clinical isolate (NEM316) not belonging to the hypervirulent lineage.

overall_design: In order to define the CovR binding regions along the genome of the GBS, we expressed an ectopic flagged variant of CovR (CovR-3XFLAG) under the control of a anhydrotetracycline (aTc) inducible promoter in a ∆covR background. This functional FLAG-CovR variant was used for ChIP-sequencing with immunoprecipitations done on exponentially growing bacteria in THY + Hepes 50 mM. Two independent  replicates were done for each sample (Rep1 and Rep2). CovR-FLAG were induced with 50 and 200 ng/ml aTc in the cultures. The controls are the non-induced condition (no-aTc) and the non-epitope tagged CovR strain (no-TAG). Experiments were done in the BM110 and NEM316 strains.

first: Maria

middle: V

last: Mazzuoli

first: Maëlle

last: Daunesse

first: Claudia

last: Chica

first: Arnaud

last: Firon


title: Transcriptomic analysis of the major regulator of virulence CovR in Group B Streptococcus strains BM110 and NEM16.

summary: To define the transcriptional response associated to a CovR inactivation we performed RNA-Seq in GBS strains BM110 and NEM316. We used mutants in which CovR is  inactivated following  a two base-pairs chromosomal substitution (AT->CC) resulting in the translation of a CovRD53A variant unable to be phosphorylated by the histidine kinase CovS. We also used a ∆covR mutant in strain BM110 in which the covR sequence is deleted from the chromosome.

overall_design: We have perfomed two experiments. Th first experiment includes  the transcriptomes of BM110 and NEM316 wild-type and the correspondent CovRD53A mutant strains, whom cultures, RNA preparation and sequencing were done in parallel to allow a quantitative comparison. The second experiment includes  the transcriptomes of BM110 wild-type and ∆covR mutant. For both experiments, three triplicates were done for each sample and each replicate was done in a different day to take into account the replica biases during statistical analysis.

first: Odile

last: Sismeiro

first: Hugo

last: Varet

first: Myriam

last: Gominet


title: Runx1-deficiency induced changes in transcription and chromatin accessibility in mK4 cells

status: Public on Jun 07 2021

city: Cincinnati

first: Matthew

last: Weirauch

state: Ohio

address: 3333 Burnet Avenue

department: Center for Autoimmune Genomics and Etiology (CAGE)

institute: Cincinnati Children's Hospital Medical Center

summary: We report the genome-wide effects of Runx1-deficiency in mK4 cells through RNA-seq, ATAC-seq, and ChIP-seq for Runx1 and Runx2.

overall_design: Triplicate samples of control mK4 and Runx1KO cells for RNA-seq, ATAC-seq, and Runx1 and Runx2 ChIP-seq in both cell types.

last: Hass

first: Raphael

last: Kopan

first: Leah

last: Kottyan


title: Expression data from early postnatal brain in autism model marmoset

status: Public on Apr 01 2021

city: Kodaira

first: Satoshi

last: Watanabe

state: Tokyo

address: 4-1-1 Ogawa Higashi

institute: National Center of Neurology and Psychiatry

summary:
Autism spectrum disorder (ASD) affects gene expression in early postnatal development. We used valproic acid (VPA)-induced ASD model marmosets.
Gene expression in VPA-exposed and unexposed (UE) marmosets were analyzed at 0, 3 and 6 months (M). We revealed three groups of differentially expressed genes based on the temporal patterns of modulation.

overall_design: Tissues from three cortical areas (Brodmann area 8, 12, and TE) of UE and VPA marmosets were isolated. RNA was extracted and hybridized on custom-made microarrays. We sought to obtain differentially expressed genes at each age.

first: Tomofumi

last: Oga

first: Tetsuya

last: Sasaki

first: Kayo

last: Sumida

first: Kohei

last: Hoshino

first: Koichi

last: Saito

first: Izuru

last: Miyawaki

first: Keiko

last: Nakagaki

first: Noritaka

last: Ichinohe


title: Fine-tuned repression of Drp1 driven mitochondrial fission primes a ‘stem/progenitor-like state’ to accelerate neoplastic transformation

status: Public on Apr 10 2021

city: Birmingham

first: Kasturi

last: Mitra

state: Alabama

address: University of Alabama, Birmingham

department: Genetics

institute: University of Alabama, Birmingham

summary: Mitochondria based priming of a stem/progenitor-like state involves fine-tuned repression of the master regulator of mitochondrial fission, Drp1, and drives carcinogen induced transformation in a keratinocyte model

overall_design: Comparison of scRNAseq data of parental HaCaT ketatinocyte line, their TCDD (1nM and 10nM) driven transformed counterparts, and after expression of control, weak and strong Drp1 shRNA.

first: Brian

last: Spurlock

first: Malay

last: Basu


title: Transcription start site analysis of Streptococcus agalactiae strain BM110

first: Rachel

last: Legendre

summary: Streptococcus agalactiae, also known as Group B streptococcus, emerged in the 1960s as a leading cause of septicemia and meningitis in neonates. It is also an increasing cause of infections in adults with underlying diseases. To characterize transcription start sites (TSS) in the hypervirulent ST17 lineage (strain BM110) we used a differential RNA-seq strategy, based on selective Tobacco Acid Pyrophosphatase (TAP) treatment and adapter ligation, which differentiates primary transcripts and processed RNAs

overall_design: We analyzed three dRNA seq experiments (TAP-treated versus TAP-untreated RNA) on the following RNA samples: 1) a pool of BM110 RNA prepared under mid-exponential (O.D600= 0.4) and early stationary phase (O.D600= 1.2) in a rich growth medium (TH) and under stationary phase (O.D600= 0.35) in a poor culture medium; 2) RNA prepared from a transconjugate of BM110 (after TnGBS1 transfer; TnGBS under non-integrated form) cultivated in a rich medium (TH) to late-exponential phase (O.D600= 0.8) in the presence of tetracycline 10mg/l; RNA from BM110 cultivated in a rich medium (TH) to late-exponential phase (O.D600= 0.8) in the presence of tetracycline 10mg/l.

first: I

last: Rosinski-Chupin

first: P

last: Glaser


title: NETSeq Analysis of the Effect of PARP-1 Knockdown in Drosophila Melanogaster

status: Public on Aug 06 2021

city: Louisville

first: Eric

middle: Christian

last: Rouchka

state: Kentucky

address: 522 East Gray Street

department: Biochemistry and Molecular Genetics

institute: University of Louisville

summary: Multiple roles for PARP1 have been elucidated including DNA damage repair, metabolic regulation, and cell cycle control. PARP1 also has an effect on chromatin structure, but this factor has not been well studied. Here, we strive to elucidate the effect of PARP1-mediated chromatin changes, specifically in the context of transcription and alternative splicing. Chromatin structure affects any process that occurs on the DNA, including transcription and splicing. Therefore, if PARP1 has an effect on chromatin structure, it will cause downstream changes in transcription and splicing. We investigated PARP1’s connection to splicing not only by evaluating splicing decisions, but also by studying its effect on splicing factors. We found that PARP1 has a multifaceted role in these processes. PARP1 presence influences splicing decisions by altering nucleosome deposition and histone post-translational modifications at exon-intron boundaries. Additionally, PARP1 occupancy modifies transcriptional elongation by hindering the rate of RNAPII movement. In this study, we show that through changes in chromatin structure, PARP1 is able to modify transcriptional elongation rates as well as alternative splicing decisions.

overall_design: Two conditions, wild type (WT) and PARP-1 knockdown (KD), were examined with two replicates per condition.  In both cases, a high band and low band were extracted for sequencing, resulting in eight total samples.

first: Matveeva

last: Elena

middle: C

first: Yvonne

middle: N

last: Fondufe-Mittendorf


title: CARS2HA

status: Public on Mar 15 2021

city: Ottawa

first: Anh-Thu

last: Dang

address: 40 Ruskin St

department: Biochemistry

institute: University of Ottawa Heart Institute

summary: Transfection experiments to investigate the role of CARS2 in macrophages.

overall_design: PMA differentiated THP-1 macrophages were transfected for 72 hours with CARS2 siRNA and NT2 control siRNA. RNA was harvested and the transcriptome was analyzed by transcription array. The experiment was repeated 3 times.

first: Anh

middle: T

first: Ruth

last: McPherson


title: Developmental and sexual dimorphic atlas of the prenatal mouse external genitalia at the single cell level

status: Public on May 20 2021

city: Research Triangle Park

first: Ciro

middle: Maurizio

last: Amato

state: NC

address: 111 Tw Alexander Dr

department: Reproductive and Developmental Biology Laboratory

institute: National Institute of Environmental Health Sciences

summary: Before the onset of sexual differentiation, male and female external genitalia are morphologically  indistinguishable. After the onset of sex-specific production of sex steroids by the gonads, the male and female external genitalia differentiate into either a penis or clitoris. Here we use single cell sequencing to investigate the similarities and differences of cell populations in the external genitalia during the critical sexual differentiation window in the mouse embryo. We found the male and female genitalia are largely  similar in cell composition and gene expression at the bipotential stage of development. As sexual differentiation ensues, sex steroid-dependent and -independent differences in cell populations arise, leading to dimorphic establishment of the external genitalia.

overall_design: Male and Female External Genitalia at stages E14.5, E16.5, and E18.5

first: Humphrey

last: Yao


title: Proatherogenic gene regulation explained by cell-type-specific miRNA profiling

status: Public on May 14 2021

city: Kuopio

first: Minna

last: Kaikkonen-Määttä

country: Finland

institute: A. I. Virtanen Institute

type: Non-coding RNA profiling by high throughput sequencing

summary: Regulation of coding and non-coding genes is studied from primary human aortic endothelial cells (HAECs), venous endothelial cells (HUVECs), aortic smooth muscle cells (HASMCs) and macrophages (CD14+) under pro-atherogenic stimuli (hypoxia, oxPAPC and hypoxia+oxPAPC) by integrating three different sequencing techniques: GRO-seq, miRNA-seq and RNA-seq.

overall_design: Three different sequencing techniques (GRO-Seq, RNA-Seq and miRNA-Seq) of four distinct cell types (HAEC, HUVEC, HASMC, CD14+/Macrophages) analysed under 3 stimuli (hypoxia, oxPAPC and hypoxia+oxPAPC).

first: M

last: Bouvy-Liivrand

last: Moreau

first: V

last: Tomas Bosch

first: K

last: Õunap

first: T

last: Örd


title: Transcriptome-wide search for Carpathian  goat factors associated with proviral load of small ruminant lentiviruses in goats

status: Public on Mar 04 2021

city: Kraków

first: Tomasz

last: Szmatola

address: Redzina 1c

department: OMEI

country: Poland

institute: University of Agriculture in Krakow

summary:
Purpose: RNA-sequencing (RNA-seq) was used to identify the changes in gene expression in goats carrying high (HPL) and low (LPL) proviral load of SRLV. For the first time, differentially expressed transcriptome profiles in these two group of animals were identified, and information about genes and mechanisms, and relevant pathways inferred via bioinformatics analyses. The results provided unique insights for further exploring and understanding the host responses to SRLV infection in goats.
Results: Data enabled to identify 1434 significant differentially expressed genes between HPL and LPL goats. Of these genes, 571 were upregulated and the remaining 863 genes were downregulated in HPL goats. GO enrichment analysis showed that the identified DEGs were found to have significantly enriched regulation of signaling receptor activity, the response to toxic substance, NADH dehydrogenase complex assembly, cytokine production, vesicle and vacuole organization. In turn, KEGG pathway tool classified DEGs that enrich molecular processes such as B and T cell receptor signaling pathways, natural killer cell-mediated cytotoxicity, Fc gamma R-mediated phagocytosis, toll-like receptor signaling pathways, TNF, mTOR signaling and Foxo signaling pathway, etc.
Conclusions: In this descriptive study, our findings revealed the changes in the host transcriptome expression profile between HPL and LPL goats during SRLV infection and suggested that changes in proviral load induced altering the host’s metabolic network and expression of genes related to host immune responses, including inflammation, cell locomotion, cytokine production, defense response etc. The above findings provided unique insights for further studies on the mechanisms underlying SRLV-host interactions.

overall_design: The whole blood transcriptome sequencing was performed for 12 samples collected form Carpathian goats using HiSeq High-Output v4 - SR (Illumina) into 50 single-end cycles.

first: Monika

last: Olech

first: Katarzyna

last: Ropka-Molik

last: Szmatoła

last: Piórkowska

first: Jacek

last: Kuźmak


title: A single cell atlas of human teeth (Pulp scRNA-seq)

status: Public on Feb 16 2021

city: Basel

first: Andreas

last: Moor

address: Mattenstrasse 26

department: Department of Biosystems Science and Engineering

country: Switzerland

institute: ETH

summary: Teeth exert fundamental functions related to mastication and speech. Despite their big biomedical interest, an overall picture of their cellular and molecular composition is still lacking. We here mapped the transcriptional landscape of the various stem cell populations and their microenvironments in human teeth at single-cell resolution. Our analysis identified significant cellular heterogeneity between the various dental tissues. Unexpectedly, we found that the molecular signatures of the stem cell populations were very similar in vivo, and that their distinctive behavior was due to substantial differences between their microenvironments. Furthermore, we showed that the evolutionarily conserved Notch signaling pathway is important for the interactions between dental stem cells and the diverse cell types composing their niches. Our findings reveal that the microenvironmental specificity is responsible for the major functional differences of the stem cells located in the various tooth compartments and open new perspectives towards dental cell-based therapeutic approaches.

overall_design:
Single-cell RNA sequencing analysis (10x) of human dental pulps and periodontium. For each tissue, the analysis was performed on biopsies obtained from 5 distinct patients. Healthy dental pulps and healthy periodontium were selected.

UPDATE: [12-09-2024] The processed data files for GSM4998458 and GSM4998459 were corrected.

first: Pierfrancesco

last: Pagella

first: Laura

last: de Vargas Roditi

first: Bernd

last: Stadlinger

middle: E

first: Thimios

last: Mitsiadis


title: A single cell atlas of human teeth

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

overall_design: Refer to individual Series


title: RNA-seq of liver after SHAM or CLP with and without dexamethasone treatment [24hrs]

status: Public on Feb 01 2021

city: Gent

first: Steven

last: Timmermans

address: Technologiepark 71

country: Belgium

institute: VIB-UGent

summary: Study of the occurrence of glucocorticoid resistance after CLP induced sepsis in mice

overall_design: Examination of changes in gene expression in livers of C57BL/6J mice after CLP or SHAM operation followed after 24 with an injection of PBS or DEX, with organ isolation 2h post-injection. A total 4 groups with 3 biological replicates/group were sequenced for a total of 12 samples

first: Jolien

last: Vandewalle

first: Ville

last: Paakinaho

first: Lies

last: Vancraeynest

first: Liza

last: Dewyse

first: Lise

last: Van Wyngene

first: Kelly

last: Van Looveren

first: Tineke

last: Vanderhaeghen

first: Charlotte

last: Wallaeys

first: Melanie

last: Eggermont

first: Sylviane

last: Dewaele

first: Leo

last: van Grunsven

first: Mieke

last: Dewerchin

first: Peter

last: Carmeliet

first: Karolien

last: De Bosscher

first: Johan

last: Van de Voorde

first: Jorma

middle: J

last: Palvimo

first: Claude

last: Libert


title: RNA-seq of liver after SHAM or CLP with and without dexamethasone treatment

first: Steven

last: Timmermans

overall_design: Examination of changes in gene expression in livers of C57BL/6J mice after CLP or SHAM operation followed after 6 with an injection of PBS or DEX, with organ isoloation 2h post-injection. A total 4 groups with 3 biological replicates/group were sequenced for a total of 12 samples

first: Jolien

last: Vandewalle

last: de Voorde


title: Global Translational Landscape of the Candida albicans Morphological Transition

status: Public on Dec 10 2020

city: San Antonio

first: David

last: Kadosh

state: Texas

address: 7703 Floyd Curl Dr., MC: 7758

department: Department of Microbiology, Immunology & Molecular Genetics

institute: University of Texas Health Science Center at San Antonio

summary: Candida albicans is a major human fungal pathogen that represents the fourth leading cause of hospital-acquired bloodstream infections in the U.S. and is associated with high mortality and/or morbidity rates in a wide variety of immunocompromised individuals, including cancer and AIDS patients. While the C. albicans morphological transition from yeast to filamentous cells is required for virulence, considerably little is known about translational mechanisms important for controlling this transition as well as other virulence-related processes in C. albicans and other human fungal pathogens. Using ribosome profiling, we report the first global translational profile associated with C. albicans morphogenesis. Strikingly, many genes involved in pathogenesis, filamentation, response to stress and cell wall organization show reduced translational efficiency (TE). Several of these genes are known to be strongly induced at the transcriptional level, suggesting that a translational fine-tuning mechanism is in place. Using a recently developed ORF-calling method, we have identified a significant number of potential uORFs in genes associated with pathogenesis and at least 57 potential novel ORFs, several of which appear to show altered TE in response to filamentation. Finally, using a novel method for global analysis of ribosome pausing from Ribo-seq data, we demonstrate an enrichment of ribosome pausing sites in C. albicans genes associated with protein synthesis and cell wall functions. Altogether, our results suggest that the C. albicans morphological transition is associated with widespread global translational alterations that do not simply reflect transcriptional changes and affect the expression of many genes associated with virulence-related processes and pathogenesis.

overall_design: Examination of gene expression by RNA-seq and Ribo-seq in 1 strain of Candida albicans grown under 2 conditions  (YEPD + serum at 37°C (filament-inducing) and YEPD at 30°C (non filament-inducing)). There are three biological replicates for each strain grown under each condition (12 samples total).

first: Saket

last: Choudhary


title: High intake of dietary sucrose induces sexually dimorphic metabolic adaptations in liver and adipose tissue

status: Public on Mar 01 2021

city: Downers Grove

first: Erin

last: Stephenson

state: IL

address: 555 31st street

institute: Midwestern University

summary: This data submission reports the effects of 12 weeks supplementaion of 10%w/v sucrose supplied in drinking water on the inguinal white adipose tissue mRNA profiles of male and female mice relative to control groups (littermates that received plain water instead). RNAseq was performed by Novogene and investigators performed all analyses downstream of readcount acquisition. Manuscript abstract: Almost all effective treatments for non-alcoholic fatty liver disease (NAFLD) involve reduction of adiposity, which suggests the metabolic axis between liver and adipose tissue is essential to NAFLD development. Since excessive dietary sugar intake may be an initiating factor for NAFLD, we have characterized the metabolic effects of liquid sucrose intake at concentrations relevant to typical human consumption in mice. We report that sucrose intake induces sexually dimorphic effects in liver, adipose tissue, and the microbiome; differences concordant with steatosis severity. We show that when steatosis is decoupled from impairments in insulin responsiveness, sex is a moderating factor that influences sucrose-driven lipid storage and the contribution of de novo fatty acid synthesis to the overall hepatic triglyceride pool. Our findings provide physiologic insight into how sex influences the regulation of adipose-liver crosstalk and highlight the importance of extrahepatic metabolism in the pathogenesis of diet-induced steatosis and NAFLD.

overall_design: Inguinal adipose tissue mRNA profiles of male and female C57BL6/J x C57BL6/N mice after receiving 10%w/v sucrose in their drinking water for 12 weeks beginning at 10 weeks of age (and littermate controls that received water for the same time duration)


title: Single cell transcriptome from aplastic anemia (AA) and healthy donors [Full-length RNA-seq]

status: Public on Mar 31 2021

city: Tianjin

first: Caiying

last: Zhu

address: Heping District, Nanjing Road, 288

institute: Institute of Hematology and Blood Disease Hospital

summary: Transcriptome analysis of hematopoietic stem and progenitor cells (HSPCs) from aplastic anemia (AA) and healthy donors

overall_design: Full length mRNA profiles of hematopoietic stem and progenitor cells (HSPCs) under aplastic anemia (AA) and healthy conditions were generated by deep sequencing at single cell resolution, using Illumina Hiseq

first: Chenchen

last: Wang

first: Yu

last: Lian

first: Peng

last: Wu

first: Tao

last: Cheng

first: Jun

last: Shi

first: Ping


title: The transition from quiescent to activated states in human hematopoietic stem cells is governed by dynamic 3D genome reorganization [Hi-C]

status: Public on Nov 23 2020

city: Toronto

first: Alexander

middle: James

last: Murison

state: Ontario

address: 101 College Street, TMDT room 11-706

institute: University Health Network

summary: We profiled chromatin accessibility in sorted hematopoietic populations. We used this to identify signatures of chromatin accessibility which discriminated LT-HSC from other hematopoietic stem and progenitor cell populations, discriminated by CTCF binding sites. We further validated this with RNA-Seq on sorted cord blood populations  following shCTCF, and Hi-C and CTCF ChIP-Seq on the OCIAML-2 cell line.

overall_design:
Hi-C was performed on the OCIAML-2 cell line
Note from submitter: Raw data has been submitted separately to the EGA since it contains patient-sensitive information

first: Alex

first: Kip

last: Arlidge

first: Naoya

last: Takayama


title: The transition from quiescent to activated states in human hematopoietic stem cells is governed by dynamic 3D genome reorganization

overall_design:
Refer to individual Series

Note from submitter: Raw data has been submitted separately to the EGA since it contains patient-sensitive information


title: The transition from quiescent to activated states in human hematopoietic stem cells is governed by dynamic 3D genome reorganization [RNA-Seq]

overall_design:
Gene expression profiling of RNA from 3 pools of purified hematopoietic stem cells and progenitors derived from human cord blood.
RNA-Seq in cultured LT-HSC populations transfected with shCtrl or shCTCF.

Note from submitter: Raw data has been submitted separately to the EGA since it contains patient-sensitive information.

first: Shinichiro

last: Takayanagi


title: The transition from quiescent to activated states in human hematopoietic stem cells is governed by dynamic 3D genome reorganization [ChIP-Seq]

overall_design:
CTCF ChIP-Seq in the cell line OCIAML-2
Note from submitter: Raw data has been submitted separately to the EGA since it contains patient-sensitive information

first: Helena

last: Boutzen

first: Stanley

last: Zhou


title: The transition from quiescent to activated states in human hematopoietic stem cells is governed by dynamic 3D genome reorganization [Low-C]

summary: Life-long blood production requires long-term hematopoietic stem cells (LT-HSC) - marked by stemness states involving quiescence and self-renewal - to transition into activated short-term HSC (ST-HSC) with reduced stemness. As few transcriptional changes underlie this transition, we used single-cell and bulk ATAC-seq on human HSC and stem/progenitor subsets (HSPC) to uncover chromatin accessibility signatures, one including LT-HSC (LT/HSPC signature) and another excluding LT-HSC (Act/HSPC signature). These signatures inversely correlated during early hematopoietic commitment and differentiation. The Act/HSPC signature contains CTCF binding sites mediating 351 chromatin interactions, engaged in ST-HSC but not LT-HSC, enclosing multiple stemness pathway genes active in LT-HSC and repressed in ST-HSC. CTCF silencing derepressed stemness genes, restraining quiescent LT-HSC from transitioning to activated ST-HSC. Hence, 3D chromatin interactions centrally mediated by CTCF, endow a gatekeeper function that governs the earliest fate transitions HSC make by coordinating disparate stemness pathways linked to quiescence and self-renewal.

overall_design:
2
Note from submitter: Raw data has been submitted separately to the EGA since it contains patient-sensitive information


title: The transition from quiescent to activated states in human hematopoietic stem cells is governed by dynamic 3D genome reorganization [ATAC-Seq]

overall_design:
ATAC-seq of Primary cord blood (CB) derived hematopoietic cells
Note from submitter: Raw data has been submitted separately to the EGA since it contains patient-sensitive information


title: Bulk RNA-seq of aplastic anemia (AA) and healthy donors

summary: Bulk RNA-seq data of  Lin-CD34+ hematopoietic stem and progenitor cells derived from bone marrow of healthy donors and untreated aplastic anemia  patients

overall_design: Mononuclear cells from 3 healthy donors and untreated aplastic anemia patients' bone marrow aspirates were isolated using Ficoll density gradient separation and cryopreserved in 90% FBS/ 10% DMSO for storage in liquid nitrogen. The thawing frozen cells were stained with human antibodies including lineage cocktail (CD3, CD14, CD16, CD19, CD20, CD56) (BV510, Biolegend) and CD34 (APC, Clone 581, BD Biosciences) antibodies. Lin-CD34+ HSPCs (cell count ranges from 130 to 2000) were sorted directly into cell lysis buffer on a BD FACSAria III. The reverse transcription and template switch steps were performed following the full-length Smart-seq2 protocol with some modifications. Concentration of oligd(T30VN) and template switch oligo (TSO) primers used for mRNA reverse transcription were double. The cDNA was fragmented using Covaris S220 instead of Tn5 transposase. The processes of end repair, polyA-tailing, adaptor ligation and library amplification were using KAPA Hyper Prep Kits (Kapa Biosystems, Cat# KK8504) and NEBNext Multiplex Oligos for Illumina (Index Primers Set 1) (NEB, Cat# E7335L).The 150bp paired-end reads were generated from Illumina NovaSeq6000 platform. For data processing, TSO primer, polyA tail, adaptor, and low-quality sequence (N > 10%) were trimmed using Trimmomatic (version 0.36). Clean reads were aligned against the human GRCh38 genome using STAR (version 2.7)). Duplicate reads were identified and removed by using Picard(version 2.17.6). MATS(version 4.0.2) and DaPars(version 0.9.0) to perform alternative splicing and alternative polyadenylation analysis, respectively. Gene quantification was using HTSeq (version 0.9.1).


title: Genome-wide investigation of the dynamic changes of epigenome modifications after DNA methylation editing [MBD-seq]

status: Public on Nov 10 2020

city: Stuttgart

first: Albert

last: Jeltsch

address: Allmandring 31

department: Institute of Biochemistry and Technical Biochemistry

country: Germany

institute: University Stuttgart

type: Methylation profiling by high throughput sequencing

summary: The aim of this study was to investigate the stability of DNA methylation, the dynamics of different histone modifications and the changes in expression after genome-wide introduction of DNA methylation in promotor CpG islands. Therefore, the catalytic domain of DNMT3A was fused to a zinc finger protein and expressed for three days to globally introduce de novo DNA methylation and subsequently,  the changes in the epigenome were monitored for up to eleven days.

overall_design: A stable HEK293 cell line was constructed with the catalytic domain of DNMT3A fused to a zinc finger (ZnF-3AC) which is under the control of a doxycyclin (dox)-inducible promoter. GFP is co-expressed via an IRES and serves as a reporter. Cells were either harvested before dox treatment ("no dox") or grown under dox conditions for three days ("3d dox"). GFP-positive cells were enriched by FACS after 3d dox and a fraction of these cells was re-seeded on a 6-Well-plate without supplementation of dox. Five and eight days after dox removal ("5d / 8d / 11d off"), cells were harvested and a fraction of cells was re-seeded again. After eleven days of dox removal ("11d off"), cells were harvested and the experiment was stopped.

first: Julian

last: Broche

first: Goran

last: Kungulovski

first: Pavel

last: Bashtrykov

first: Philipp

last: Rathert


title: Transcriptome profiling of zebrafish optic fissure fusion

status: Public on Oct 22 2020

city: London

first: Mariya

last: Moosajee

address: 11-43 Bath Street

department: Institute of Ophthalmology

country: United Kingdom

institute: UCL

summary: Incomplete fusion of the optic fissure leads to ocular coloboma, a congenital eye defect that affects up to 7.5 per 10,000 births and accounts for up to 10 percent of childhood blindness. The molecular and cellular mechanisms that facilitate optic fissure fusion remain elusive. We have profiled global gene expression during optic fissure morphogenesis by transcriptome analysis of tissue dissected from the margins of the zebrafish optic fissure and the opposing dorsal retina before (32 hours post fertilisation, hpf), during (48 hpf) and after (56 hpf) optic fissure fusion. Differential expression analysis between optic fissure and dorsal retinal tissue resulted in the detection of several known and novel developmental genes. The expression of selected genes was validated by qRT-PCR analysis and localisation investigated using in situ hybridisation. We discuss significantly overrepresented functional ontology categories in the context of optic fissure morphogenesis and highlight interesting transcripts from hierarchical clustering for subsequent analysis. We have identified netrin1a (ntn1a) as highly differentially expressed across optic fissure fusion, with a resultant ocular coloboma phenotype following morpholino antisense translation-blocking knockdown and downstream disruption of atoh7 expression. To support the identification of candidate genes in human studies, we have generated an online open-access resource for fast and simple quantitative querying of the gene expression data. Our study represents the first comprehensive analysis of the zebrafish optic fissure transcriptome and provides a valuable resource to facilitate our understanding of the complex aetiology of ocular coloboma.

overall_design: We used RNA-seq to identify differentially expressed genes across optic fissure fusion in zebrafish. Samples were isolated retinal regions including the optic fissure (OF) region and control dorsal retina (DR) at timepoints; prefusion (32 hpf), fusing (48 hpf) and post fusion (56 hpf). 5 biological replicates.

first: Nicholas

last: Owen

first: Rose

last: Richardson

first: Maria

last: Toms

last: Moosjaee


title: Prognostic significance of interferon-γ and its signaling pathway in early breast cancer depends on the molecular subtypes

status: Public on Sep 22 2020

city: Mainz

first: Marcus

last: Schmidt

address: Langenbeckstr. 1

department: Universitäres Centrum für Tumorerkrankungen

institute: Universitätsmedizin Mainz

summary: Interferons are crucial for adaptive immunity and play an important role in the immune landscape of breast cancer. Using microarray-based gene expression analysis, we examined the subtype specific prognostic significance of interferon-γ (IFN-γ) as a single gene as well as an IFN-γ signature covering the signaling pathway in 461 breast cancer patients. Prognostic significance of IFN-γ as well as the IFN-γ signature for metastasis-free survival (MFS) were examined using Kaplan Meier as well as univariate and multivariate Cox regression analyses in the whole cohort and in different molecular subtypes. Kaplan Meier curves and univariate Cox regression analyses showed that the prognostic significance of IFN-γ as a single gene was limited to basal-like breast cancer (P=0.033). In contrast, the IFN-γ associated gene signature was a significant prognostic factor in the whole cohort (HR 1.554; 95%CI 1.1099-2.199; P=0.013) as well as in the luminal B (P=0.007) and HER2-positive (P=0.033) molecular subtype with borderline significance in basal-like breast cancer(P=0.050). In multivariate analysis, the IFN-γ signature retained its independent prognostic significance (HR 2.287; 95% CI: 1.410-3.633;P<0.001) in the entire cohort. These results underline the subtype-dependent prognostic influence of the immune system in early breast cancer.

overall_design:
461 patients with early breast cancer, who received surgery between 1986 to 2000 at the Department of Gynecology and Obstetrics of the University Medical Center Mainz, entered the study. We included all consecutive patients with an adequate amount of fresh-frozen tumor tissue available for successful Affymetrix microarray analysis.

***CEL files not available for 109 patients

first: M

last: Gehrmann


title: Genome-wide investigation of the dynamic changes of epigenome modifications after DNA methylation editing [RNA-seq]

summary: The aim of this study was to investigate the stability of DNA methylation, the dynamics of different histone modifications and the changes in expression after genome-wide introduction of DNA methylation in promotor CpG islands. Therefore, the catalytic domain of DNMT3A was fused to a zinc finger protein and expressed for three days to globally introduce de novo DNA methylation and subsequently, the changes in the epigenome were monitored for up to eleven days.

overall_design: A stable HEK293 cell line was constructed with the catalytic domain of DNMT3A fused to a zinc finger (ZnF-3AC) which is under the control of a doxycycline (dox)-inducible promoter. GFP is co-expressed via an IRES and serves as a reporter. Cells were either harvested before dox treatment ("no dox") or grown under dox conditions for three days ("3d dox"). GFP-positive cells were enriched by FACS after 3d dox and a fraction of these cells was re-seeded on a 6-well-plate without supplementation of dox. Five and eight days after dox removal ("5d / 8d / 11d off"), cells were harvested and a fraction of cells was re-seeded again. After eleven days of dox removal ("11d off"), cells were harvested and the experiment was stopped.


title: Unveiling Functional Heterogeneity in Breast Cancer MCTS through Single-Cell RNA seq

status: Public on Jul 29 2020

city: Mexico city

first: Aarón

last: Vázquez-Jiménez

state: Mexico city

address: Periferico Sur 4809

country: Mexico

institute: INMEGEN

summary: The goal of this study was to describe functional heterogeneity in cancer using MCTS MCF7 as tumor model, two time points were considered as an early and advanced tumor stages. Despite time, MCTS MCF7 work as a systemic unit using task stratification with the ultimate goal to promote tumor survival.

overall_design: MCF7 mRNA profiles of 6-day old MCTS and 19-day old MCTS were generated by deep sequencing.

first: Erick

last: Muciño-Olmos

first: Ugo

last: Avila-Ponce

first: Meztli

last: Matadamas-Guzman

first: Vilma

last: Maldonado

first: Taide

last: Lopez

first: Abraham

last: Hernández-Hernández

first: Osbaldo

last: Resendis-Antonio


title: Keystone genes for tooth development

status: Public on Nov 01 2020

city: Helsinki

first: Jukka

last: Jernvall

address: P.O. Box 56 (Viikinkaari 9)

institute: University of Helsinki

sample_organism:
Mus musculus
Rattus norvegicus
Myodes glareolus

overall_design: Refer to individual Series


title: RNA sequencing of pre-treatment primary cervical cancer

status: Public on Jun 03 2020

city: St. Louis

first: Jin

last: Zhang

address: 4511 Forest Park Parkway

department: Radiation Oncology

summary: Investigate the transcriptomic differences between HPV-positive and HPV-negative primary cervical tumors.

overall_design: Whole transcriptome sequencing was performed on 68 pre-treatment, primary cervical cancer samples from cervical cancer patients treated at the Washington University School of Medicine. A minimum of 0.5µg of RNA with RIN > 7 was extracted for library preparation. Sequencing was performed using Illumina HiSeq 3000, 1x50nt, ~40 million reads per sample), and aligned to GRCh38 using STAR 2.7.0f.

first: Fiona

last: Ruiz

first: Julie

last: Schwarz

first: Matthew

last: Inkman

first: Kay

last: Jayachandran

first: Perry

middle: W

last: Grigsby

first: Christopher

middle: A

last: Miller

first: Michael

last: McLellan


title: RNA-seq analysis of immune responses from mouse bone marrow derived dendritic cells stimulated with 7 pattern recognition receptor (PRR) ligands along with their pairwise and triplet combinations

status: Public on Jul 01 2020

city: Chicago

first: Nicolas

last: Chevrier

state: Illinois

address: 5640 South Ellis Avenue

department: Pritzker School of Molecular Engineering

institute: The University of Chicago

summary: The immune system makes decisions in response to combinations of multiple microbial inputs. We do not understand the combinatorial logic governing how higher-order combinations of microbial signals shape immune responses. Here, using coculture experiments and statistical analyses, we discover a general property for the combinatorial sensing of microbial signals, whereby the effects of triplet combinations of microbial signals on immune responses can be predicted by combining the effects of single and pairs. Mechanistically, we find that singles and pairs dictate the information signaled by triplets in mouse and human DCs at the levels of transcription, chromatin and protein secretion. We exploit this simplifying property to develop cell-based immunotherapies prepared with adjuvant combinations that trigger protective responses in mouse models of cancer. We conclude that the processing of multiple input signals by innate immune cells is governed by pairwise effects, which will inform the rationale combination of adjuvants to manipulate immunity.

overall_design: mRNA expression profiles of mouse bone marrow derived dendritic cells stimulated for 6 hours with seven PRR ligands in singles, their pair and triplet combinations generated by RNA-seq in triplicates using illumina nextseq 550

first: Surya

last: Pandey


title: Expression data of mRNA/LncRNA from megakaryocytes in MLL-AF9 AML mouse versus healthy control bone marrow

status: Public on Jun 25 2020

first: Caiying

last: Zhu

summary:
Thrombocytopenia is a major and fatal complication for AML, while what happened to megakaryopoiesis and thrombopoiesis in AML remains unknown.
Megakaryocytes have been recognized as essential HSC niche cells for their function to maintain HSC quiescence and support HSC regeneration. Megakaryocytes are robustly affected in AML bone marrow, while the alterations of their platelet-releasing and HSC supportive function are incompletely understood.

overall_design: Megakaryocytes (SSChigh CD41high, DNA content ≧ 8N) were isolated from MLL-AF9 induced AML mice and healthy control mice bone marrow by flow cytometry.

first: Yuemin

last: Gong

first: Ai

last: Gao


title: Single cell RNA-seq of long-term  hematopoietic stem cells (LT-HSCs) and common myeloid progenitors (CMPs)

summary: We aimed to reseach the differences between IL4Rα high and low expression LT-HSC/CMP,our data revealed distinct sensitivities of HSCs and common myeloid progenitors (CMPs) to IL4-induced apoptosis, and IL4Rahigh HSCs were more susceptible to unfolded protein response (UPR) and irradiation-induced apoptosis.

overall_design: LT-HSCs and CMPs were purified by FACS sorting based on cell surface markers:Lin-cKit+Sca1+Flt3-CD34-  for LT-HSCs and Lin-cKit+Sca1-CD16/32-CD34+ for CMPs.

first: Tao

last: Cheng

first: Fuchou

last: Tang


title: Correction of ALS-related phenotypes in iPSC-derived motor neurons carrying a hexanucleotide expansion mutation in C9orf72 by CRISPR/Cas9 genome editing and homology-directed repair

status: Public on May 19 2020

city: Oxford

first: Kevin

last: Talbot

address: John Radcliffe Hospital, Headley Way

department: Nuffield Department of Clinical Neurosciences

institute: University of Oxford

summary: The G4C2 hexanucleotide repeat expansion (HRE) in C9orf72 is the commonest cause of familial amyotrophic lateral sclerosis (ALS). A number of different methods have been used in an attempt to generate isogenic control lines using CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 and NHEJ by deleting the repeat region without replacing it with the normal repeat size, but typically this strategy carries the risk of creating indels and genomic instability. In this study we demonstrate complete correction of an induced pluripotent stem cell (iPSC) line derived from a C9orf72-HR positive ALS patient using CRISPR/Cas9 genome editing and homology directed repair (HDR), resulting in replacement of the excised region with a donor template carrying the wild-type repeat size to maintain the genetic architecture of the locus. The isogenic correction of the C9orf72 HRE restored normal expression and methylation at the C9orf72 locus, reduced intron retention in the edited lines, and abolished pathological phenotypes associated with the C9orf72 HRE expansion in iPSC derived motor neurons (iPSMNs). RNA sequencing of the mutant line identified 2220 differentially expressed genes compared to its isogenic control. Enrichment analysis demonstrated an over-representation of ALS relevant pathways in the presence of the C9orf72 HRE, including calcium ion dependent exocytosis, synaptic transport and the KEGG ALS pathway, as well as new targets of potential relevance to ALS pathophysiology.Complete correction of the C9orf72 HRE in iPS MNs by CRISPR/Cas9 mediated HDR provides an ideal model to study the earliest effects of the hexanucleotide expansion on cellular homeostasis and the key pathways implicated in ALS pathophysiology.

overall_design: We sequenced a total of seven edited samples (4 Ed-02-01 and 3 Ed-02-02), four samples with the hexanucleotide expansion (all C9-02-02) and one control patient sample.


title: PDGFB-expressing MSCs improve human hematopoietic stem cell engraftment in immunodeficient mice

status: Public on Jun 22 2020

summary: The bone marrow (BM) niche regulates multiple HSC processes. Clinical treatment for hematological malignancies, by HSC transplantation often requires preconditioning total body irradiation, which severely and irreversibly impairs the BM niche and HSC regeneration. Novel strategies to enhance HSC regeneration in irradiated BM are needed. We compared the effects of niche factors EGF, FGF2 and PDGFB on HSC hematopoietic regeneration using human MSCs that were transduced with these factors via lentiviral vectors. Among above niche factors tested, PDGFB-MSCs most significantly improved human hematopoietic cell engraftment in immunodeficient mice. PDGFB-MSC-treated BM more efficiently enhanced transplanted human HSC self-renewal in secondary transplantations from primary recipients. Although PDGFB-MSCs did not directly increase HSC expansion in vitro, GSEA revealed anti-apoptotic signaling being increased in PDGFB-MSCs versus GFP-MSCs. PDGFB-MSCs had enhanced survival and expansion after transplantation, leading to an enlarged humanized niche cell pool. Our study demonstrates the efficacy of MSC-mediated niche factors in clinical HSC transplantation for patients.

overall_design: MSCs were transduced with Lenti EF1-GFP and Lenti EF1-PDGFB to obtaine GFP-MSCs and PDGF-MSCs, and the in vivo experiments proved that PDGFB-MSCs increase human HSC engraftment in immunodeficient mice.

first: Linping

last: Hu

first: Xiuxiu

last: Yin

first: Xiao-Bing


title: Targeting RABL6A-RB1 signaling suppresses malignant peripheral nerve sheath tumors

status: Public on Feb 11 2020

city: Iowa City

first: Benjamin

last: Darbro

state: IA

address: 200 Hawkins Drive

institute: University of Iowa

summary: Malignant peripheral nerve sheath tumors (MPNSTs) are deadly sarcomas that lack effective therapies. In most MPNSTs, the retinoblastoma (RB1) tumor suppressor is disabled by hyperactivation of cyclin dependent kinases (CDKs), commonly through loss of CDK inhibitory proteins such as p27(Kip1). RABL6A is an inhibitor of RB1 whose role in MPNSTs is unknown. To gain insight into MPNST development and establish new treatment options, we investigated RABL6A-RB1 signaling and CDK inhibitor-based therapy in MPNSTs.

overall_design: We examined patient-matched MPNSTs and precursor lesions by RNA-Seq and IHC. Molecular and biological effects of silencing RABL6A and/or p27 in MPNST lines and normal human Schwann cells were determined. Tumor suppressive effects of CDK inhibitors were measured in MPNST cells and orthotopic tumors.

first: Jordan

last: Kohlmeyer

first: Courtney

last: Kaemmer

first: Casey

last: Pulliam

first: Chandra

last: Maharjan

first: Allison

middle: M

last: Samayoa

first: Heather

last: Major

first: Kendall

last: Cornick

first: Vickie

last: Knepper-Adrian

first: Rajesh

last: Khanna

first: Jessica

last: Sieren

first: Mariah

last: Leidinger

first: David

last: Meyerholz

first: Kokou

middle: D

last: Zamba

first: Jill

last: Weimer

first: Rebecca

last: Dodd

first: Munir

middle: R

last: Tanas

first: Dawn

last: Quelle


title: Genome-wide investigation of the dynamic changes of epigenome modifications after DNA methylation editing

first: Albert

last: Jeltsch

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


title: Loss of thymidine kinase 1 inhibits lung cancer growth and metastatic attributes by reducing GDF15 expression

status: Public on Sep 23 2019

city: Birmingham

first: Narendra

last: Wajapeyee

state: AL

address: 720 20th Street South, Kaul 540A

department: Department of Biochemistry and Molecular Genetics

institute: University of Alabama at Birmingham

summary: Metabolic alterations that are critical for cancer cell growth and metastasis are one of the key hallmarks of cancer. Here, we show that thymidine kinase 1 (TK1) is significantly overexpressed in tumor samples from lung adenocarcinoma (LUAD) patients relative to normal controls, and this TK1 overexpression is associated with significantly reduced overall survival and cancer recurrence. Genetic knockdown of TK1 with short hairpin RNAs (shRNAs) inhibits both the growth and metastatic attributes of LUAD cells in culture and in mice. We further show that transcriptional overexpression of TK1 in LUAD cells is driven, in part, by MAP kinase pathway in a transcription factor MAZ dependent manner. Using targeted and gene expression profiling-based approaches, we then show that loss of TK1 in LUAD cells results in reduced Rho GTPase activity and reduced expression of growth and differentiation factor 15 (GDF15). Furthermore, ectopic expression of GDF15 can partially rescue TK1 knockdown-induced LUAD growth and metastasis inhibition, confirming its important role as a downstream mediator of TK1 function in LUAD. Collectively, our findings demonstrate that TK1 facilitates LUAD tumor and metastatic growth and represents a target for LUAD therapy.

overall_design: A549 cells stably expressing two individual shRNAs against TK1 or as a control A549 cells expressing non-specific shRNAs were used to prepare the total RNA, which was then used to analyze for gene expression using Illumina HumanHT-12 V4.0 expression beadchip

first: Parmanand

last: Malvi


title: Gene expression profiles in rat alveolar macrophages exposure to multi-walled carbon nanotubes

status: Public on Sep 07 2019

city: Tsukuba

first: Katsuhide

last: Fujita

address: 16-1 Onogawa

department: Research Institute of Science for Safety and Sustainability

institute: National Institute of Advanced Industrial Science and Technology

summary: To evaluate the biological effects at the transcriptional level of manufactured nanomaterials, we performed whole genome microarrays of rat alveolar macrophages (NR8383) exposed to multi-walled carbon nanotubes (MWCNTs) with different physicochemical properties.

overall_design: Rat alveolar macrophages (NR8383) were exposed to 100 µg/mL of rigid needle-like shaped MWCNTs (MW1 and MW2), or bent-shaped MWCNTs (MW3 and MW4), and 50 µg/mL of straight and thin-shaped MWCNTs (MW5 and MW6) for 24 hours, respectively. The experiments were performed using control for each experiment (n=4). Gene expression profiles in rat alveolar macrophages exposure to submicron carbon fibers Cyanine-3-labeled cRNA prepared from cells was hybridized to a Whole Rat Genome Microarray. The scanned images of hybridized microarray slides were analyzed numerically to evaluate the biological effects at the transcriptional level of MWCNTs with different physicochemical properties on NR8383.

first: Sawae

last: Obara


title: Differentiation of transplanted haematopoietic stem cells tracked by single-cell transcriptomic analysis

status: Public on May 05 2020

first: Caiying

last: Zhu

summary: Transcriptome analysis of hematopoietic cells under homeostasis and regeneration at single cell resolusion

overall_design: 3' enriched mRNA profiles of hematopoietic cells under homeostsis and regeneration were generated by deep sequencing at single cell resolution, using Illumina Hiseq 4000

first: Sha

last: Hao

first: Fang

last: Dong

first: Hui

last: Cheng

first: Xiaofang

last: Wang

first: Peng

last: Wu

first: Ai

last: Gao

first: Ji

first: Yun

first: FuChou

last: Tang

first: Ping

first: Tao


title: RNA-seq analysis of transcriptomes of IL35-Treg cells and the Blimp1-Treg cells

status: Public on Aug 31 2019

city: Beijing

first: Xundong

last: Wei

address: 1st West Beichen, Chaoyang

department: CAS Key Laboratory of Pathogenic Microbiology and Immunology

institute: Institute of Microbiology, Chinese Academy of Sciences (CAS)

summary: To gain in depth transcriptional information about the two subsets of effector Tregs, we performed RNA-seq analysis to compare the transcriptomes of Thy1.1+Blimp1- (Ebi3-Tregs) and Thy1.1-Blimp1+ (Blimp1-Tregs) Tregs. We found ~173 unique genes with differential expression between the two effector subsets.

overall_design: Transcriptioanl profiles of Ebi3-Treg (CD4+CD25+Thy1.1+Blimp1-) and Blimp1-Treg (CD4+CD25+Thy1.1-Blimp1+) isolated from 35EbiT × Blimp1-GFP KI reporter mice were generated by RNA-sequencing.

first: Xuyu

last: Zhou


title: Expression of RAW264.7 cells stimulated with RANKL and treated with supernatant from Lactobacillus reuteri

status: Public on Aug 13 2019

city: Houston

first: Robert

last: Britton

state: TX

address: 1 Baylor Plaza

institute: Baylor College of Medicine

summary: Analysis of gene expression in RAW264.7 cells stimulated for osteoclastogenesis and then treated with cell culture supernatant from Lactobacillus reuteri. Results will offer insight into targeted mechanisms suppressing osteoclastogenesis

overall_design:
Total RNA obtained from RAW264.7 Cells at timepoints day 1, 3, and 5 under conditions of vehicle (MEM-alpha) as compared to treatment (L. reuteri).

***Raw data was not able to upload to SRA***

first: Darin

last: Quach


title: Inflammation-produced TNFα protects hematopoietic stem cells from necroptosis and promotes hematopoietic regeneration

status: Public on Jul 01 2019

city: Memphis

first: Masayuki

last: Yamashita

state: TN

address: 262 Danny Thomas Place

department: Division of Experimental Hematology, Department of Hematology

institute: St. Jude Children's Research Hospital

summary: To gain molecular insights into the differential effect of TNFα between hematopoietic stem cells (HSC) and downstream myeloid progenitors, we performed RNA-sequencing analyses of HSCs and granulocyte-macrophage progenitors (GMP) treated with TNFα both ex vivo and in vivo.

overall_design: RNA sequencing of 3 biological replicates of HSCs (Lin-/cKit+/Sca1+/Flk2-/CD48-/CD150+) and GMPs (Lin-/cKit+/Sca1-/FcγR+/CD34+) treated ± TNFα both ex vivo for 3 and 12 hours and in vivo for 3 hour (1x3hr). For ex vivo treatment of TNFα, HSCs and GMPs were isolated by FACS from C57BL/6 mouse bone marrow (BM) and cultured in liquid media ± TNFα for either 3 or 12 hours. For in vivo treatment, HSCs and GMPs were isolated from C57BL/6 mice 3 hours after a single injection of PBS or TNFα.

first: Emmanuelle

last: Passegué


title: Reprograming of gene expression and DNA methylation during initiation stages of the different root types in rice

status: Public on Feb 01 2020

city: Wuhan

first: shaoli

last: zhou

state: Hubei

address: shizishan street

department: National Key Laboratory of Crop Genetic Improvement

institute: Huazhong Agricultural University

summary: Rice possesses a fibrous root system with a primary root, lateral roots and crown roots. The cellular origins and early morphologies of the three root types vary greatly, but the adult structures are remarkably similar. Previous studies have highlighted diverse mechanisms involved in rice roots formation However, the gene expression reprograming and the underling epigenetic mechanisms of cell differentiation and initiation of the different roots are not studied. Here, we analyzed spatiotemporally resolved transcriptomes and DNA methylomes during the initiation processes of the three root types using a precise laser microdissection (LM) coupled with RNA-Seq and BS-seq. The analysis reveals distinct gene expression programs during the first stages during the initiation of the three root types. DNA methylome analysis uncovers a dynamic but distinct CHH methylation reprogramming during initiation of the three roots, with a genome-wide decrease of CHH methylation in crown and lateral root initials, but an increase in embryonic root primordium. In addition, a more drastic reprogramming of CHH methylation was observed in lateral root initials. Together, the results provide stage-specific gene expression signatures of the rice roots initiation and show distinct epigenetic and gene expression reprograming during the formation of the three different root types in rice.

overall_design: RNA-seq and BS-seq data of four stages of rice crown, lateral, embryonic root initials derived from laser microdissection, two biological replicates were represented for each sample.

first: Shaoli

first: Wei

last: Jiang

first: Yu

last: Zhao


title: RNA sequencing of GLO1-depleted MDA-MB-231 breast cancer cells

status: Public on Nov 07 2018

city: Liège

first: Marie-Julie

last: Nokin

address: Avenue Hippocrate

department: GIGA-Cancer

institute: University of Liège

summary: We reported the expression of a pro-metastatic signature in GLO1-depleted MDA-MB-231 cells compared to control.

overall_design: RNA sequencing was performed on 3 biological replicates of 2 clones of GLO1-silenced (shGLO1) cells and 1 control (shNT) clone

first: Akeila

last: Bellahcène

first: Vincent

last: Castronovo

first: Benoit

last: Charloteaux


title: Mutant FUS and ELAVL4 (HuD) aberrant crosstalk in Amyotrophic Lateral Sclerosis

status: Public on Jun 13 2019

city: Berlin

first: Emanuel

last: Wyler

address: Robert Roessle Str 10

department: Berlin Institute for Medical Systems Biology

institute: Max Delbrück Center for Molecular Medicine

summary: Determination of RNAs bound by wildtype and P525L mutant FUS in human iPSC-derived motoneurons using PAR-CLIP (Photoactivatable Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation)

overall_design: First, endogeneous FUS was immunoprecipitated from wildtype and FUS-P525L mutant motoneurons. Second, FUS wildtype or the P525L mutant was ectopically expressed as a flag-fusion protein and immunoprecipitated using an anti-flag antibody.

first: Riccardo

last: De Santis

first: Vincenzo

last: Alfano

first: Valeria

last: de Turris

first: Alessio

last: Colantoni

first: Laura

last: Santini

first: Maria

middle: G

last: Garone

first: Giuseppe

last: Antonacci

first: Giovanna

last: Peruzzi

first: Emma

last: Sudria-Lopez

first: Markus

last: Landthaler

first: R

last: Pasterkamp

first: Irene

last: Bozzoni

first: Alessandro

last: Rosa


title: Loss of Asxl1 Alters Mesenchymal Stem Cell Fate through H3K4me3 [ChIP-seq]

status: Public on Dec 08 2018

city: Tianjin

first: Caiying

last: Zhu

address: Heping District, Nanjing Road, 288

institute: Institute of Hematology and Blood Disease Hospital

summary: De novo ASXL1 mutations are found in patients with Bohring-Opitz syndrome (BOS), a disease with severe developmental defects and early childhood fatality. The underlying pathologic mechanisms remain largely unknown. Using Asxl1-targeted murine models, we found that Asxl1 global loss or conditional deletion in osteoblasts and their progenitors in mice leads to significant bone loss and markedly decreased numbers of marrow mesenchymal stem/progenitor cells (MSPCs) compared with wild-type (WT) littermates. Asxl1 null MSPCs display impaired self-renewal and skewed differentiation from osteoblasts towards adipocytes. ChIP-seq data identified that ASXL1 and H3K4me3 co-occupy the promoter regions of genes critical for MSPC self-renewal. Loss of Asxl1 diminished the genome enrichment of H3K4me3. Combined analysis of RNA-seq and ChIP-seq data revealed that Asxl1 loss in MSPCs altered the expression of ASXL1/H3K4me3 target genes controlling self-renewal/lineage commitment. Our study unveil a pivotal role of ASXL1 in H3K4me3-associated bone homeostasis

overall_design: Identification of ASXL1 binding profile in WT MSPCs and examination of 3 different histone modifications in WT and Asxl1-/- MSPCs.

first: Peng

last: Zhang

first: Caihong

last: Xing

first: Qian-Fei

last: Wang

first: Feng-Chun

last: Yang


title: Comparison of hepatic NRF2 and AHR binding in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treated mice demonstrates NRF2-independent PKM2 induction

status: Public on Jun 07 2018

city: East Lansing

first: Rance

last: Nault

state: United States

address: 1355 Bogue St. B403

department: Department of Pharmacology and Toxicology

institute: Michigan State University

overall_design: Refer to individual Series


title: Transcription factors operate across disease loci: EBNA2 in autoimmunity

status: Public on Jan 17 2018

city: Cincinnati

first: Matthew

last: Weirauch

address: 3333 Burnet Avenue

department: Center for Autoimmune Genomics and Etiology (CAGE)

institute: Cincinnati Children's Hospital Medical Center

summary: Explaining the genetics of many diseases is challenging because most associations localize to regulatory regions. We present a novel computational method for discovering disease-driving mechanisms acting across multiple disease-associated, non-coding genomic regions. Application to a matrix of 213 phenotypes and 1,544 transcription factor (TF) binding datasets identifies 2,264 significant associations for hundreds of TFs in 92 phenotypes, including prostate and breast cancers. Strikingly, nearly half of the systemic lupus erythematosus risk loci are occupied by the Epstein-Barr virus EBNA2 protein and 24 human TFs, revealing an important gene-environment interaction. EBNA2-anchored associations also exist in multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, type 1 diabetes, juvenile idiopathic arthritis, and celiac disease. Instances of allele-dependent DNA binding and downstream effects on gene expression at plausibly causal autoimmune variants support a genetic mechanism of pathogenesis centered on EBNA2. Our results nominate mechanisms operating across disease risk loci, suggesting new paradigms of disease origins.

overall_design: To identify differentially expressed genes associated with EBV infection.

first: John

middle: B

last: Harley

first: Xiaoting

last: Chen

first: Mario

last: Pujato

first: Daniel

last: Miller

first: Avery

last: Maddox

first: Carmy

last: Forney

first: Albert

middle: F

last: Magnusen

first: Arthur

last: Lynch

first: Kashish

last: Chetal

first: Masashi

last: Yukawa

first: Artem

last: Barski

first: Nathan

last: Salomonis

first: Kenneth

last: Kaufman

first: Leah

last: Kottyan


title: Hepatic pyruvate kinase muscle isoform 2 (Pkm2) induction in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-elicited oxidative stress is independent of NRF2  (RNA-Seq)

summary: Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces hepatic oxidative stress following activation of the aryl hydrocarbon receptor (AhR). Our recent studies revealed induction of pyruvate kinase muscle isoform 2 (Pkm2) as a novel antioxidant response in normal differentiated hepatocytes. To investigate cooperative regulation between nuclear factor, erythroid derived 2, like 2 (Nrf2) and the AhR, hepatic ChIP-seq analyses were integrated with RNA-seq time course data from mice treated with TCDD for 2 - 168h. ChIP-seq analysis 2h following TCDD treatment revealed genome-wide changes in NRF2 binding. 842 NRF2 enriched regions were in the regulatory region of differentially expressed genes (DEGs) while 579 DEGs showed both NRF2 and AhR enrichment. Sequence analysis showed over-representation of AhR and NRF2 binding motifs in these regions, though presence of motifs were largely independent. NRF2 was negligibly enriched within the Pkm gene loci in a closed chromatin region despite its role in antioxidant defenses. Furthermore, TCDD induced Pkm2 in primary hepatocytes from wild-type and Nrf2 null mice, indicating NRF2 is not required. Although NRF2 and AhR cooperate in the regulation of gene expression associated with antioxidant responses, the induction of Pkm2 by TCDD is not dependent on ROS-mediated activation of NRF2.

overall_design: Three biological replicates at each time point (2, 4, 8, 12, 24, 72, 168h) for mice gavaged with 30 μg/kg TCDD and time-matched sesame oil vehicle control.

first: Claire

last: Doskey

first: Kelly

last: Fader

first: Timothy

last: Zacharewski


title: Pioneer factor-nucleosome binding events during differentiation are motif-encoded

status: Public on Jun 25 2019

city: Chapel Hill

first: Michael

last: Meers

address: 250 Bell Tower Dr.

institute: UNC Chapel Hill

summary: Though the in vitro structural and in vivo spatial characteristics of transcription factor (TF) binding are well defined, TF interactions with chromatin and other companion TFs during development are poorly understood. To analyze such interactions in vivo, we profiled several TFs across a time course of human embryonic stem cell differentiation via CUT&RUN epigenome profiling, and studied their interactions with nucleosomes and co-occurring TFs by Enhanced Chromatin Occupancy (EChO), a computational strategy for classifying TF binding characteristics across time and space. EChO shows that at different enhancer targets, the same TF can employ either direct DNA binding, or “pioneer” nucleosome binding to access them. Pioneer binding is correlated with local binding of other TFs and enhancer motif character, including degeneracy at key bases in the pioneer factor target motif. Our strategy reveals a dynamic exchange of TFs at enhancers across developmental time that is aided by pioneer nucleosome binding.

overall_design: We used Cleavage under targets and Release using nuclease (Cut-and-Run), a chromatin profiling strategy in which antibody-targeted controlled cleavage by micrococcal nuclease releases specific protein-DNA complexes into the supernatant for paired-end DNA sequencing.

middle: P

first: Derek

middle: H

last: Janssens

first: Steven

last: Henikoff


title: Barley CI 16151 and fast-neutron-derived, immune-compromised mutants infected with the powdery mildew fungus (Blumeria graminis f. sp. hordei; isolate 5874)

status: Public on May 29 2018

city: Ames

first: Roger

last: Wise

address: 4201 ATRB, 2213 Pammel Drive

department: Plant Pathology & Microbiology (Iowa State University)

institute: USDA-ARS, Corn Insects and Crop Genetics Research Unit

summary: Purpose: The powdery mildew fungus, Blumeria graminis, is an obligate biotrophic pathogen of cereals and has significant impact on food security (Dean et al., 2012). B. graminis f. sp. hordei (Bgh) is the causal agent of powdery mildew on barley (Hordeum vulgare L.). We sought to address the temporal regulation of membrane trafficking associated gene expression in barley-powdery mildew interactions. We created an isogenic panel of immune signaling mutants to address three main questions: (i) which Blumeria secreted proteins are differentially regulated in response to different compromised genotypes, (ii) which barley membrane trafficking genes are altered in response to pathogen attack, and (iii) how are these genes interacting across genotypes and infection stages.

sample_organism:
Hordeum vulgare
Blumeria hordei

platform_organism:
Hordeum vulgare
Blumeria hordei

overall_design: 90 samples analyzed = 5 genotypes * 6 time points * 3 replications

first: Priyanka

last: Surana

first: Gregory

last: Fuerst


title: Expression changes in YUMM1.7 melanoma with/without PD-L2 overexpression under BRAFi treatment in NSG mice [Y1.7.FPKM.batch4]

status: Public on Sep 12 2017

city: Los Angeles

first: Willy

last: Hugo

state: California

address: 10833 Le Conte Ave

department: Medicine

institute: University of California, Los Angeles

summary: Treatment of advanced V600BRAF mutant melanoma using a BRAF inhibitor (BRAFi) or its combination with a MEKi typically elicits partial responses. We compared the transcriptomes of patient-derived tumors regressing on MAPKi therapy against MAPKi-induced temporal transcriptomic states in human melanoma cell lines or murine melanoma in immune-competent mice. Despite heterogeneous dynamics of clinical tumor regression, residual tumors displayed highly recurrent transcriptomic alterations and enriched processes, which were also observed in MAPKi-selected cell lines (implying tumor cell-intrinsic reprogramming) or in bulk mouse tumors (and the CD45-negative or -positive fractions,, implying tumor cell-intrinsic or stromal/immune alterations, respectively). Tumor cell-intrinsic reprogramming attenuated MAPK-dependency, while enhancing mesenchymal, angiogenic and IFN-inflammatory features and growth/survival dependence on multi-RTKs and PD-L2. In the immune compartment, PD-L2 upregulation in CD11c+ immunocytes drove the loss of T-cell inflammation and promoted BRAFi resistance. Thus, residual melanoma early on MAPKi therapy already displays potentially exploitable adaptive transcriptomic, epigenomic, immune-regulomic alterations.

overall_design: YUMM1.7 melanoma tumors in NOD/SCID mice with and without PD-L2 expression in baseline (vehicle treated) and BRAFi resistance were sent for transcriptomic analysis by single end 1x50bp HiSeq 3000 RNAseq analysis

first: Chunying

last: Song

first: Marco

last: Piva

first: Lu

last: Sun

first: Aayoung

last: Hong

first: Gatien

last: Moriceau

first: Xiangju

last: Kong

first: Hong

last: Zhang

first: Shirley

last: Lomeli

first: Jin

last: Qian

first: Clarissa

middle: C

last: Yu

first: Robert

last: Damoiseaux

first: Mark

last: Kelley

first: Kimberley

last: Dahlman

first: Philip

middle: O

last: Scumpia

first: Jeffrey

last: Sosman

first: Douglas

last: Johnson

first: Antoni

last: Ribas

middle: S

last: Lo


title: Expression changes in CD45neg subpopulation of YUMM1.7 melanoma pre MAPKi treatment vs. on MAPKi treatment [Y1.7.FPKM.batch3]

first: Willy

last: Hugo

overall_design: Sorted CD45- cells from YUMM1.7 melanoma tumors in C57BL/6 mice before treatment, during treatment with MAPKi were sent for transcriptomic analysis by single end 1x50bp HiSeq 3000 RNAseq analysis

first: Chunying

last: Song

last: Piva

first: Roger


title: Expression changes in Melanomas pre MAPKi treatment vs. on MAPKi treatment [Y1.7.FPKM.batch1.2]

status: Public on Sep 13 2017

overall_design: YUMM1.7 melanoma tumors in C57BL/6 mice before treatment, during treatment with MAPKi were sent for transcriptomic analysis by paired end 2x100bp HiSeq 2000 RNAseq analysis

first: Marco

first: Lu

last: Sun

first: Aayoung

last: Hong

last: Moriceau


title: Exploiting drug addiction mechanisms to select against MAPKi resistant melanoma

status: Public on Nov 28 2017

summary: Melanoma resistant to MAPK inhibitors (MAPKi) displays loss of fitness upon experimental MAPKi withdrawal and, clinically, may be resensitized to MAPKi therapy after a drug holiday. Here, we uncovered and therapeutically exploited the mechanisms of MAPKi addiction in MAPKi-resistant BRAF MUT or NRAS MUT melanoma. MAPKi-addiction phenotypes evident upon drug withdrawal spanned transient cell-cycle slowdown to cell-death responses, the latter of which required a robust phosphorylated ERK (pERK) rebound. Generally, drug withdrawal–induced pERK rebound upregulated p38–FRA1–JUNB–CDKN1A and downregulated proliferation, but only a robust pERK rebound resulted in DNA damage and parthanatos-related cell death. Importantly, pharmacologically impairing DNA damage repair during MAPKi withdrawal augmented MAPKi addiction across the board by converting a cell-cycle deceleration to a caspase-dependent cell-death response or by furthering parthanatos related cell death. Specifically in MEKi-resistant NRAS MUT or atypical BRAF MUT melanoma, treatment with a type I RAF inhibitor intensified pERK rebound elicited by MEKi withdrawal, thereby promoting a cell death–predominant MAPKi-addiction phenotype. Thus, MAPKi discontinuation upon disease progression should be coupled with specific strategies that augment MAPKi addiction.

overall_design: BRAF/MEK inhibitors resistant cell lines M249DDR5 and SKMEL28DDR1 were assayed for their responses after 6 hr of BRAF/MEK inhibitor treatment and after inhibitors withdrawal (by washin) for 6 and 24 hours

first: Gatien

last: Lomeli

first: Sheri

last: Holmen

first: Norman

last: Sharpless


title: Expression changes in melanoma cell lines under BRAFi treatment timepoints [RNA-Seq.CellLine.batch4]

overall_design: Paired melanoma cell lines before treatment and during BRAFi treatment were sent for transcriptomic analysis by single end 1x50bp RNAseq analysis

first: Xiangju

last: Kong

first: Hong

last: Zhang

first: Shirley

first: Jin

last: Qian

first: Clarissa

last: Yu

last: Damoiseaux


title: Expression changes in MAPKi resistant M229 melanoma lines co-cultured with PD-1 overexpressing HEK293T cells [CellLine.FPKM.batch5]

overall_design: M229 SDR and DDR lines cocultured with PD-1/GFP-control expressing HEK293T cells and with/without staurosporine treatment were sorted to yield purified melanoma population which were sent for transcriptomic analysis by single end 1x50bp HiSeq3000 RNAseq analysis

first: Robert

first: Mark

last: Kelley

first: Kimberley

last: Dahlman

first: Philip

last: Scumpia

first: Jeffrey

last: Sosman

last: Johnson


title: Molecular Signatures of Muscle Rehabilitation After Limb Disuse

status: Public on Aug 31 2017

city: Washington

first: Yi-Wen

last: Chen

state: DC

address: 111 Michigan Ave NW

institute: Children's Research Institute

summary: We have identified the molecular (transcriptional) signatures associated with muscle remodeling in response to rehabilitation in a patient cohort. Subjects with a closed malleolus fracture treated conservatively with 6 weeks of cast immobilization are recruited. Then subjects are enrolled in a 6 weeks structured rehabilitation program focusing on progressive resistance training of the ankle plantar flexor muscles. Phenotypic measurements are performed before (pre-rehab), during (mid-rehab, 3 weeks) and immediately after (post-rehab, 6 weeks) the rehabilitation intervention. The maximal cross-sectional area (muscle size) and peak torque (muscle strength) are quantified using isometric and isokinetic tests in combination with 3D-magnetic resonance imaging. Ankle plantar flexor muscle size and strength measurements are also performed on the uninvolved limb (serves as a control) at 4 months post-immobilization. Measurements are also acquired from the contralateral leg, which serves as an internal control.

overall_design:
Four longitudinal muscle biopsies are taken from the medial gastrocnemius of each subject and expression profiled over the entire human genome (U133 plus2). Muscle biopsies are taken at the following time points: before (pre-rehab; post-immobilization), after 3 weeks of rehabilitation (early transcriptional changes) and immediately after 6 weeks of rehabilitation (chronic transcriptional changes). An additional muscle biopsy is taken at 4 months post-immobilization from the uninvolved (contralateral) medial gastrocnemius, which serves as a control sample.
The subjects are grouped based on their % change of MRI with 6% as the cutoff value.

Immobolization: high responders- AFX006, AF007, AFX015, AFX017, AFX020, AFX022, AFX023, AFX024
low responders- AFX012, AFX013, AFX019, AFX021
Rehabilitation: high responders- AFX006, AFX007, AFX015, AFX016, AFX017, AFX020, AFX022, AFX023, AFX024
low responders- AFX009, AFX010, AFX011, AFX012, AFX013, AFX019, AFX021


title: Transcriptome analysis of HSPCs and T cells from aplastic anemia (AA) and healthy donors

status: Public on Mar 31 2021

first: Caiying

last: Zhu

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


title: Expression changes in Melanomas pre MAPKi treatment vs. on MAPKi treatment (Affymetrix)

status: Public on Sep 05 2017

first: Willy

last: Hugo

overall_design: Melanoma biopsies pre and on MAPKi treatment were sent for transcriptomic analysis using Affymetrix HuGene 1.0 microarray

first: Chunying

last: Song

first: Marco

last: Piva

first: Lu

last: Sun

last: Hong

first: Kimberly

first: Douglas

first: Antoni

last: Ribas

first: Roger

last: Lo


title: Expression changes in Melanomas pre MAPKi treatment vs. on MAPKi treatment (RNA-seq_Patient.batch3)

status: Public on Sep 08 2017

overall_design: Paired melanoma biopsies before and during MAPKi treatment were sent for transcriptomic analysis by paired end 2x150bp HiSeq3000 RNAseq analysis

first: Aayoung

first: Gatien

last: Moriceau

first: Xiangju

last: Kong

first: Hong

last: Zhang

first: Shirley

last: Lomeli

first: Jin

last: Qian


title: Expression changes in melanoma cell lines pre MAPKi treatment vs. post-MAPKi resistance (RNA-seq_CellLine.batch2)

overall_design: Paired melanoma cell lines before treatment and after MAPKi resistance were sent for transcriptomic analysis by paired end 2x50bp RNAseq analysis

first: Clarissa

last: Yu

first: Robert

last: Damoiseaux

first: Mark

last: Kelley

first: Kimberley

last: Dahlman

first: Philip

last: Scumpia

first: Jeffrey


title: Gene expression profiles in rat alveolar macrophages exposure to exfoliated graphene

status: Public on Jun 20 2017

first: Katsuhide

last: Fujita

summary: To further development of our gene expression approach to assess the effects of manufactured nanomaterials at the transcriptional level, we have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to distinguish characterization of physicochemical properties of exfoliated graphene (EGr).

overall_design: Exfoliated graphene (EGr) induced gene expression in rat alveolar macrophages were measured at 24 hours exposure to doses of 0.01mg/mL. The experiments were performed using control for each experiment (n=4).

first: Sawae

last: Obara


title: Expression changes in melanoma cell lines under BRAFi treatment timepoints [RNA-Seq.CellLine.batch3]

first: Willy

last: Hugo

overall_design: Paired melanoma cell lines before treatment and during BRAFi treatment were sent for transcriptomic analysis by paired end 2x150bp RNAseq analysis

first: Chunying

last: Song

first: Marco

last: Piva

first: Lu

last: Sosman

first: Douglas

last: Johnson


title: DOT1L inhibition with EPZ-5676 in human articular chondrocytes from 5 non-OA hip fracture patients

status: Public on Apr 20 2017

city: Leuven

first: Rekin's

last: Janky

address: Herestraat 49 Box 816

department: Nucleomics Core

institute: VIB

summary: To identify DOT1L targets, associated signaling pathways and networks in chondrocytes, we used genome-wide gene expression microarray analysis in human articular chondrocytes of 5 different donors (without known or documented joint disease) treated with EPZ-5676 or vehicle for 4 days. It is known that DOT1L inhibitors require longer time of treatment in order to show effect and influence the expression of MLL target genes in leukemia cells, but we opted for this relatively short inhibition time to be able to identify early changes induced by DOT1L inhibition.

overall_design: Human articular chondrocytes were obtained from 5 non-OA hip fracture patients. The cells were treated with 3 μM EPZ-5676 or vehicle (DMSO) for 4 days.

first: Silvia

last: Monteagudo

first: Frederique

last: Cornelis

first: Carolina

last: Aznar-Lopez

first: Ploi

last: Yibmantasiri

first: Frederic

last: Cailotto

first: Rik

last: Lories


title: Expression changes in Melanomas pre MAPKi treatment vs. on MAPKi treatment (RNA-seq)

overall_design: Paired melanoma biopsies/cell lines before treatment, during treatment and after resistance to MAPKi were sent for transcriptomic analysis by paired end 2x100bp HiSeq 2000 RNAseq analysis

last: Sun

first: Aayoung

last: Hong

first: Gatien

last: Moriceau

first: Xiangju

last: Kong

first: Hong

last: Zhang

first: Shirley

last: Lomeli

first: Jin

last: Qian

first: Clarissa

last: Yu

first: Robert

last: Damoiseaux

first: Mark

last: Kelley

first: Kimberly

first: Antoni

last: Ribas

first: Roger

last: Lo


title: RNA-Seq Analysis of Dose-Dependent TCDD-Elicited Jejunal Gene Expression in Male Mice

status: Public on Feb 28 2017

first: Timothy

last: Zacharewski

state: Michigan

address: 603 Wilson Road

department: BMB

summary: Dose-dependent jejunal gene expression was examined following repeated exposure (every 4 days for 28 days) to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). These data were used to examine the effect of repeated TCDD exposure on gene expression in the intestinal epithelium of C57BL/6 male mice.

overall_design: Three biological replicates for each dose (0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30) of TCDD and sesame oil vehicle

first: Kelly

last: Fader

first: Rance

last: Nault


title: RNA-Seq Analysis of Dose-Dependent TCDD-Elicited Ileal Gene Expression in Male Mice

summary: Dose-dependent ileal gene expression was examined following repeated exposure (every 4 days for 28 days) to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). These data were used to examine the effect of repeated TCDD exposure on gene expression in the intestinal epithelium of C57BL/6 male mice.


title: Expression changes in Melanomas pre MAPKi treatment vs. on MAPKi treatment

first: Willy

last: Hugo

overall_design: Refer to individual Series


title: Analysis of chromatin accessibility in human epidermis identifies putative barrier dysfunction-sensing enhancers

status: Public on Aug 28 2017

first: Matthew

last: Weirauch

state: Ohio

summary: To identify putative gene regulatory regions that respond to epidermal injury, we mapped chromatin dynamics in a stratified human epidermis during barrier maturation and disruption. Engineered skin substitutes (ESS) cultured at the air-liquid interface were used as a model of developing human epidermis with incomplete barrier formation. The epidermal barrier stabilized following engraftment onto immunocompromised mice, and was compromised again upon injury. Modified formaldehyde-assisted isolation of regulatory elements (FAIRE) was used to identify accessible genomic regions characteristic of monolayer keratinocytes, ESS in vitro, grafted ESS, and tape-stripped ESS graft. We mapped differentiation- and maturation-associated changes in transcription factor binding sites enriched at each stage and observed overrepresentation of AP-1 gene family motifs in barrier- deficient samples. Transcription of TSLP, an important effector of immunological memory in response to allergen exposure, was dramatically elevated in our barrier-deficient samples. We identified dynamic DNA elements that correlated with TSLP induction and may contain enhancers that regulate TSLP. Two dynamic regions were located near the TSLP promoter and overlapped with allergy-associated SNPs rs17551370 and rs2289877, strongly implicating these loci in the regulation of TSLP expression in allergic disease. Additional dynamic chromatin regions ~250kb upstream of the TSLP promoter were found to be in high linkage disequilibrium with allergic disease SNPs. Taken together, these results define dynamic chromatin accessibility changes during epidermal development and dysfunction.

overall_design: FAIRE-seq performed on primary keratinocytes, stratified engineered skin substitute (ESS), ESS grafted onto a nude mouse, and Grafted ESS that had undergone tape-stripping. 4-6 replicates were used for each.

first: Julie

last: Lander

first: Raphael

last: Kopan


title: RNAseq changes in mouse wound with or without time course treatment by Vemurafenib

status: Public on Jul 29 2016

summary: BRAF inhibitors are highly effective therapies for patients with BRAF V600 mutated metastatic melanoma. Patients who receive BRAF inhibitors develop a variety of hyper-proliferative skin conditions, whose pathogenic basis is the paradoxical activation of the mitogen-activated protein kinase (MAPK) pathway in BRAF wild-type cells. Most of these hyper-proliferative skin changes improve when a MEK inhibitor is co-administered, as a MEK inhibitor blocks paradoxical MAPK activation. We tested whether we could take advantage of the mechanistic understanding of the skin hyper-proliferative side effects of BRAF inhibitors to accelerate skin wound healing by inducing paradoxical MAPK activation. Here we show that the BRAF inhibitor vemurafenib accelerates human keratinocyte proliferation and migration by increasing ERK phosphorylation and cell cycle progression. Topical treatment with vemurafenib in two wound-healing models in mice accelerated cutaneous wound healing and improved the tensile strength of healing wounds through paradoxical MAPK activation; addition of a MEK inhibitor reversed the benefit of vemurafenib-accelerated wound healing. The same dosing regimen of topical BRAF inhibitor did not increase the incidence of cutaneous squamous cell carcinomas in mice even after the application of a carcinogen. Therefore, topical BRAF inhibitors may have clinical applications in accelerating the healing of skin wounds.

overall_design: Full depth incisional wound mice tissues with/without Vemurafenib treatment were sent for RNAseq analysis on day 2, 6 and 14

first: Helena

last: Escuin-Ordinas

first: Shuoran

last: Li

first: Lu

last: Sun

first: Michael

last: Xie

first: Rong

last: Huang

first: Jing

last: Jiao

first: Felipe

last: Meira de-Faria

first: Susan

last: Realegeno

first: Paige

last: Krystofinski

first: Ariel

last: Azhdam

first: Sara

last: Komenan

first: Mohammad

last: Atefi

first: Begoña

last: Comin-Anduix

first: Matteo

last: Pellegrini

first: Alistair

last: Cochran

middle: L

last: Modlin

first: Harvey

last: Herschman

first: William

last: McBride

first: Tatiana

last: Segura