title: Extensive changes in transcriptomic “fingerprints” and immunological cells in the large organs of patients dying of acute septic shock and multiple organ failure caused by Neisseria meningitidis

status: Public on Jan 14 2020

city: Oslo

first: Berit

middle: Sletbakk

last: Brusletto

address: Kirkeveien 166

department: Oslo University Hospital

country: Norway

institute: Medical Biochemisty

summary:
Background: Patients developing meningococcal septic shock reveal very high levels of Neisseira meningitidis and endotoxin in the circulation and organs, leading to acute cardiovascular, pulmonary and renal failure, coagulopathy and a high case fatality rate within 24 hours.
Objective: To investigate transcriptional profiles in heart, lungs, kidneys, liver and spleen and immunostain key inflammatory cells and proteins in post mortem formalin-fixed, paraffin-embedded (FFPE) tissue samples from meningococcal septic shock patients.
Patients and methods: Total RNA was isolated from FFPE and fresh frozen (FF) tissue samples from five patients and two controls (non-inflammatory disease). Differential expression of genes was detected using Affymetrix GeneChip Human Transcriptome 2.0 Arrays. Lung and heart tissue samples were immunostained for T-and B cells, macrophages, neutrophils and the inflammatory markers Plasminogen activator inhibitor-1 (PAI-1) and Monocyte chemoattractant protein 1 (MCP-1). Inflammatory mediators were quantified in lysates from FF tissues.
Results: The transcriptional profiles showed significant regulation of pathways associated with organismal death, cell death and survival, leukocyte migration, cellular movement, proliferation of cells, cell-to-cell signaling, immune cell trafficking and inflammatory responses in an organ-specific clustering manner. The canonical pathways including acute phase response-, EIF2-, TREM1-, IL-6-, HMBG1-, PPAR signaling and LXR/RXR activation were associated with acute heart, pulmonary and renal failure and with inflammatory changes in liver and spleen were identified. The main upstream regulators were TNF, IL-1β, IL-6, RICTOR, miR-6739-3p and CD3. Increased numbers of inflammatory cells (CD68+, MPO+, CD3+ and CD20+) were found in lungs and heart. PAI-1 inhibiting fibrinolysis and MCP-1 attracting leukocyte were found significantly present in the septic tissue samples compared to the controls.
Conclusions: Hundreds of transcripts were altered in lungs, heart and kidneys, all organs with an acute dysfunction. Relatively fewer transcripts were changed in the spleen. Certain transcripts were associated with the number of. N. meningitidis in the tissues. We identified specific biomarker panels which differed from organ to organ. Our results highlight the complexity of gene regulation in the different tissues. Future treatment strategies blocking or stimulating only one molecule or pathway appear unlikely to succeed.

overall_design: Reference : Meningococcal septic shock (MSS) patients (N=5 patients with FFPE tissue and from 3 of the same patients FF tissue (n=3)), from each patient tissue samples from lungs, heart, kidneys, liver, spleen. Control patients (N=2) with acute non-infectious death. FFPE tissue samples from lungs, heart, kidneys, liver, spleen.

middle: S

first: Else

middle: M

last: Løberg

first: Bernt

last: Hellerud

first: Ingeborg

last: Goverud

first: Jens

middle: P

last: Berg

first: Ole

middle: K

last: Olstad

first: Unni

last: Gopinathan

first: Petter

last: Brandtzaeg

first: Reidun

last: Øvstebø


title: TAK-418-418, a LSD1 inhibitor, can rescue the genome wide chromatin abnormality in hippocapmus tissue in KMT2D+/bGeo mice  after 2 week treatment [ChIP-seq]

status: Public on Mar 11 2020

city: Ellicott city

first: Li

last: Zhang

state: Maryland

address: 733N Broadway

department: Department of Human Genetics

country: USA

institute: The Johns Hopkins University

type: Genome binding/occupancy profiling by high throughput sequencing

summary: KMT2D+/bGeoation in KMT2D, a histone-lysine N-methyl transferase, is responsible for majority of Kabuki syndrome in human. A mouse model of Kabuki syndrome with heterzygous KMT2D+/bGeoation of KMT2D, KMT2D+/bGeo was created to understand the disease mechanism and for drug discovery. TAK-418-418, a lysine-specific histone demethylase (LSD1) inhibitor, was tested on these mice for therapeutic treatment of the disease. Rescue of genome wide chromatin abnormality, which has been reported in KMT2D+/bGeo mice, was evaluated by high throughput next generation sequencing following chromatin immunoprecipitation of H3K4me1 and H3K4me3.

overall_design: Wild type mice and KMT2D+/bGeo mice were treated with either TAK-418-418 (3-4 per group) or vehicle control (3-4 per group) starting at age of 2-week  old. Hippacampi were harvested at the end of 2-week treatment. Global chromatin changes were investigated by high throughput CHIPSEQ of H3K4me1 and H3K4me3.

first: Hans

middle: T

last: Bjornsson


title: Expression data from tumor lungs after continuous vs. pulsatile selumetinib treatment in KRASG12C GEMM

status: Public on Sep 11 2019

city: Spring House

first: Hyejin

last: Choi

state: PA

address: 1400 McKean Rd

institute: Johnson & Johnson

summary:
KRAS is one of the driver oncogenes in non-small cell lung cancer (NSCLC), but remains refractory to current modalities of targeted pathway inhibition, which include inhibiting downstream kinase MEK to circumvent KRAS activation. Here, we show that pulsatile, rather than continuous, treatment with MEK inhibitors (MEKis) maintains T cell activation and better control tumor growth and survival.
We used microarrays to examine the MAPK signaling pathway suppression from tumor lungs of KRASG12C GEMM after continuous vs. pulsatile treatment of selumetinib.

overall_design: Tumor was induced by intranasal administration of adenoviral-Cre to KRASLSL-G12C/+ GEMM mice. Once the tumor size reached approximately 500 mm3 (at about 12 weeks after adenoviral inoculation), KRASG12C GEMM mice were treated with selumetinib continuously (daily for 3 weeks, 25mg/kg, BID) or pulsatilely (1 cycle: 1 week ON + 1 week OFF, total 3 cycles, 25mg/kg, BID) with their matched control (vehicles), since the treatments were not done at the same time. The mice were sacrificed after selumetinib treatment is completed.

first: Deng

last: Jiehui

last: Shuai

first: Kwok

last: Wong

first: Jedd

middle: D

last: Wolchok

first: Taha

last: Merghoub


title: Increased sulfation of bile acids in mice and human subjects with sodium taurocholate cotransporting polypeptide deficiency

status: Public on Jun 13 2019

city: Beijing

first: Wenhui

last: Li

address: 7 Science Park Road ZGC Life Science Park

country: China

institute: National Institute of Biological Sciences

type: Expression profiling by high throughput sequencing

summary:
Purpose: To decipher the biochemical basis for the declining of total bile acids (TBA) levels in the late age of Slc10a1-/- mice, we performed a serial liver RNA-Seq analysis of mRNA expression with male mice at different ages.

Methods: Liver mRNA profiles of 4-week, 8-week, 20-month-old wild-type (WT) and sodium taurocholate cotransporting polypeptide knockout (Slc10a1-/-) mice were generated by deep sequencing, in triplicate, quadruplicate or sextuplicate, using  Illumina Hiseq-2500 platform. Clean mRNA-seq reads were aligned to the mouse reference genome (GRCm38) with TopHat (v2.0.13), guided by Ensembl gene annotation v83. Only uniquely aligned and properly paired reads were retained for further analysis. Gene-level read counts were calculated with HTseq (v0.6.1p1) with the union mode. Genes with less than a total of 11 non-normalized reads across all samples were excluded. Data normalization and statistical analysis of differential expression were performed with the DEseq2 (v1.10.0) R package. Pair-wise Spearman correlation between samples across all quantified genes used for hierarchical clustering.

Results: At 4 weeks and 8 weeks, WT and Slc10a1-/- mice exhibited clear different pattern in terms of transcriptome similarity and were well separated, however, the difference was indistinguishable at 20 months.And changes of pathways involved in the metabolism of xenobiotics in Slc10a1-/- mice.

Conclusions: Our study reveal that enhanced BA sulfation is a major mechanism for BA detoxification and elimination in Slc10a1-/- mice with hypercholanemia.

first: Hanqing

last: Zhao


title: RNA sequencing to identify NPR-8-regulated genes in C. elegans defense against pathogen infection

status: Public on Oct 15 2019

city: Spokane

first: Yiyong

last: Liu

state: WA

address: 412 E Spokane Falls Blvd

institute: Washington State University

summary: To gain molecular insights on how NPR-8 regulates C. elegans defense against pathogen infection, we used RNA sequencing to profile gene expression in npr-8(ok1439) animals relative to wild-type animals with or without P. aeruginosa infection.  We found that NPR-8 suppresses the expression of genes related to cuticle structure activity including collagen genes, and lack of NPR-8-mediated suppression in npr-8(ok1439) animals contributes to their improved survival against P. aeruginosa infection.

overall_design: Five replicates of four groups of RNA samples (npr-8(ok1439) and wild-type animals with or without exposure to P. aeruginosa for 24 hrs) were sequenced.  Gene expression was compared between groups to identify NPR-8-regulated genes under uninfection or infection conditions.

first: Durai

last: Sellegounder

first: Jingru

last: Sun


title: ChIP-seq in human tonsilar Naïve and Germinal Center B cells and DLBCL cell lines

status: Public on Jan 16 2019

city: New York

first: Ashley

middle: Stephen

last: Doane

state: NY

address: 1300 York Ave

institute: Weill Cornell Medicine

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

overall_design: Refer to individual Series


title: Long non-coding RNAs discriminate the stages and gene regulatory states of the human humoral immune response (RNA-Seq)

status: Public on Jan 15 2019

first: Cem

last: Meydan

state: New York

address: 1305 York

department: Physiology & Biophysics

institute: Weill Cornell Medical College

type: Non-coding RNA profiling by high throughput sequencing

summary: Long non-coding RNAs (lncRNAs) make up a vast majority of the human transcriptome and have key regulatory functions. We performed unbiased de novo annotation of transcripts expressed during the humoral immune response in humans. Remarkably, 30% of the total human genome is transcribed during this process, and yet 58% of these transcripts manifest striking differential expression indicating phylogenetic relationships among cell types that is even more robust than coding genes. We provide a regulatory atlas of lncRNAs in naïve B and GC B-cells that indicates their partition into ten functionally distinct categories based on chromatin features including H3K4me1, H3K4me2, H3K4me3, H3K27ac, H3K27me3, DNase hypersensitivity, CTCF, EP300, CREBBP, MED1, BRD4, FOXO1 and FOXP1 localization. This procedure defined lncRNAs classes such as enhancer RNA (eRNA), bivalent lncRNA, and CTCF associated, among others. eRNAs are transcribed in 8.6% of regular enhancers and 36.5% of super enhancers, associated with coding genes that participate in critical immune regulatory pathways. Plasma cells uniquely featured high levels of circular RNAs accounted for by and reflecting the combinatorial clonal state of the Immunoglobulin loci.

overall_design: Detection and funtional study of novel and annotated expressed lncRNAs during human humoral immune response

first: Xabier

last: Agirre

first: Yanwen

last: Jiang

first: Leire

last: Garate

first: Zhuoning

first: Akanksha

last: Verma

first: Bruno

last: Paiva

first: José

middle: I

last: Martín-Subero

first: Olivier

last: Elemento

first: Christopher

middle: E

last: Mason

first: Felipe

last: Prosper

first: Ari

last: Melnick


title: Transcriptome and sRNA profiling of Maize dcl5 CRISPR null alleles

status: Public on Dec 17 2018

city: Davis

first: Blake

middle: C.

last: Meyers

state: CA

address: 451 Health Sciences Dr.

department: UC Davis Genome Center

institute: University of California - Davis

summary: Small RNAs play important roles during plant development by regulating transcript levels of target mRNAs, maintaining genome integrity, and reinforcing DNA methylation. Dicer-like 5 (Dcl5) is proposed to be responsible for precise slicing to generate diverse 24-nt phased, secondary small interfering RNAs (phasiRNAs), which are exceptionally abundant in meiotic anthers of maize, rice, and other grasses 1. Importance and functions of these phasiRNAs remain unclear. Here we used the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) Cas9 system to mutate Dcl5. We report that dcl5 mutants have few or no 24-nt phasiRNAs, develop short anthers and defective tapetal cells, and exhibit temperature-sensitive male fertility. We propose that DCL5 and 24-nt phasiRNAs are critical for fertility under growth regimes for optimal yield.

overall_design: RNA and sRNA-seq libraries were made from meiotic anthers of multiple Maize dcl5 null alleles along with the fertile siblings.

first: Chong

last: Teng

first: Han

last: Zhang

first: Reza

last: Hammond

first: Sandra

last: Mathioni

middle: C

first: Virginia

last: Walbot


title: Transcriptomic profiling of E9.5 mouse embryos lacking the lipoprotein receptor SR-B1

status: Public on Sep 21 2018

city: Santiago

first: Dolores

last: Busso

address: Alameda 340 Edificio CIM-Patio 4 piso

department: Nutrition, Diabetes and Metabolism

country: Chile

institute: Pontificia Universidad Católica de Chile

summary: The high-density lipoprotein receptor SR-B1 mediates cellular uptake of several lipid species, including cholesterol and vitamin E. During early development, SR-B1 is located in the maternal-fetal interface, where it facilitates vitamin E transport towards the embryo. Consequently, embryos lacking SR-B1 are vitamin E-deficient, and around half of them fail to close the neural tube and show neural tube defects (NTD). Here, we studied the transcriptomic profile of mouse embryos lacking SR-B1 to identify the molecular determinants of this phenotypic difference. We used RNA-Seq to analyze the expression of mRNA globally in E9.5 wild-type embryos and embryos lacking SR-B1 with or without NTD, in order to compare expression profiles in those groups and to identify putative genes driving phenotypic differences.

overall_design: We analyzed 3 samples of each group (wild-type, SR-B1 KO normal, SR-B1 KO NTD). Each samples corresponded to a pool of 3 embryos.

first: Nicolas

last: Santander

first: Carlos

last: Lizama


title: Comprehensive gene expression analysis of mouse brains in postnatal maturation stages using Transcriptome Tomography

status: Public on Aug 07 2018

city: Wako-shi

first: Yuko

last: Okamura-Oho

state: Saitama

address: 2-1, Hirosawa

country: Japan

institute: RIKEN


title: Gene expression profiling of the whole mouse brain at 3 weeks of post-natal age using transcriptome tomography

summary: We developed a novel framework to assess comprehensive endogenous gene expression maps in a broad and isotropic 3D-anatomical context using a relatively small number of original data points: transcriptome tomography. Using this method, we produced a dataset of gene expression maps of the whole mouse brain at 3 weeks after birth, computationally reconstructed from fraction data.

overall_design: A total of 28 fraction samples obtained with body axes-based slicing preparation conjugated with anatomical image acquisition were analysed. There are a sets of body axes-based preparation series: the S series composed of10 fractions/ C of 12 fractions/ H of 6 fractions.

first: Y

first: H

last: Yokota


title: Gene expression profiling of the whole mouse brain at 7 days post-natal age using transcriptome tomography

summary: We developed a novel framework to assess comprehensive endogenous gene expression maps in a broad and isotropic 3D-anatomical context using a relatively small number of original data points: transcriptome tomography. Using this method, we produced a dataset of gene expression maps of the whole mouse brain at 7 days after birth, computationally reconstructed from fraction data.

overall_design: A total of 22 fraction samples obtained with body axes-based slicing preparation conjugated with anatomical image acquisition were analysed. There are a sets of body axes-based preparation series: the S series composed of 6 fractions/ C of 10 fractions/ H of 6 fractions.


title: Gene expression profiling of the whole mouse brain at 3 days post-natal age using transcriptome tomography

summary: We developed a novel framework to assess comprehensive endogenous gene expression maps in a broad and isotropic 3D-anatomical context using a relatively small number of original data points: transcriptome tomography. Using this method, we produced a dataset of gene expression maps of the whole mouse brain at 3 days after birth, computationally reconstructed from fraction data.

overall_design: A total of 34 fraction samples obtained with body axes-based slicing preparation conjugated with anatomical image acquisition were analysed. There are a sets of body axes-based preparation series: the S series, composed of11 fractions/ C of 15 fractions/ H of 8 fractions.


title: Reconstitution of the human pancreatic niche stimulates differentiation of hESCs into beta cells and reveals new signals for pancreatic endocrine cell maturation

status: Public on Jun 01 2018

city: Houston

first: Malgorzata

last: Borowiak

address: 1 Baylor Plaza

institute: Baylor College of Medicine

summary: RNA-seq was performed for hESC-derived endocrine progenitors (EPs) treated with WNT5A for short-term (12h) and long-term (5 days) to investigate the downstream targets of WNT5A in EPs. Sequencing of untreated cells and those treated with WNT5A for 12h, which are at EP stage, and for 5 days, which are at beta cell stage, allowed for observation of developmental changes during in vitro differentiation.

overall_design:
Two controls as 12h or 5 days untreated (maintained in B27) and two 12h or 5 days WNT5A-treated EPs.

Grant ID: 2O19/33/B/NZ3/01226
Grant title: OPUS
Funding source: Polish National Science Center
Grantee: Dr. Malgorzata Borowiak

Grant ID: 2020/39/B/NZ3/01408
Grant title: OPUS
Funding source: Polish National Science Center
Grantee: Dr. Malgorzata Borowiak

Grant ID: POIR.04.04.00-00-20C5/16-00
Grant title: TEAM
Funding source: Foundation for Polish Science
Grantee: Dr. Malgorzata Borowiak

first: Diane

last: Yang

first: Jolanta

last: Chmieloweic

first: Marissa

middle: A

last: Scavuzzo


title: Transciptomic analysis of cachectic muscles from metastatic allograft models

status: Public on Jul 01 2018

first: Manoj

last: Kandpal

address: 1230 York Ave

department: Hospital Bioinformatics

institute: Rockefeller University

summary: RNA sequencing analysis of muscles comparing normal muscles with cachectic muscles isolated from mice bearing distant metastasis from C26m2 and 4T1 murine colon and breast cancer cell lines, collected at the onset of weight loss five weeks after tumor cell injection in these mice.

overall_design: Transcriptomic analysis of muscles performed by RNA sequencing (RNA seq) isolated from mice bearing metastatic colon cancer cell line, C26m2 or metastatic breast cancer cell line, 4T1 and their respective age-matched healthy controls. Mice bearing distant metastases were compared using the resection-and-relapse approach after 5 weeks post-tumor cell injection.

first: Swarnali

last: Acharyya

first: Gang

last: Wang

first: Anup

last: Biswas

first: Wanchao

last: Ma


title: Rice domestication-associated miRNA 397 targets laccases to facilitate lignin biosynthesis and yield-related traits [ncRNA-seq]

status: Public on Apr 25 2018

city: Bangalore

first: Shivaprasad

last: Padubidri V.

address: GKVK Campus, Bellary road

department: Plant epigenetics

country: India

institute: National Center for Biological Sciences

summary: MicroRNAs (miRNAs) are a class of 21 nt non-coding small RNAs (sRNAs) produced from endogenously expressed MIR genes. MiRNAs are mostly involved in development and disease resistance. To know the involvement of miRNAs during domestication of rice, sRNA sequencing of two wild species (O. nivara and O. rufipogon), one landrace (O. sativa chomala) and one cultivated species of rice (O. sativa indica Pusa Basmati-1) was carried out. Analysis of sRNA datasets revealed a surprisingly higher abundance of 22nt sRNAs originating from a loci on Chromosome 2 in wild rice species. This locus codes for a 22 nt miRNA named as miR397. Studies in Arabidopsis and O. sativa japonica nipponbare have shown that miR397 targets a group of proteins called laccases, which are involved in secondary metabolite (lignin) production. The expression of these targets also differs across the species shown through RNA-Seq analysis. Although a functional significance of this interaction between the miRNA and laccase has not been understood. In the current study we attempt to explain the functional relevance of the miRNA in domestication of rice.

sample_organism:
Oryza rufipogon
Oryza sativa
Oryza nivara
Oryza sativa Indica Group
Oryza sativa aus subgroup

overall_design: We have performed sRNA seq analysis using 4-week old seedling, flagleaf and panicle of various rice species. Libraries were prepared from total RNA isolated from the tissues mentioned.

first: Padubidri

middle: V

last: Shivaprasad

first: Swetha

last: Chenna


title: Rice domestication-associated miRNA 397 targets laccases to facilitate lignin biosynthesis and yield-related traits

platform_organism:
Oryza rufipogon
Oryza sativa
Oryza nivara
Oryza sativa Indica Group
Oryza sativa aus subgroup


title: Gene induction by the USP6 oncogene in response to interferon

status: Public on Jan 24 2018

city: Philadelphia

first: Ian

last: Henrich

address: 803D Abramason Research Center, 3615 Civic Center Blvd

institute: University of Pennsylvania

summary: We examined the role of the USP6 oncogene in the patient-derived immortalized ewing sarcoma cell line RD-ES. RNA-sequncing revealed that USP6 induces numerous genes that overlap with genes induced by interferon treatment. When USP6-expressing cells were treated with IFN, many of the overlapping genes were synergistically upregulated, indicating an overlap in signaling pathways.

overall_design: Examine the effects of USP6 and/or IFN on gene induction in RD-ES cells

first: Margaret

last: Chou


title: Epigenomic analysis of Atrx deficiency in murine glioma cells of orgin

status: Public on Dec 31 2017

first: Jason

last: Huse

state: TX

address: 1515 Holcombe Blvd

department: Department of Pathology

institute: University of Texas MD Anderson Cancer Center


title: Epigenomic analysis of Atrx deficiency in murine glioma cells of orgin [H3.3 ChIP]

summary: The chromatin regulator ATRX is inactivated in large subsets of adult and pediatric glioma.  Whether and how ATRX deficiency promotes oncogenesis by epigenomic dysregulation remains unclear.  We found that Atrx loss, especially when coupled with Tp53 inactivation, promoted cell motility and modulated differentiation state in primary murine neuroepithelial progenitors, recapitulating characteristic disease phenotypes and molecular features.  Moreover, Atrx deficiency induced widespread shifts in chromatin accessibility, histone composition, and gene transcription at vacant Atrx binding sites distributed across the genome.  Finally, target genes mediating Atrx-deficient phenotypes in vitro exhibited similarly selective misexpression in ATRX-mutant human glioma tissues and cell lines.  These findings demonstrate that, in appropriate physiological contexts, ATRX deficiency and its epigenomic sequelae are sufficient to induce disease-defining oncogenic phenotypes.

overall_design: Examination of H3.3 compositional changes genome-wide arising in the setting of Atrx deficiency in murine neuroepithelial progenitor cells (NPCs)

first: Carla

last: Danussi

first: Promita

last: Bose

first: Kasthuri

last: Kannan


title: Epigenomic analysis of Atrx deficiency in murine glioma cells of orgin [RNA-seq]

overall_design: Transcriptional analysis of Tp53+/+ and Tp53-/- neuroepithelial progenitor cells with and without Atrx inactivation


title: Epigenomic analysis of Atrx deficiency in murine glioma cells of orgin [ATAC-seq]

overall_design: Examination of chromatin accessibility changes acquired with Atrx deficiency in Tp53-/- neuroepithelial progenitor cells


title: Epigenomic analysis of Atrx deficiency in murine glioma cells of orgin [Atrx ChIP]

overall_design: Examination of ATRX binding sites in Tp53+/+ and Tp53-/- neuroepithelial progenitor cells (NPCs)


title: Newborn and young adult (2 months) mouse dorsal skin cell culture time-series RNA-Seq

status: Public on Sep 14 2017

city: Los Angeles

first: Mingxing

last: Lei

state: California

address: 2011 Zonal Ave HMR 304A

institute: University of Southern California

summary: Organoid formation is critical to the progress of regenerative medicine. We use the formation of skin organoids from dissociated cells to study the self-organization process. Here we live-image the process which reveals an unexpectedly complex morphogenetic process: dissociated cells – aggregates – polarized cysts – fused cysts– planar skin – hair placodes. Transcriptome profiling and functional testing show orderly expression peaks of adhesion molecules, insulin-like growth factors, Wnts, extracellular matrix molecules, and matrix metalloproteinases are crucial to the sequential morphological transitions. We draw an analogy between these self-organizing morphogenetic behaviours and the self-assembly of molecules in biophysics, with different morphological stages connected by phase transition-like switches. Adult cells, normally stalled as aggregates, can be restored to reform hairy skin by reactivation of the self-organization process with timely supply of molecular cues. Physical processes and molecular events may work in tandem to achieve organoid self-formation in tissue engineering and in vivo.

overall_design: Comparison of mRNA profiles in newborn and young adult (about 2 months) mouse dorsal skin reconstitution cells at different culture time points

first: Cheng-Ming

last: Chuong


title: The TroR transcription factor regulates iron homeostasis in the halophilic archaeon Haloferax volcanii

status: Public on Nov 16 2023

city: Durham

first: Amy

last: Schmid

state: NC

address: 125 Science Dr.

department: Biology

institute: Duke University


title: Transcriptome analysis of quorum sensing-dependent genes in Burkholderia gladioli BSR3.

status: Public on Aug 18 2017

city: Busan

first: Jungwook

last: Park

address: Pusan National University, 2, Busandaehak-ro 63beon-gil, Geumjeong-gu, Busan 609-735, Korea

department: Microbiology

country: South Korea

institute: Pusan National University

summary: In Burkholdeira gladioli BSR3, quorum sensing (QS) signal plays a pivotal role in many bacterial behaviors, including motility, toxin production and oxalogenesis. To understand transcriptional profiling of QS-dependent genes, we carried out RNA-Seq analysis of the wild type B. gladioli BSR3, and a QS-defective mutant under different culture states (10h and 24h after incubation), representing exponential phase and stationary phase.

overall_design: 2 samples examined: Burkholderia gladioli BSR3 wild type, and a QS-defective mutant, COK94 (BSR3 bglu_2g11050::lacZ). Two conditions: cultured in LB media for 10h or 24h.

first: Sunyoung

last: Kim

first: Young-Su

last: Seo


title: RNA sequencing analysis of the Lewis versus Brown Norway rat, with or without Toxoplasma gondii infection

status: Public on Jul 24 2017

city: Urbana

first: William

middle: Harold

last: Witola

state: Illinois

address: 2001 South Lincoln Avenue

department: Pathobiology

institute: University of Illinois at Urbana-Champaign

summary: Rats vary in their susceptibilities to Toxoplasma gondii infection depending on the rat strain. Compared to the T. gondii-susceptible Brown Norway (BN) rat, the Lewis (LEW) rat is extremely resistant to T. gondii. Thus, these two rat strains are ideal models for elucidating host mechanisms that are important for host resistance to T. gondii infection. Therefore, in an attempt to unravel molecular factors directing the protective early innate immune responses in the LEW rat, we performed RNA sequencing analysis of the LEW versus BN rat, with or without T. gondii infection.

overall_design: Total RNA was obtained from fresh peritoneal cells of LEW and BN rats (with or without T. gondii infection), 24 hours post-infection. RNA libraries were generated using the Illumina's 'TruSeq Stranded mRNAseq Sample Prep kit' (Illumina). The libraries were quantitated by fluorometry (Qubit), and their quality determined using a Bioanalyzer. The libraries were then diluted and quantified by qPCR. Sequencing of the RNA libraries was done using a HiSeq SBS sequencing kit version 4 and a HiSeq2500 system (Illumina). Residual adapter content and low quality bases on the generated sequences were trimmed using Trimmomatic (version 0.33), while the bcl2fastq v2.17.1.14 Conversion Software (Illumina) was used to generate and demultiplex Fastq files from the sequence data. ASCII offset of 33 known as Sanger scores were used to determine the quality scores line in fastq files. Feature Counts in the Sub-read (version 1.5.0) package were used to derive gene counts, while gene annotations, including gene ontology terms, were downloaded from Ensembl Release 84 for Rnor_6.0, and ToxoDB.org Release 28 for T. gondii GT1. Samtools (v. 1.3) idxstats tool was used to determine the number of reads mapping to each rat chromosome and to the T. gondii genome. By ANOVA, using a false discovery rate (FDR) of 0.05, genes’ expression patterns related to the four experimental groups (T. gondii-infected and uninfected LEW and BN rat groups; n = 4 per group) were generated with reads ranging from 13.1 – 18.3 million per sample that aligned uniquely within 32,662 rat genes and 8,637 T. gondii genes.

middle: H

first: Chi Yong

first: Xuejin

last: Zhang


title: Human RELA haploinsufficiency results in autosomal dominant chronic mucocutaneous ulceration: the transcriptional profile of RelA haploinsufficient patients

status: Public on May 09 2017

city: Boston

first: Janet

state: MA

address: 1 Blackfan Circle, Karp 10007D

department: Immunology

institute: Boston Children's Hospital

summary: The treatment of chronic mucocutaneous ulceration is challenging and only some patients respond selectively to inhibitors of tumor necrosis factor-alpha (TNF-a). TNF-a activates opposing pathways leading to caspase-8-mediated apoptosis as well as NF-kB-dependent cell survival. We investigated the etiology of autosomal dominant mucocutaneous ulceration in a family whose proband was dependent on anti-TNF-a therapy for sustained remission. A heterozygous mutation in RELA (NM_021975: c.559+1G>A), encoding the NF-kB subunit RelA (p65), segregated with the disease phenotype and resulted in RelA haploinsufficiency. The patients’ fibroblasts exhibited increased apoptosis in response to TNF-a, impaired NF-kB activation, and defective expression of NF-B-dependent anti-apoptotic genes. We show that Rela+/- mice have similarly impaired NF-kB activation, develop cutaneous ulceration from TNF-a exposure, and exhibit severe dextran sodium sulfate-induced colitis ameliorated by TNF-a inhibition. These findings demonstrate an essential contribution of biallelic RELA expression in protecting stromal cells from TNF-a-mediated cell death, thus delineating the mechanisms driving the effectiveness of TNF-a inhibition in this disease.

overall_design: Total RNA was obtained from human dermal fibroblasts from two patients with RelA haploinsufficiency  (in duplicates) as well as three healthy controls after they were treated with TNF-α for 24 hours and the transcriptional profile of the samples was determined.

first: Raif

last: Geha

first: Jeffrey

last: Goldsmith

first: Athos

last: Bousvaros

first: Toshiro

last: Ohsumi

first: Wayne

last: Bainter

first: Juan

last: Castillo

first: Fatma

last: Dedeoglu

first: Yousef

middle: R

last: Badran


title: Natural Selection has Shaped Coding and Non-coding Transcription in Primate CD4+ T-cells

status: Public on Dec 29 2016

city: Ithaca

first: Charles

middle: G

last: Danko

address: Hungerford Hill Rd

department: Baker Institute

institute: Cornell University

summary: Transcriptional regulatory changes have been shown to contribute to phenotypic differences between species, but many questions remain about how gene expression evolves.  Here we report the first comparative study of nascent transcription in primates.  We used PRO-seq to map actively transcribing RNA polymerases in resting and activated CD4+ T-cells in multiple human, chimpanzee, and rhesus macaque individuals, with rodents as outgroups.  This approach allowed us to directly measure active transcription separately from post-transcriptional processes.  We observed general conservation in coding and non-coding transcription, punctuated by numerous differences between species, particularly at distal enhancers and non-coding RNAs.  Transcription factor binding sites are a primary determinant of transcriptional differences between species.  We found evidence for stabilizing selection on gene expression levels and adaptive substitutions associated with lineage-specific transcription.  Finally, rates of evolutionary change are strongly correlated with long-range chromatin interactions.  These observations clarify the role of primary transcription in regulatory evolution.

sample_organism:
Macaca mulatta
Pan troglodytes
Homo sapiens
Mus musculus
Rattus norvegicus

overall_design: We analyzed collected PRO-seq data from CD4+ T-cells isolated from five mammalian species in two conditions.


title: Direct Isolation and Characterization of Human Nephron Progenitors.

status: Public on Sep 16 2016

first: Brendan

last: Grubbs

address: 4661 W. Sunset Blvd.

department: Obstetrics and Gynecology

summary: Mature nephrons originate from a small population of uninduced nephrogenic progenitor cells (NPs) within the cap mesenchyme. These cells are characterized by the coexpression of SIX2 and CITED1. Many studies on mouse models as well as on human pluripotent stem cells have advanced our knowledge of NPs, but very little is known about this population in humans, since it is exhausted before birth and strategies for its direct isolation are still limited. Here we report an efficient protocol for direct isolation of human NPs without genetic manipulation or stepwise induction procedures. With the use of RNA-labeling probes, we isolated SIX2+CITED1+ cells from human fetal kidney for the first time. We confirmed their nephrogenic state by gene profiling and evaluated their nephrogenic capabilities in giving rise to mature renal cells. We also evaluated the ability to culture these cells without complete loss of SIX2 and CITED1 expression over time. In addition to defining the gene profile of human NPs, this in vitro system facilitates studies of human renal development and provides a novel tool for renal regeneration and bioengineering purposes

overall_design:
Single cell suspensions from 3 freshly isolated human fetal kidneys ( 17 weeks of gestation) were labelled overnight with RNA probes for SIX2 and CITED1 and sorted to obtain a 1) double positive population and2)  a negative fraction. Long term goal is to investigate the transcription profile that differentiate positive versus negative selections.

***************************************************************
Raw files for human/patient samples were not submitted to GEO due to concerns about submitting personally identifiable sequence data for open access.
***************************************************************

first: Laura

last: Perin

first: Stefano

last: Da Sacco

first: Matthew

last: Thornton


title: mRNA-seq analysis of HCT116 cells following gene overexpression of IDO1 with or without Indole treatment

status: Public on Jul 01 2016

city: Seoul

first: Ji-Hee

last: Shin

address: 1, Gwanak-ro, Gwanak-gu

institute: Seoul National University

summary: To investigate the effect of indole on protection against colon injury and the role of IDO1 expression, we examined the effect of indole on hIDO1-overexpressing and empty vector control HCT116 cells by global gene expression profiling.

overall_design: Examination of mRNA levels from hIDO1-overexpressing and control HCT116 cell lines treated with 1mM indole or DMF for 24 hours using two replicates each.

first: Young-Kwan

last: Lee


title: Prostate cancer stratification using molecular profiles [CamCap ExpressionArray]

status: Public on Jul 30 2015

city: Cambridge

first: Chandra

last: Chilamakuri

address: Robinson Way

country: United Kingdom

institute: Cancer Research UK Cambridge Institute

summary:
Background
Understanding the heterogeneous genotypes and phenotypes of prostate cancer is fundamental to improving the way we treat this disease.  As yet, there are no validated descriptions of prostate cancer subgroups derived from integrated genomics linked with clinical outcome.
Methods
In a study of 482 tumour, benign and germline samples from 259 men with primary prostate cancer, we used integrative analysis of copy number alterations (CNA) and array transcriptomics to identify genomic loci that affect expression levels of mRNA in an expression quantitative trait loci (eQTL) approach, to stratify patients into subgroups that we then associated with future clinical behavior, and compared with either CNA or transcriptomics alone.
Findings
We identified five separate patient subgroups with distinct genomic alterations and expression profiles based on 100 discriminating genes in our separate discovery and validation sets of 125 and 99 men. These subgroups were able to consistently predict biochemical relapse (p=0.0017 and p=0.016 respectively)  and were further validated in a third cohort with long-term follow-up (p=0.027). We show the relative contributions of gene expression and copy number data on phenotype, and demonstrate the improved power gained from integrative analyses. We confirm alterations in six genes previously associated with prostate cancer (MAP3K7, MELK, RCBTB2, ELAC2, TPD52, ZBTB4) in prostate cancer, and also identify 94 genes not previously linked to prostate cancer progression that would not have been detected using either transcript or copy number data alone. We confirm a number of previously published molecular changes associated with high risk disease, including MYC amplification, and NKX3-1, RB1 and PTEN deletions, as well as over-expression of PCA3 and AMACR, and loss of MSMB in tumour tissue. A subset of the 100 genes  outperforms established clinical predictors of poor prognosis (PSA, Gleason score), as well as previously published gene signatures (p=0•0001). We further show how our molecular profiles can be used for the early detection  of aggressive cases in a clinical setting, and inform treatment decisions.
Interpretation
For the first time this study demonstrates the importance of integrated genomic analyses incorporating both benign and tumour tissue data in identifying molecular alterations leading to generation of robust gene sets that are predictive of clinical outcome in independent patient cohorts.

overall_design:
A total of 482 samples from 289 men with prostate cancer from two cohorts were included in this study.  The discovery cohort comprised 125 tumour samples from radical prostatectomy (RP) with 118 matched benign samples, and 85 matched blood samples.  An additional 4 benign samples from men undergoing Holmium laser enucleation of the prostate (HoLEP) and 16 radical prostatectomy samples from men with castrate-resistant prostate cancer, with 13 matched blood samples were also included.  These were assayed on several platforms, including Illumina HT12v4 gene expression arrays, Illumina OMNI2.5M genotyping arrays and Affymetrix SNP6 genotyping arrays.  The validation cohort comprised 103 tumour tissue samples from men with prostate cancer, with 99 matched benign tissue samples and 103 matched blood samples.  This datasheet describes samples in the DISCOVERY COHORT only, with complete, QCd Illumina HT12v4 data for 13 CRPC samples, 113 tumour samples and 73 matched benign samples.
Extensive clinical metadata is available in the associated publication Ross-Adams et al. (2015, Suppl. Table 2)

first: Helen

last: Ross-Adams

first: Alastair

last: Lamb

first: Silvia

last: Halim

first: Mark

last: Dunning


title: Prostate cancer stratification using molecular profiles

type:
Expression profiling by array
Genome variation profiling by SNP array

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

overall_design: Refer to individual Series


title: Distinct regulatory programs for Sox9 in transcriptional regulation of the developing mammalian chondrocyte

status: Public on Jul 01 2015

first: Xinjun

last: He

address: 1425 San Pablo St

department: BROAD CIRM Center

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus


title: The transcription factors SOX9 and SOX5/SOX6 cooperate genome-wide through super-enhancers to drive chondrogenesis

status: Public on Jun 23 2015

city: Cleveland

first: Chia-Feng

last: Liu

state: OH

address: 9500 Euclid Avenue,

department: Cardiovascular & Metabolic Sciences

institute: Cleveland Clinic Lerner Research Institute


title: The transcription factors SOX9 and SOX5/SOX6 cooperate genome-wide through super-enhancers to drive chondrogenesis (ChIP-Seq)

summary: SOX9 is a transcriptional activator required for chondrogenesis, and SOX5 and SOX6 are closely related DNA-binding proteins that critically enhance its function. We used RNA-seq to charatierize a rat chondrosarcoma (RCS) cells as a faithful model for proliferating/early prehypertrophic growth plate chondrocytes and ChIP-seq to gain novel insights into the full spectrum of the target genes and modes of action of this chondrogenic trio.

overall_design: ChIP-seq for SOX9,  SOX6 and histone modifications were carried out using RCS cells

middle: F

first: Veronique

last: Lefebvre


title: Distinct regulatory programs for Sox9 in transcriptional regulation of the developing mammalian chondrocyte [ChIP-seq]

summary: We compared Sox9-association at chondrocyte targets to a broad catalogue of regulatory indicators of chromatin organization and transcriptional activity to determine Sox9’s direct regulatory actions in normal developing chondrocytes. Sox9-associated regions resolve into two distinct regulatory categories. Class I regions closely associate with transcriptional start sites (TSSs). Their targets reflect general regulators of basal cell activities that Sox9 engages indirectly though a likely association with the basal transcriptional complex. In contrast, Class II regions outside of the local TSS domains highlight evolutionarily conserved, active enhancers directing expression of chondrocyte specific target genes, though DNA binding of Sox9-dimers at target sites with sub-optimal binding affinity. The level of associated chondrocyte gene expression correlates with the number of enhancer modules around the target gene and grouping into super-enhancer clusters. Comparison of Sox9 programs between neural crest and mesoderm-derived chondrocytes points to similar modes of chondrocyte specification in distinct chondrocyte lineages. These data provide the first insight into mammalian Sox family actions at the genome scale in the vivo setting. The resulting enhancer sets provide a key resource for further dissection of the regulatory programs of mammalian chondrogenesis.

overall_design: Incorportation of ChIP-seq data of Sox9 and histone modification marks for chromatin status together with micorarray gene expression profiling in neonatal mice chondrocytes to uncover Sox9 regulatory system. Overexpression of Sox9 with a control of EGFP in human fibroblasts to identify the direct targets of Sox9 regulatory system

first: Shinsuke

last: Ohba

first: Hironori

last: Hojo

first: Andrew

last: McMahon


title: Aza treated AML3 cells

status: Public on Jul 01 2014

city: Glasgow

first: Peter

last: Adams

address: Switchback Rd, Bearsden

institute: University of Glasgow, Beatson Institute for Cancer Research

type: Methylation profiling by high throughput sequencing


title: Expression data from prostate cancer and benign prostate glands

city: Aarhus N

first: Martin

middle: Mørck

last: Mortensen

address: Brendstrupgaardsvej 100

department: Dept. of Urology

country: Denmark

institute: Aarhus University Hospital

summary: Prostate cancer is a leading cause of cancer death amongst males. The main clinical dilemma in treating prostate cancer is the high number of indolent cases that confer a significant risk of over diagnosis and over treatment. In this study we have performed a genome expression profiling of tumor tissue specimens from 36 patients with prostate cancer to identify transcripts that delineate aggressive and indolent cancer. We included normal prostate biopsies from 14 patients in our analysis. Unsupervised hierarchical cluster analysis separated the cancer samples into two groups with a significant overrepresentation of tumors from patients with biochemical recurrence in one of the groups (Chi2, p=0.02). The samples were separated by basically three clusters of genes that showed differential expression between the two sample clusters - totaling 371 transcripts. Ingenuity Pathway Analysis revealed that one cluster contained genes associated with invasive properties of the tumor, another genes associated with the cell cycle, and the last cluster genes involved in several biological functions. We successfully validated the transcripts association with recurrence using two publicly available patient datasets totaling 669 patients. Twelve genes were found to be independent predictors of recurrence in multivariate logistical regression analysis.

first: Mørck

middle: M

first: Lars

last: Dyrskjøt


title: Gene expression profiling of the whole mouse brain using transcriptome tomography

status: Public on Sep 21 2012

first: Yuko

last: Okamura-Oho

address: 2-1, Hirosawa

institute: RIKEN

summary: We developed a novel framework to assess comprehensive endogenous gene expression maps in a broad and isotropic 3D-anatomical context using a relatively small number of original data points: transcriptome tomography. Using this method, we produced a dataset of gene expression maps of the whole mouse brain, computationally reconstructed from fraction data.

overall_design: A total of 61 fraction samples obtained with body axes-based slicing preparation conjugated with anatomical image acquisition were analysed. There are two sets of body axes-based preparation series: the S series, composed of 9 fractions/ C of 13 fractions/ H of 6 fractions , and the So series, composed of 10 fractions/ Co of 16 fractions/ Ho of 7 fractions.

first: Hideo

last: Yokota


title: DNA Methylation by Reduced Representation Bisulfite Seq from ENCODE/HudsonAlpha

status: Public on Mar 01 2011

city: Stanford

first: ENCODE

last: DCC

address: 300 Pasteur Dr

institute: ENCODE DCC

summary:
This data was generated by ENCODE. If you have questions about the data, contact the submitting laboratory directly (Florencia Pauli mailto:fpauli@hudsonalpha.org). If you have questions about the Genome Browser track associated with this data, contact ENCODE (mailto:genome@soe.ucsc.edu).

This track is produced as part of the ENCODE project. The track reports the percentage of DNA molecules that exhibit cytosine methylation at specific CpG dinucleotides. In general, DNA methylation within a gene's promoter is associated with gene silencing, and DNA methylation within the exons and introns of a gene is associated with gene expression. Proper regulation of DNA methylation is essential during development and aberrant DNA methylation is a hallmark of cancer. DNA methylation status is assayed at more than 500,000 CpG dinucleotides in the genome using Reduced Representation Bisulfite Sequencing (RRBS). Genomic DNA is digested with the methyl-insensitive restriction enzyme MspI, small genomic DNA fragments are purified by gel electrophoresis, and then used to construct an Illumina sequencing library. The library fragments are treated with sodium bisulfite and amplified by PCR to convert every unmethylated cytosine to a thymidine while leaving methylated cytosines intact. The sequenced fragments are aligned to a customized reference genome sequence and for each assayed CpG we report the number of sequencing reads covering that CpG and the percentage of those reads that are methylated.
For data usage terms and conditions, please refer to http://www.genome.gov/27528022  and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf

overall_design:
DNA methylation at CpG sites was assayed with a modified version of Reduced Representation Bisulfite Sequencing (RRBS; Meissner et al., 2008). RRBS was performed on cell lines grown by many ENCODE production groups. The production group that grew the cells and isolated genomic DNA is indicated in the "obtainedBy" field of the metadata. When a cell type was provided by more than one lab, the data for the cells from only one lab are displayed in the table above. However, the data for every cell type from every lab is available from the Downloads page. RRBS was carried out by the Myers production group at the HudsonAlpha Institute for Biotechnology.
Isolation of genomic DNA
Genomic DNA is isolated from biological replicates of each cell line using the QIAGEN DNeasy Blood & Tissue Kit according to the instructions provided by the manufacturer. DNA concentrations for each genomic DNA preparation are determined using fluorescent DNA binding dye and a fluorometer (Invitrogen Quant-iT dsDNA High Sensitivity Kit and Qubit Fluorometer). Typically, 1 µg of DNA is used to make an RRBS library; however, we have also had success in making libraries with 200 ng genomic DNA from rare or precious samples.
RRBS library construction and sequencing
RRBS library construction starts with MspI digestion of genomic DNA , which cuts at every CCGG regardless of methylation status. Klenow exo- DNA Polymerase is then used to fill in the recessed end of the genomic DNA and add an adenosine as a 3prime overhang. Next, a methylated version of the Illumina paired-end adapters is ligated onto the DNA. Adapter ligated genomic DNA fragments between 105 and 185 basepairs are selected using agarose gel electrophoresis and Qiagen Qiaquick Gel Extraction Kit. The selected adapter-ligated fragments are treated with sodium bisulfite using the Zymo Research EZ DNA Methylation Gold Kit, which converts unmethylated cytosines to uracils and leaves methylated cytosines unchanged. Bisulfite treated DNA is amplified in a final PCR reaction which has been optimized to uniformly amplify diverse fragment sizes and sequence contexts in the same reaction. During this final PCR reaction uracils are copied as thymines resulting in a thymine in the PCR products wherever an unmethylated cytosine existed in the genomic DNA. The sample is now ready for sequencing on the Illumina sequencing platform. These libraries were sequenced with an Illumina Genome Analyzer IIx according to the manufacturer's recommendations.
Data analysis
To analyze the sequence data, a reference genome is created that contains only the 36 base pairs adjacent to every MspI site and every C in those sequences is changed to T. A converted sequence read file is then created by changing each C in the original sequence reads to a T. The converted sequence reads are aligned to the converted reference genome, and only reads that map uniquely to the reference genome are kept. Once reads are aligned the percent methylation is calculated for each CpG using the original sequence reads. The percent methylation and number of reads is reported for each CpG.

first: Katherine

last: Varley

first: Jason

last: Gertz

first: Richard

last: Myers


title: Expression data from untreated and Aza treated AML3 cells

city: La Jolla

middle: D.

address: 10901 North Torrey Pines Road

department: Cancer Genome and Epigenetics Program

institute: Sanford Burnham Prebys Medical Discovery Institute

summary: AML3 cells were treated with Azacytidine and compared against untreated cells

overall_design: We used RNA-Seq to detail the global programme of gene expression in human untreated and Azacytidine treated AML3 cells

first: Kirstin

last: Lund

first: Tony

last: McBryan

first: John

middle: J

last: Cole


title: microRNA profiling of mesenchymal stem cells from adipose tissue of differentially aged mice

status: Public on Nov 30 2010

city: Verona

first: Mirco

last: Galiè

address: via Le Grazie, 8

department: Neuroscience, Biomedicine and Movement Sciences

country: Italy

institute: University of Verona

summary: The data presented here is part of a study aimed to investigate whether the gene expression profile of Polycomb, Trithorax and interacting molecules might be related to different states of differentiative potential.

overall_design: microRNA profiling (Exiqon miRCURY LNA array Version 9.2) has been performed on mesenchymal stem cells isolated from the inguinal fat pad of mice of 1 (n=2), 3(n=2), 6(n=2), 12(n=2) and 24(n=1) months of age.

first: Daniele

last: Peroni

first: Ilaria

last: Scambi


title: The transcriptional landscape of pericytes in acute ischemic stroke

status: Public on Jun 29 2023

city: Lund

first: Robert

last: Carlsson

address: Sölvegatan 17

department: IKVL

country: Sweden

institute: Lund University

summary: The current treatment options for ischemic stroke aim to achieve reperfusion but are time critical. Novel therapeutic approaches that can be given beyond the limited time window of 3 - 4.5 hours are still an unmet need to be addressed to improve stroke outcome. The lack of oxygen and glucose in the area of ischemic injury initiates a pathological cascade leading to blood-brain barrier (BBB) breakdown, inflammation and neuronal cell death, a process that may be intercepted to limit stroke progression. Pericytes located at the blood/brain interface are one of the first responders to hypoxia in stroke and therefore a potential target cell for early stroke interventions. Using single-cell RNA sequencing in a mouse model of permanent middle cerebral artery occlusion, we investigated the temporal differences in transcriptomic signatures in pericytes at 1, 12, and 24 hours after stroke compared to the contralateral hemisphere. Our results reveal a stroke-specific subcluster of pericytes that is present at 12 and 24 hours and characterized by the upregulation of genes mainly related to cytokine signalling and immune response.   This study identifies temporal transcriptional changes in the acute phase of ischemic stroke that reflect the early response of pericytes to the ischemic insult and its secondary consequences and may constitute potential future therapeutic targets.

overall_design: Live non-neuronal single cells from ipsilateral or contralateral cortex of heterozygous RGS5::GFP mice were sequenced after 1h, 12h or 24h permanent middle cerebral artery occlusion.

first: Andreas

last: Enström

first: Carolina

last: Buizza

first: Gesine

last: Paul-Visse


title: Comparative transcriptome analysis between six adipose depots in buffaloes

status: Public on May 17 2023

city: Nanning

first: Huang

last: JiePing

address: Xixiangtang District

institute: Guangxi University

summary: To characterize the transcriptome differences between different adipose depots, a total of 36 adipose samples were used for high-throughput sequencing. At last, about 23,000 transcripts were identified.

overall_design: A total of 36 adipose samples were used for RNA sequencing, including 3 subcutaneous adipose tissue (SAT) depots (back subcutaneous adipose tissue, BSAT; sternum subcutaneous adipose tissue, SSAT; inguinal adipose tissue, IAT) and 3 visceral adipose tissue (VAT) depots (omental adipose tissue, OAT; pericardial adipose tissue, PCAT; perirenal adipose tissue, PRAT) in 6 buffaloes.

first: Jieping

last: Huang


title: Coordinated chemokine expression defines macrophage subsets across tissues [scRNA-seq: mLu]

status: Public on Mar 03 2023

city: Lebanon

first: Claudia

last: Jakubzick

state: NH

address: 1 Medical Center Drive, Rm 626 W Borwell, PO#1250960

department: Microbiology and Immunology

institute: Dartmouth College

summary: Lung-resident macrophages, which include alveolar macrophages and interstitial macrophages (IMs), exhibit a high degree of diversity, generally attributed to different activation states, and often complicated by the influx of monocytes into the pool of tissue-resident macrophages. To gain a deeper insight into the functional diversity of IMs, here we perform comprehensive transcriptional profiling of resident IMs and reveal ten distinct chemokine-expressing IM subsets at steady state and during inflammation. Similar IM subsets that exhibited coordinated chemokine signatures and differentially expressed genes were observed across various tissues and species, indicating conserved specialized functional roles. Other macrophage types shared specific IM chemokine profiles, while also presenting their own unique chemokine signatures. Depletion of CD206hi IMs in Pf4creR26EYFP+DTR and Pf4creR26EYFPCx3cr1DTR mice led to diminished inflammatory cell recruitment, reduced tertiary lymphoid structure formation and fewer germinal center B cells in models of allergen- and infection-driven inflammation. These observations highlight the specialized roles of IMs, defined by their coordinated chemokine production, in regulating immune cell influx and organizing tertiary lymphoid tissue architecture.

overall_design: Three groups of C57BL/6 mice (n=2) were treated for cell collection. LPS was intranasally administrated to mice with 10 ug in 50 ul sterile PBS 24 hours before harvest. a-Gr1 Ab was intraperitoneally administrated to mice with 300 ug in 300 ul also 24 hours before harvest. Mice in group 1 are naïve mice without any treatment, where the collected cells are expected to contain only steady-state IMs; mice in group 2 are treated with LPS i.n. to introduce acute inflammatory lung injury, where the collected cells are expected to contain both stimulated IMs and recruited monocytes; mice in group 3 are treated with LPS i.n. and a-Gr1 Ab to introduce injury and block the recruitment of blood monocytes, where the collected cells are expected to contain only stimulated IMs. To differentiate intravascular and extravascular leukocytes, mice were injected intravenously with APC-Cy7-conjugated anti-CD45 antibody 5 minutes before organ harvest. The mice were euthanized using CO2 inhalation.

first: Xin

last: Li

first: Arlind

middle: B

last: Mara

first: Shawn

last: Musial

first: Fred

middle: W

last: Kolling

first: Sophie

middle: T

last: Gibbings

first: Nikita

last: Gerebtsov


title: Transciptome profile of TrmB and TbsP, Genome-wide binding of TbsP (HVO_2861) in Haloferax volcanii

status: Public on Dec 01 2023

first: Amy

middle: K

last: Schmid

address: 124 Science Dr

institute: Duke University


title: Time-dependent specific molecular signatures of inflammation and remodelling are associated with Trimethylamine-N-oxide (TMAO)-induced endothelial cell dysfunction

status: Public on Nov 23 2023

city: Singapore

first: Meyammai

last: Shanmugham

address: 8 Somapah Road

department: Science, Mathematics, and Technology

country: Singapore

institute: Singapore University of Technology and Design

summary: Cardiovascular diseases (CVDs) are leading causes of death worldwide. Endothelial dysfunction is a critical initiating factor contributing to CVDs, which progression involves the gut microbiome-derived metabolite Trimethylamine N-oxide (TMAO). Here, we aim to clarify the time-dependent pathways by which TMAO mediates endothelial dysfunction.

overall_design: We performed transcriptomics and metabolomics analyses on human microvascular endothelial cells (HMEC-1) treated with TMAO. Differentially expressed genes (DEG) and gene set enrichment analysis (GSEA) followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses allowed the identification of specific molecular pathways. Cell viability and reactive oxygen species (ROS) generation were also evaluated.

first: Arun

last: Devasia

first: Yu

middle: L

last: Chin

first: Kang

last: Cheong

first: Eng

middle: S

last: Ong

last: Bellanger

first: Adaikalavan

last: Ramasamy

first: Chen

last: Leo


title: Macrophage Mannose receptor (MRC1) mediates uptake of dextran in murine bone-marrow derived macrophages via a receptor-mediated endocytic process

status: Public on Oct 01 2023

city: Brookings

first: Natalie

last: Thiex

state: SD

address: 1066 Campanile Ave, Box 2022A ookings

department: Biology and Microbiology

institute: South Dakota State University

summary: CRISPR/Cas9 whole genome screens identify regulators of dextran utpake

sample_organism:
Mus musculus
synthetic construct

platform_organism:
Mus musculus
synthetic construct

first: Jared

last: Wollman

first: Lu

last: Huang


title: Genetic activation of glycolysis in osteoblasts preserves bone mass in type I diabetes [scRNA-seq]

status: Public on Jun 20 2023

city: PHILADELPHIA

first: XING`

last: JI

address: 3401 Civic Center Blvd

institute: Children's hospital of Philadelphia

summary: Type I diabetes (T1D) impairs bone accrual in patients, but the mechanism is unclear.  Here in a murine monogenic model for T1D, we demonstrate that diabetes suppresses bone formation resulting in a rapid loss of both cortical and trabecular bone.  Single-cell RNA sequencing uncovers metabolic dysregulation in bone marrow osteogenic cells of the diabetic mice.  In vivo stable isotope tracing reveals impaired glycolysis in diabetic bone that is highly responsive to insulin stimulation.  Remarkably, deletion of the insulin receptor reduces cortical but not trabecular bone.  Increasing glucose uptake by overexpressing Glut1 in osteoblasts exacerbates bone defects in T1D mice.  Conversely, activation of glycolysis by Pfkfb3 overexpression preserves both trabecular and cortical bone mass in the face of diabetes.  The study identifies defective glucose metabolism in osteoblasts as a pathogenic mechanism for osteopenia in T1D, and furthermore implicates boosting osteoblast glycolysis as a potential anabolic therapy.

overall_design: single-cell RNA-sequencing profiling of endosteal cells from WT and Akita at 8 weeks and 20weeks, n=1 for each genotype

first: Xing

last: Ji

first: Fanxin

last: Long


title: Chemifortification of leaves through enhanced metabolic flux to tocopherol biosynthesis and plastoglobule proliferation.

status: Public on Feb 19 2026

city: Valencia

first: Javier

last: Forment

address: Ingeniero Fausto Elio, s/n

country: Spain

institute: Instituto de Biología Molecular y Celular de Plantas, IBMCP (Universitat Politècnica de València-CSIC)

summary: Plant biofortification with phytonutrients typically relies on metabolic engineering strategies known as “push” (enhancing biosynthetic flux), “block” (inhibiting competing pathways), and “pull” (promoting metabolite storage). Here, we describe a novel chemifortification approach independent of genetic manipulation. A chemical screening identified X57, a synthetic compound that simultaneously activates all three mechanisms to enhance leaf tocopherol content. Besides their dietary value as vitamin E, tocopherols protect plants against oxidative stress and they are highly appreciated antioxidants in food and cosmetic formulations. X57 exerts a primary “push” effect by inducing tocopherol biosynthesis, in part by reactivating a direct pathway that reduces geranylgeranyl diphosphate (GGPP) to phytyl diphosphate, bypassing the need for chlorophyll-derived phytol. Accordingly, X57 promotes tocopherol accumulation in etiolated seedlings and restores tocopherol synthesis in mutants deficient in phytol phosphorylation. The “block” effect is mediated by downregulation of GGPP consumption for carotenoid synthesis. X57 also induces a “pull” effect via proliferation of plastoglobules (PG), plastidial lipoprotein bodies that synthesize and store tocopherols. X57-induced PG proliferation is driven by increased tocopherol levels and upregulation of genes for PG structural proteins such as fibrillins. X57 thus provides a powerful chemical tool for non-genetic vitamin E biofortification but also to better understand the coordination of plastidial isoprenoid metabolism and plastid differentiation.

overall_design: RNA-seq profiling of 5-day-old Arabidopsis thaliana seedlings treated with the chemical compound X57 or with mock conditions (0.05% DMSO) for 5 hours.

first: Pablo

last: Perez-Colao

first: Gaetan

last: Glauser

first: Jorge

last: Lozano-Juste

first: Manuel

last: Rodriguez-Concepcion


title: Characterization of cellular miRNA transcriptome during KSHV lytic reactivation

status: Public on Feb 24 2026

city: Boston

first: Soo Mi

last: Lee

address: 3 BLACKFAN CIRCLE, CLS 417

department: Pathology

institute: BIDMC/Harvard Medical School

summary:
Purpose: To characterize genome-wide microRNA (miRNA) expression profiles in the context of Kaposi's sarcoma-associated herpesvirus (KSHV) lytic reactivation.

Methods: We utilized a well-established model of KSHV reactivation, the doxycycline (Dox)-inducible KSHV producer cell line iSLK.219, which contains a latent KSHV genome and a Dox-inducible KSHV lytic switch protein RTA (replication and transcription activator) to mediate efficient reactivation upon Dox treatment. We performed small-RNA sequencing of RNA isolated from latent KSHV-infected iSLK.219 cells at 0 h or lytic iSLK.219 cells at 72 h post Dox-induced KSHV lytic reactivation using Illumina HiSeq 2500. To rule out the possibility that Dox itself can affect miRNA expression, we also performed small-RNA sequencing of RNA isolated from KSHV-negative iSLK cells, which lacks the KSHV genome but harbors the Dox-inducible RTA transgene, without Dox treatment at 0 h or at 72 h post Dox treatment. The mappable reads were aligned to the human genome and miRBase using Bowtie.

Results: Global cellular miRNA transcriptome analysis has identified changes in the host miRNA expression landscape during the switch from latent to lytic KSHV replication. The top down-regulated miRNAs included miR-31-5p, miR-29a-3p, miR-181a-3p, miR-194-5p, and miR-449c-5p and the top up-regulated miRNAs included miR-139-5p, miR-7-5p, miR-210-3p and miR-3065-5p. We confirmed that Dox treatment in KSHV-negative iSLK cells did not significantly down-regulate or up-regulate these cellular miRNAs, indicating that Dox itself or RTA transgene expression alone does not affect the levels of these miRNAs. In addition, 8 KSHV-encoded miRNAs, including pre-miR-K12-12, were significantly up-regulated upon lytic reactivation in iSLK.219 cells. Notably, the top four up-regulated host miRNAs have been implicated in inflammatory signaling pathways involved in a productive or lytic cycle of infection, suggesting that KSHV exploits these immunomodulatory miRNAs to facilitate lytic reactivation. On the contrary, four out of the top five down-regulated host miRNAs, miR-29a-3p, miR-181a-3p, miR-194-5p, and 449c-5p have been implicated in restricting the infection and replication of RNA and DNA viruses. Taken together with our small-RNA sequencing analysis, these findings suggest that KSHV lytic reactivation impacts the cellular miRNA expression landscape as a strategy to evade or subvert host antiviral responses and ensure efficient lytic replication and persistence.

Conclusions: Our study represents the first detailed analysis of genome-wide miRNA transcriptomes during KSHV lytic reactivation, with biological replicates, generated by miRNA-seq technology. Our study provides crucial insights into the impact of lytic KSHV infection on the host and viral miRNA expression landscapes. Moreover, our results identify a previously unappreciated role for miR-31-5p in regulating KSHV lytic reactivation by modulating KHDRBS3 expression.

first: SooMi

first: Frank

last: Slack


title: DDX53 binds a wide range of RNA molecules in human TCam-2 cells (eCLIP data)

status: Public on Feb 12 2026

city: Poznan

first: IHG PAS

last: Bioinfo Team

state: Greater Poland

address: Strzeszynska 32

department: Bioinformatics Team

country: Poland

institute: Institute of Human Genetics, Polish Academy of Sciences

summary: DDX53 (DEAD-box helicase 53, known also as CAGE) is an intronless gene on the X chromosome, which expression shows strong testis and brain specificity. Additionally, it belongs to the group of cancer-testis (CT) antigens, with most studies to date focusing on its role in cancer. Previous reports of rare variants within the DDX53 in infertile men have provided a rationale for our study of DDX53 in the context of human spermatogenesis. By using the human seminoma cell line (TCam-2) as an in vitro male germline model, we aimed to investigate the function and molecular targets of DDX53 protein. Our eCLIP and RNA-seq data show that DDX53 protein binds a wide repertoire of RNA targets, drives transcriptome changes in human cells, and is involved in alternative splicing of RNA transcripts. Further, we examined the localization of DDX53 using confocal microscopy, revealing that it is mainly located in the cytoplasm, but also in the nucleus of TCam-2 cells. Our data indicate that DDX53 protein acts as a regulator of RNA metabolism in human cells. Collectively, we show that DDX53 participates in transcriptome regulation (including splicing) in male germ cells and exhibits transcriptome-wide RNA interactions, but its wider biological role remains to be clarified.

overall_design: Two biological replicates of TCam-2 cells expressing the DDX53-FLAG were used in eCLIP-seq performed by Eclipse BioInnovations (USA). Cells were crosslinked, then lysed, RNase I treated, and protein-RNA complexes were immunoprecipitated with anti-FLAG antibody coupled to magnetic beads. The eCLIP experiment was performed by Eclipse BioInnovations’ standard RBP-eCLIP pipeline.

first: Natalia

last: Rozwadowska

first: Agata

last: Barszcz

first: Erik

last: Dassi


title: Maternal antibodies orchestrate the establishment of salivary and oral mucosal immunity_Gingiva

status: Public on Feb 23 2026

city: Jerusalem

first: Inbar

last: Plaschkes

address: The Hebrew University of Jerusalem - Ein Kerem

department: The Faculty of Medicine - Ein Kerem

country: Israel

institute: HUJI

summary: The establishment of mucosal homeostasis after birth involves mutual development of the microbiota and the immune system, with each mucosal barrier has specific mechanisms. Here, we show that in utero-delivered maternal IgG antibodies are translocated to the salivary glands and secreted to the neonatal saliva. As a result, the microbial burden of the neonate oral cavity and salivary glands is reduced. In the absence of maternal antibodies, oral dendritic cells migrate in higher frequencies to the salivary glands resulting in elevated activation of T and B cells, while dampening T regulatory cells. The IgG/IgA balance in the adult saliva was also dysregulated. The absence of maternal antibodies further regulates the adult gingival immunity, a key oral barrier, increasing alveolar bone loss during experimental periodontitis. This work reveals the importance of the salivary-oral axis during neonatal life via maternal antibodies, orchestrating local mucosal immunity and protecting against pathological damage in adulthood.

overall_design: B cell-deficient (JhT-/- ) females were crossed with wild-type (WT) males to generate offspring with intact B cells that were not exposed to mIg.

first: Reem

last: Naamneh

first: Avi-Hai

last: Hovav

first: Yasmin

last: Netanely

first: Shahd

last: Yacoub

last: Jaber


title: DDX53 drives transcriptome changes in human TCam-2 cells (RNA-seq data)

overall_design: The RNA-seq experiment was done in duplicate and performed using TCam-2 cells transduced with DDX53-FLAG, GFP-FLAG and non-transduced WT. Cells transduced with GFP-FLAG and non-transduced WT TCam-2 cells were used as negative controls in order to perform analysis of differentially expressed and differentially spliced genes upon DDX53 overexpression. RNA-seq data from non-transduced WT TCam-2 cells and TCam-2 transduced with GFP-FLAG are deposited in the GEO database under accession code GSE294696.

first: Katarzyna

last: Tutak

first: Joanna

last: Zyprych-Walczak

first: Erkut

last: Ilaslan


title: E96A TMZ Treatment Study

status: Public on Feb 04 2026

city: Indianapolis

first: Kelley

last: Mark

state: Indiana

institute: Herman B Wells Center for Pediatric Research

summary: Temozolomide (TMZ) induces DNA alkylation lesions repaired primarily through base excision repair. To characterize transcriptional responses to TMZ in the context of impaired APE1 endonuclease activity, RNA-seq was performed on Pa03C Cas9 and E96A mutant cell lines following treatment. Cells were treated with TMZ for 4 hours or 8 hours, along with untreated controls. This dataset captures genotype-specific and time-dependent transcriptional responses to alkylation stress in PDAC cells.

overall_design: Pa03C PDAC cell lines carrying either a Cas9 control allele or a homozygous APE1 E96A endonuclease-deficient mutation were treated with temozolomide (TMZ) or left untreated. For each genotype, cells were collected at baseline (untreated), 4 hours after TMZ treatment, and 8 hours after TMZ treatment. Total RNA was isolated each individual sample. This design enables comparison of genotype-specific and time-dependent transcriptional responses to TMZ-induced DNA damage

first: Eyram

last: Kpenu

first: Mark

last: Kelley


title: Unravelling the role of ASN1 gene in the model legume Lotus japonicus

status: Public on Feb 05 2026

city: Sevilla

first: MARCO

last: BETTI

state: Sevilla

address: C. Prof. García González 1

department: Bioquímica Vegetal y Biología Molecular

institute: Universidad de Sevilla

summary: Asparagine constitutes the major form of nitrogen translocated within Lotus japonicus plants. Previous work had indicated that the different genes encoding for asparagine synthetase (ASN genes) show differential patterns of expression in different organs from plants grown under either symbiotic (S) or non-symbiotic (NS) conditions.  In this work we use knock out mutants deficient in LjASN1 gene, which is the most highly expressed ASN gene in NS conditions, but much less expressed under S conditions. The analysis of two different lines of LORE 1 Ljasn1 homozygous mutant plants grown in the presence complete nutrient medium (NS) or with Mesorhizobium loti (S) was comparatively examined with respect to the WT. The results obtained indicate that a much higher biomass was produced in Ljasn1 mutants grown under NS conditions compared to the WT, while little difference was observed in the mutant plants compared to the WT under S conditions. The results point out a relationship between the deficiency of the ASN1 gene and growth of L. japonicus plants mainly under NS conditions. Further metabolomic analysis revealed that Ljasn1 mutant plants are quite distinct to WT plants when grown under NS conditions, but not under S conditions, in accordance with previous results. Interestingly, asparagine level was considerably reduced in Ljasn1 mutant plants compared to the WT when plants were grown under NS but not under S conditions, thus confirming the crucial relevance of ASN1 in the asparagine levels found in the plants under NS conditions. The results from whole metabolomics analysis, together with other obtained by RNA seq analysis, indicate that ASN1 deficiency produce important changes in the C/N balance and metabolite allocation of  L. japonicus plants resulting in a higher biomass content.

overall_design: A comparative RNAseq analysis of WT and of Ljasn1_2 mutant, KO for the LjAsn1 gene encoding for one isoform of asparagine synthetase was carried out.Shoots, roots or nodulated roots were harvested from plants grown either with ammonium nitrate or under symbiotic conditions. WT and mutant tissues were harvested after 4 hours of the beginning of the light period after 40 days of growth under symbiotic or non-symbiotic (provided with ammonium nitrate) conditions.

first: Sara

last: Rosa-Téllez

first: Marco

last: Betti

first: Alisdair

last: Fernie

first: Antonio

last: Márquez

first: Margarita

last: García-Calderón


title: NanoString expression profiling of histologically normal breast lobules from NHBW and NHWW donors (BC360)

status: Public on Feb 02 2026

city: Jacksonville

first: Derek

middle: Charles

last: Radisky

state: Florida

address: 4500 San Pablo Road

department: Cancer Biology

institute: Mayo Clinic

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

overall_design: Refer to individual Series


title: Function of CHG methylation dynamics in rice male gametogenesis

status: Public on Jun 24 2023

city: wuhan

first: zhu

last: bo

state: beijing

address: shi zi shan street

department: National Key Laboratory of Crop Genetic Improvement

institute: Huazhong Agricultural University

summary: In this work, we analyzed DNA methylation in rice male meiocyte, microspore and sperm and studied the function of a set of chromatin regulators during the process. The results indicate that that DNA methylation remodeling started after meiosis of the male meiocytes and that non-CG, particularly CHG, methylation is dynamically remodeling during rice male gametogenesis. The work reveals distinct function of DNA methyltransfesaes and histone demethylase in the remodeling of CHG methylation and suggests that the CHG methylation remodeling has functional significance for male gametogenesis and fertilization.

overall_design: Germ cells were obtained by micromanipulation. DNA methylation and transcriptome libraries were constructed by scBS-seq and scRNA-seq techniques. In addition, a seedling DNA methylation library was constructed by directly extracting whole genome DNA.

first: Xue

last: Li

first: Bo

last: Zhu


title: Transcriptome profiling between unfavorable and favorable Wilms Tumors and against human fetal kidney

status: Public on Jul 01 2023

city: West Hollywood

first: AGCT

last: Core

address: 8687 Melrose Ave, PDC B230

department: BMS

institute: Cedars Sinai Medical Center

summary:
Purpose: The 10x Genomics Visium platform allows us to define the spatial topography of gene expression and provides detailed molecular maps that overcome limitations associated with sn/scRNA-seq and microscopy-based spatial transcriptomics methods. The goals of this study are to compare and identify unique transcriptome profiling (RNA-seq) signature between unfavorable and favorable Wilms Tumors and against human fetal kidney.
Methods: Human fetal kidney and Wilms tumor spatial topography of gene expression were generated using the 10X Visium platform
Results: Using an optimized data analysis workflow, we mapped the reads to the hg38 genome build and grouped the spots into 9 clusters based on gene expression profiles.
Conclusion: Our study represents the first implement of Visium technology in human fetal kidney and Wilms Tumor tissue, providing a number of important functional insights about the spatial and molecular definitions of cell populations across human fetal kidney and different subtypes of Wilms Tumor through analyzing gene expression within the intact spatial organization of the human samples.

overall_design: Three total samples, one healthy fetal kidney and two Wilms tumor samples

first: Laura

last: Perin


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

status: Public on Apr 17 2023

city: Santander

first: Lucio

last: Di Filippo

address: PCTCAN - Cl. Albert Einstein, 22

institute: IBBTEC

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

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

first: James

last: Daly

first: Chris

last: Danson

first: Davide

last: Cacchiarelli

first: Andrea

last: Ballabio

first: Peter

last: Cullen