title: ChIA-PET from GM19238 (ENCSR527RXH)

summary:
RAD21 ChIA-PET in GM19238

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIA-PET from GM19239 (ENCSR332ZHA)

status: Public on Mar 03 2019

city: Stanford

first: ENCODE

last: DCC

state: CA

address: 300 Pasteur Dr

country: USA

institute: ENCODE DCC

type: Genome binding/occupancy profiling by high throughput sequencing

summary:
H3K4me2 ChIA-PET in GM19239

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIA-PET from K1 (ENCSR314HAC)

summary:
RAD21 ChIA-PET in human K1 cells

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIA-PET from GM19240 (ENCSR312TUD)

summary:
RAD21 ChIA-PET in GM19240

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIA-PET from GM12891 (ENCSR299VMZ)

summary:
RAD21 ChIA-PET in GM12891

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIA-PET from MCF-7 (ENCSR255XYX)

summary:
RAD21 ChIA-PET in human MCF-7 cells

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIA-PET from neural progenitor cell (ENCSR247RGI)

summary:
RAD21 ChIA-PET in human neural progenitor cells

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIA-PET from GM19240 (ENCSR130SRF)

summary:
H3K4me2 ChIA-PET in GM19240

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIA-PET from SU-DHL-2 (ENCSR128RPG)

summary:
RAD21 ChIA-PET in human SU-DHL-2 cells

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIA-PET from LNCAP (ENCSR113OIR)

summary:
RAD21 ChIA-PET in human LNCAP cells

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIA-PET from GM12892 (ENCSR033GUP)

summary:
RAD21 ChIA-PET in GM12892

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIA-PET from GM19238 (ENCSR029IXY)

summary:
H3K27ac ChIA-PET in GM19238

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIA-PET from GM19239 (ENCSR018VOS)

summary:
H3K4me1 ChIA-PET in GM19239

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIA-PET from GM19240 (ENCSR025JPD)

summary:
H3K4me3 ChIA-PET in GM19240

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIA-PET from K562 (ENCSR000FDG)

summary:
H3K27ac ChIA-PET in K562

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIA-PET from K562 (ENCSR000FDF)

summary:
H3K4me3 ChIA-PET in K562

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIA-PET from K562 (ENCSR000FDE)

summary:
H3K4me2 ChIA-PET in K562

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIA-PET from K562 (ENCSR000FDC)

summary:
POLR2A ChIA-PET in K562

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIA-PET from K562 (ENCSR000FDB)

summary:
RAD21 ChIA-PET in K562

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: ChIA-PET from K562 (ENCSR000FDD)

summary:
H3K4me1 ChIA-PET in K562

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: The chromatin architecture at glucocorticoid-induced genes PER1 and IRAK3

city: Nijmegen

first: Cheng

last: Wang

address: Geert Grooteplein 28

department: Molecular biology

country: Netherlands

institute: Radboud Institute for Molecular Life Sciences

summary: Glucocorticoids (GCs) are essential steroid hormones that regulate the immune system. GCs have been widely used to treat various inflammation disorders and auto-immune diseases, due to their potent immune repression properties.

overall_design: Monocytes from healthy donors were cultured in the presence of 1 uM triamcinolone acetonide (TA). Cells were then collected for 4C-seq.

first: Logie

last: Colin


title: Transcriptome landscape of HeLa response upon triamcinolone acetonide

type: Expression profiling by high throughput sequencing

overall_design: HeLa cells were cultured with DMEM plus 10% charcoal-stripped FBS. HeLa cells were treated in the presence of 100 nM triamcinolone acetonide (TA) for 4 hours. Cells were then collected for RNA-seq.


title: RNA-Sequencing of human dermal lymphatic endothelial cells (HDLEC) treated with siRNA targeting YAP/TAZ and YAP5SA

city: Daejon

first: Hyunsoo

last: Cho

address: Daehak-ro

country: South Korea

institute: KAIST

summary: We analyzed genome-wide transcriptional changes induced by siYAP/TAZ and YAP5SA, using RNA-seq analysis of HDLECs in order to highlight the importance of Hippo/YAP signaling pathway in lymphatic development and maintenance. Here, we report that YAP/TAZ activity is essential for the appropriate lymphatic development and maintenance.

overall_design: Examination of siRNAs treated to HDLEC to analyze the effect of YAP and TAZ knockdown. Three different siRNAs were evaluated for knockdown efficiency, and the most efficient one was used for quadraple samples included in this series.  Effect of YAP5SA overexpression was confirmed with YAP/TAZ target gene enrichment.

first: Gou

middle: Y

last: Koh


title: Transcriptome landscape of human primary monocytes response upon different ligand glucocorticoids

overall_design: Monocytes from healthy donors were cultured in the presence of 100 nM triamcinolone acetonide (TA), 100 nM Dexamethasone (Dex) or 100 nM Prednisolone (Pred) for 4 hours. Cells were then collected for RNA-seq.


title: Upregulation of TFH profile in absence of Ets1 expression

city: Pohang

first: Chan Johng

last: Kim

state: Gyeongbuk

address: Nam-Gu, Cheongam-Ro 77, POSTECH Biotech Center

institute: Institute for Basic Science / Pohang University of Science and Technology

summary: To characterize the effect of loss of Ets1 in Non-TFH and TFH cells, we performed gene expression RNAseq analysis for T follicular helper (TFH) and Non-T follicular helper (Non-TFH) cells in WT (Ets1 fl/fl) and Ets1 KO (CD4-cre Ets1 fl/fl) mice.

overall_design: Total RNA was extracted from splenic CD4+CXCR5+PD-1+ TFH and CD4+CXCR5-PD-1- Non-TFH cells in Ets1 fl/fl and CD4-cre Ets1 fl/fl mice and analyzed by RNA-seq.

first: Chan

middle: J

first: Ambarnil

last: Ghosh

first: Gi-Cheon

first: Dipayan

last: Rudra

first: Sin-Hyeog

last: Im


title: Ets1 suppresses the expression of key TFH genes to block TFH differentiation

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

overall_design: Refer to individual Series


title: The epigenome and glucocorticoid receptor binding of human monocytes and monocyte-derived macrophages with or without glucocorticoid treatment

summary: Glucocorticoids (GCs) are essential steroid hormones that regulate the immune system. GCs have been widely used to treat various inflammation disorders and auto-immune diseases due to their potent immune suppressive properties.

overall_design: Monocytes from healthy donors and the respective monocyte-derived macrophages were cultured in the presence of triamcinolone acetonide (TA) for 4 hours. Cells were then collected for  ChIP-seq.


title: Transcriptomes of human monocytes and monocyte-derived macrophages with or without glucocorticoid treatment

overall_design: Monocytes from healthy donors and the respective monocyte-derived macrophages were cultured in the presence of triamcinolone acetonide (TA) for 4 hours. Cells were then collected for  RNA-seq.


title: ChIA-PET from ARPE-19 (ENCSR110JOO)

summary:
RAD21 ChIA-PET in human ARPE-19 cells

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: The nuclei of somatic cells fused to mouse embryonic stem cells express pluripotency markers similar to early reprogramming events

status: Public on Mar 02 2019

city: Blacksburg

first: M. Cristina

last: Villafranca

state: VA

address: 205 Duckpond Drive

institute: Virginia Polytechnic Institute and State University

summary: The mechanisms that direct nuclear reprogramming to a pluripotent state are still not fully understood. For species in which the derivation of true induced pluripotent stem (iPS) cells has not yet been completely successful, insights into the particular mechanisms that govern pluripotency can help in determining which are the appropriate conditions to induce stable reprogramming in somatic cells. Cell fusion of a somatic cell to a pluripotent cell is known to induce expression of pluripotency markers in the somatic nucleus. We hypothesized that fusion of bovine fetal fibroblasts (bFFs) to mouse embryonic stem (mES) cells would induce expression of pluripotency markers in the bFF nucleus. We have previously established a method to produce and specifically select multinucleated cells originated from both mES cell and bFF (bi-species heterokaryon), using indirect immunofluorescence on live cells and the combined use of imaging and sorting flow cytometry. With these tools in place, we analyzed 200 heterokaryons collected at 24, 48 and 72h after fusion, as well as unfused bFFs and mES cells, and analyzed using RNA-seq. We found significant changes in bovine gene expression patterns between bFFs and heterokaryons obtained 24h after fusion. Upregulation of early pluripotency markers OCT4 and KLF4, as well as hypoxia response genes, contrasted with downregulation of cell cycle inhibitors such as SST. The cytokine IL6, known to increase survival of early embryos in vitro, was also upregulated in heterokaryons, although its role and mechanism of action is still unclear. The cell fusion model presented here can be used to characterize early changes in somatic nuclear reprogramming, and to study the effect of different conditions during reprogramming.

sample_organism:
Bos taurus
Mus musculus

platform_organism:
Bos taurus
Mus musculus

overall_design: Five samples total. Bi-species (mouse/bovine) heterokaryons were produced and sampled at 24, 48, and 72h after fusion. Samples of mouse only and bovine only cells were harvested in parallel as controls.

first: Cristina

first: Willard

middle: H

last: Eyestone

first: Roderick

middle: V

last: Jensen


title: Extensive epigenomic integration of the glucocorticoid response in primary human monocytes and in vitro derived macrophages

summary: Glucocorticoid receptor is a transcription factor that is ubiquitously expressed. Glucocorticoids are circadian steroids that regulate a wide range of bodily functions, including immunity. Here we report that synthetic glucocorticoids affect 1035 mRNAs in isolated healthy human blood monocytes but only 165 in the respective six day-old monocyte-derived macrophages. The majority of the glucocorticoid response in monocytes concerns genes that are dynamic upon monocyte to macrophage differentiation, whereby macrophage-like mRNA levels are often reached in monocytes within four hours of treatment. Concomitantly, over 5000 chromosomal H3K27ac regions undergo remodelling, of which 60% involve increased H3K27ac signal. We find that chromosomal glucocorticoid receptor binding sites correlate with positive but not with negative local epigenomic effects. To investigate further we assigned our data to topologically associating domains (TADs). This shows that about 10% of macrophage TADs harbour at least one GR binding site and that half of all the glucocorticoid-induced H3K27ac regions are confined to these TADs. Our analyses are therefore consistent with the notion that TADs naturally accommodate information from sets of distal glucocorticoid response elements.


title: RNA sequencing to identify differences between two E. coli strains that respond differently to volatiles of Streptomyces sp.

city: Leiden

first: Mariana

last: Avalos Garcia

address: Sylviusweg 72

department: Microbial Biotechnology and Health

institute: Leiden University/Biology Institute Leiden

summary: The goals of this study are to compare the transcriptomic response of a E. coli strain with a mutation in the promotor region of the outer membrane porins regulator ompR-envZ that has an increased resistance to ammonia released by a Streptomyces strain.

overall_design: RNA from E. coli extracted during mid exponential phase

middle: A

last: Garcia

first: Gilles

middle: P

last: van Wezel


title: Expression data from newborn Alox12b knockout mouse epidermis

status: Public on Mar 01 2019

city: Heidelberg

first: Thomas

last: Hielscher

address: INF 280

department: Biostatistics

country: Germany

institute: German Cancer Research Center

summary:
Autosomal recessive congenital ichthyoses are a group of non-syndromic congenital keratinization disorders including harlequin ichthyosis, lamellar ichthyosis, and congenital ichthyosiform erythroderma with a total prevalence of 1:200,000. Affected individuals who are often born as collodion babies present with generalized scaling of the skin. This reflects a physical compensation for the defective cutaneous permeability barrier underlying all ichthyoses. Inactivity of 12R-lipoxygenase (12R-LOX) is a frequent cause of ARCI. Mice with targeted inactivation of the 12R-LOX gene Alox12b were established .Heterozygous mutant mice (Alox12b+/−) were bred with 129S6, and their heterozygous offspring were intercrossed to  obtain homozygous mutant mice. Homozygous Alox12b knockout mice died within 3 hours after birth owing to defective skin barrier function.
We used microarray to compare the gene expression profile in the epidermis of Alox12b-null mice with that of wildtype animals. Inactivation of Alox12b was associated with the upregulation of genes involved in keratinization, cholesterol biosynthesis, and Fc-epsilon receptor signaling.

overall_design: Alox12b-null mice and wildtype control mice were sacrified immediately after birth and epidermis was harvested for RNA extraction and hybridization on Affymetrix microarrays.

first: Peter

last: Krieg


title: Expression data from adult mouse epidermis upon tamoxifen induced inactivation of Alox12b

summary:
Autosomal recessive congenital ichthyoses (ARCI) are a group of non-syndromic congenital keratinization disorders including harlequin ichthyosis, lamellar ichthyosis, and congenital ichthyosiform erythroderma with a total prevalence of 1:200,000. Affected individuals who are often born as collodion babies present with generalized scaling of the skin. This reflects a physical compensation for the defective cutaneous permeability barrier underlying all ichthyoses. Inactivity of 12R-lipoxygenase (12R-LOX) is a frequent cause of ARCI. Epidermis-specific conditional knockout of Alox12b encoding 12R-LOX was established in mice using the Cre-Lox system. Tamoxifen-induced Alox12b inactivation in mouse skin caused an ichthyosis-like phenotype.
We used microarray to compare the gene expression profile in the epidermis of mice after tamoxifen induced Alox12b inactivation with that of control animals. Inactivation of Alox12b was associated with the upregulation of genes involved in keratinization, cholesterol biosynthesis, and Fc-epsilon receptor signaling.

overall_design: Alox12b inactivation in keratinocytes of 8-week old Alox12bfl/fl/K14-Cre mice was induced by repeated intraperitoneal injection of tamoxifen. Homozygous floxed littermates (Alox12bfl/fl) treated in parallel served as controls. 6 days after tamoxifen treatment the mice were sacrified and epidermis was harvested for RNA extraction and hybridization on Affymetrix microarrays.


title: nad9 knockdown 1-ANR MITOMANIP

city: evry

first: Soubigou-Taconnat

last: Ludivine

address: 2 rue gaston crémieux

department: URGV

country: France

institute: INRA

summary: rs12-04_rnanonpolya - nad9 knockdown 1 - Mitochondrial transcriptome regulation and coordination with the nucleus - Following a previously established strategy (Val et al., 2011, Nucleic Acids Res. 39, 9262–9274), we express, from an estradiol-inducible nuclear transgene, a trans-cleaving ribozyme directed against the nad9 mitochondrial mRNA and associated as a trailor sequence to a tRNA mimic. The latter serves as a shuttle and ensures mitochondrial uptake of the chimeric RNA through the natural tRNA import pathway. In mitochondria, the ribozyme triggers cleavage and degradation of the target mRNA. The impact of the nad9 mRNA knockdown on the overall plant transcriptome. Control samples correspond to plants not induced with estradiol.

overall_design: 2 dye-swap - trans-ribozyme-mediated knockdown of a specific mitochondrial rna

first: Ludivine

last: Taconnat

first: André

last: Dietrich

first: Etienne

last: Delannoy

first: Sandrine

last: Balzergue

first: Marie-Laure

last: Martin-Magniette


title: PRMT5 Modulates Splicing in Hematopoietic Stem Cells

city: Singapore

first: Ying

last: Li

state: --- Select a state ---

address: 14 Medical Dr, Singapore

country: Singapore

institute: Cancer Science Institute of Singapore

summary: This study aimed to clarify the role of PRMT5 in the hematopoietic stem cell (HSC) compartment, and elucidate the functional relevance of PRMT5-mediated splicing in HSCs. We confirm the cell intrinsic requirement for PRMT5 in HSC maintenance, and present evidence suggesting that PRMT5 deficiency perturbs HSC proteostasis. Notably, we also uncover a critical role for PRMT5 in maintaining HSC genomic integrity by modulating splicing of genes involved in DNA repair; loss of which leads to unresolved DNA damage, p53 activation and rapid HSC exhaustion. Overall, these findings establish PRMT5-mediated splicing as a major determinant of HSC fate, and highlight the need to maintain an adequate level of PRMT5 activity in HSCs.

overall_design: Hematopoietic stem cells (HSCs; Lineage-Sca-1+CD48-CD150+), isolated from Prmt5fl/fl or Prmt5Δ/Δ littermate- and gender-matched mice 7 days post-induction, were subjected to RNA-seq. HSCs for each independent sample were obtained from bone marrow cells pooled from two mice. Three independent samples were obtained for each group.

first: Qiancheng

last: Tan

first: Jia


title: RNA-seq experiment performed on activated human CD4+ T cells

city: Saint Louis

first: Anil

middle: Kumar

last: Chauhan

state: MO

address: 1402 South grant

department: Medicine

institute: Saint Louis University

summary: Analysis perfomed on four paired samples with two treatments and paired untreated sample

overall_design: We purified naïve CD45RA+CD4+ T cells from PBMCs collected from SLE patients. These cells were maintained for two days in culture medium supplementd with 20 IU of IL-2. Thereafter cells were harvetd and total RNA was purified using the kit from InVitroen. The sequencing was perfomed using Ion Torrent Kit. The RNA-seq was perfomed on Ion Torrent Sequncer.

middle: K


title: PRC2 proteins EZH1 and EZH2 regulate postnatal hepatic maturation [RNA-seq2]

city: Philadelphia

first: Jessica

middle: Mae

last: Grindheim

state: PA

address: 3400 Civic Center Blvd SCTR 9-169

department: Cell and Developmental Biology

institute: UNIVERSITY OF PENNSYLVANIA

summary: The inability to derive fully functional cell types, such as hepatocytes, from stem cells may emanate from the lack of knowledge about mechanisms that underlie postnatal cell maturation. We characterized hepatic maturation during the postnatal day 14 (P14) to 2-month-old (M2) transition and found more than 3000 genes differentially expressed. Nearly half of such maturation genes have H3K27me3 at their promoters or gene bodies at P14 or M2. Genetic ablation of both PRC2 histone methyltransferases in perinatal livers causes hepatocytes to prematurely differentiate, expressing genes at P14 that would normally be induced later, by M2. Using srHC-seq, a new method to map sonication-resistant heterochromatin, we found that the H3K27me3+ prematurely upregulated genes have euchromatic promoters at P14. We also observed derepression of many non-hepatic lineage genes with euchromatic promoter H3K27me3-marking. Thus, Polycomb repression is used to restrain expression of late liver maturation genes and lineage inappropriate genes at euchromatic promoters.

overall_design: 75 bp, single-end strand-nonspecific, polyA+ hepatocyte RNA-seq. Samples include 2 P14 Wt and 3 Ezh1 mutants

middle: M

first: Dario

last: Nicetto

first: Greg

last: Donahue

first: Kenneth

middle: S

last: Zaret


title: Ets1 modulates epigentic landscape of key TFH genes in T naïve cells

first: Chan Johng

last: Kim

summary: Ets1 can directly bind key TFH genes, regulating their expression . Loss of Ets1 results in the pre-mature expression of TFH-genes in Non-TFH cells. We wished to analyze if loss of Ets1 correlated with changes in chromatin accessibility especially in TFH gene loci.

overall_design: DNA was extracted from splenic CD4+CXCR5+PD-1+ TFH and CD4+CD44-CD62L+ T naïve cells in Ets1 fl/fl and CD4-cre Ets1 fl/fl mice and analyzed by ATAC seq.

first: Chan

first: Nurul

last: Hasan

first: Ambarnil

last: Ghosh

first: Gi-Cheon

first: Dipayan

last: Rudra

first: Sin-Hyeog

last: Im


title: Feedforward regulation of Myc coordinates lineage-specific with housekeeping gene expression during progenitor cell differentiation

city: London

first: Gopuraja

last: Dharmalingam

address: Faculty of Medicine, Imperial College, Hammersmith Hospital Campus

department: Epigenetics section

country: United Kingdom

institute: MRC London Institute of Medical Sciences

summary: Chromatin-associated RNA-Seq of pre-B cell line B3 transduced with Ikaros (Ikaros-ERt2) or Myc (Myc-ERt2) or Ikaros+Myc or control vector (Empty).

overall_design: Chromatin associated RNA from 4 or 2 biological replicates of B3 cells transduced with Ikaros, Myc, Ikaros+Myc were isolated 30, 60 and 180 min after induction with 4-OHT. Vector transduced B3 cells (ERt2-IRES-GFP)  treated with 4-hydroxytamoxifen were used as controls.

first: Isabel

middle: F

last: Vidal

first: Matthias

last: Merkenschlager


title: miRNA profiling of urinary exosomes to assess the progression of acute kidney injury

city: Miyazaki

first: Masahiro

last: Ikeda

state: Miyazaki

address: 1-1 Gakuenkibanadai-Nishi

department: Faculty of Agriculture

country: Japan

institute: University of Miyazaki, Miyazaki

summary: Because exosomes have gained attention as a source of biomarkers, we investigated if miRNAs in exosomes (exo-miRs) can report the disease progression of organ injury. Using renal ischemia-reperfusion injury (IRI) as a model of acute kidney injury (AKI), we determined temporally-released exo-miRs in urine during IRI and found that these exo-miRs could reliably mirror the progression of AKI. From the longitudinal measurements of miRNA expression in kidney and urine, we found that release of exo-miRs was regulated sorting process, rather than simply representing their intracellular biosynthesis. In the injury state, miR-16, miR-24, and miR-200c were increased in the urine. Interestingly, expression of target mRNAs of these exo-miRs was significantly altered in renal medulla. Next, in the early recovery state, urinary exo-miRs (miR-9a, miR-141, miR-200a, miR-200c, miR-429), which shares Zeb1/2 as a common target mRNA, were upregulated, indicating that they reflect TGF--associated renal fibrosis. Finally, release of exo-miRs (miR-125a, miR-351) was regulated by TGF-1 and was able to differentiate the sham and IRI even after the injured kidneys were functionally recovered. Altogether, these data indicate that exo-miRs released in renal IRI are largely associated with TGF- signaling. Temporal release of exo-miRs which share targets might be a regulatory mechanism to control the disease progression of AKI.

overall_design: The exosomal miRNA dataset was compared at the indicated times with the miRNAs differentially expressed in(side) kidneys at day 1.5, day 3, and day 14 post IRI surgery. miRNAs in kidney were analyzed using Affymetrix Transciptome Analysis Console 4.0 and the miRNAs in the IR group were selected by using a fold change threshold of at least 2 and a nominal P value cutoff of 0.05 in comparison with the sham group (n = 3 for each group at each time point).

first: Hiroko

last: Sonoda

first: Ki-Hoon

last: Park

first: Deepak

last: Nihalani

first: Je-Hyun

last: Yoon

first: Sang-Ho

last: Kwon


title: Gene expression from mouse lung adenocarcinoma-associated CD4 cells

city: Frederick

first: NA-YOUNG

last: SONG

state: MD

address: 1050 Boyles Street

institute: NCI

summary: Comparison of gene expression of mouse lung adenocarcinoma-associated CD4 cells isolated from C57BL/6 mice injected with Kras-CL and Kras IKKa low cells

overall_design: Lung tissues were collected at 1.5 months after cell injection. Then CD4+ cells were isolated using magnetic beads. Total RNAs from CD4+ cells were extracted using Trizol and then subjected to hybridization for Affymetrix microarray.

first: Na-Young

last: Song

first: Yinling

last: Hu


title: Expression data from Saccharomyces cerevisiae carrying the dis3E729K mutation

city: Vancouver

first: Peter

last: Stirling

state: BC

address: 675 W 10th Ave

department: Terry Fox Laboratory

country: Canada

institute: BC Cancer Research Centre

summary:
Dis3 is a 3'-5' exonuclease and endonuclease that is conserved from bacteria to humans, and participates in the processing and degradation of many RNA species. DIS3 mutants suffer from impaired RNA processing, defective microtubules, growth retardation, and temperature sensitivity; however, the mechanisms by which DIS3 mutations influence cell cycle-related phenotypes remains largely unknown.
Since the major impact of Dis3 mutation should be on the transcriptome, we performed an expression microarray on dis3E729K in order to elucidate the expression consequences of this allele.

platform_organism:
Schizosaccharomyces pombe
Saccharomyces cerevisiae

overall_design: Strains were cultured at permissive conditions (30°C) in synthetic drop-out media selecting for the allele of interest. The wildtype control strain, as well as the mutant, both carry a URA3 marker adjacent to the DIS3 gene. Expression microarray was performed on mid-log phase culture samples. All experiments were conducted in duplicate.

first: Karissa

last: Milbury

first: Zongli

last: Luo

first: Claire

last: Fowler

first: Biplab

last: Paul

first: Ben

last: Montpetit


title: Effect of SARM1 deficiency on mouse brain transcriptome with or without prion infection

city: Zurich

first: Caihong

last: Zhu

address: Schmelzbergstrasse 12

country: Switzerland

institute: Institute of Neuropathology

summary: To study the effect of SARM1 deficiency on brain transcriptome, we performed RNAsequencing of the brain of SARM1-/- mice and their wild type (C57BL/6J) littermates with or without prion infection. We analyzed differential gene expression.

overall_design: RNAsequencing on brain mRNA of SARM1-/- and wild type littermates (2 month-old for uninfected, 6 month-old for prion-infected, n=4 per genotype).


title: Dihydrotestosterone induces minor transcriptional alterations in genital skin fibroblasts of normal prepubertal boys

city: Setagaya-ku, Okura

first: Kanako

last: Tanase-Nakao

state: Tokyo

institute: National Center for Child Health and Development

summary: Endogenous and exogenous androgens induce masculinization of external genitalia through binding to the androgen receptor (AR). Although several efforts were made to determine the androgen target genes in external genitalia by analyzing transcript profiles in cultured genital skin fibroblasts, no genes except for APOD were shown to be significantly regulated by androgens. In the present study, we performed microarray analysis for genital skin fibroblasts obtained from four boys with buried penis (the control individuals) and a patient with androgen insensitivity syndrome (AIS) due to a hypomorphic mutation in AR (the AIS patient). We identified 26 transcripts which were upregulated or downregulated by dihydrotestosterone (DHT) in all samples of control individuals and, to a lesser extent, in the sample of the AIS patient. None of the transcripts showed statistically significant differences between DHT-treated and -untreated samples. The 26 transcripts included CYP1B1, a gene possibly involved in the development of genital tubercle in mice, and APOD, as well as several genes that have been reported as androgen targets in prostate or other tissues. Realtime PCR analyses detected a significant difference in the effects of DHT on APOD expression between the AIS patient and the control individuals, while the difference in the fold changes of CYP1B1 expression were negligible. The results of this study indicate that DHT mediates masculinization of external genitalia through minor transcriptional changes of several genes, rather than massive changes in specific genes. In addition, our data confirm the clinical importance of APOD as a biomarker for AR function.

overall_design: We analyzed genital skin fibroblasts obtained from four boys with apparently normal AR activity (the control individuals) and one patient with DSD and a hemizygous p.Ala597Thr mutation in AR (the AIS patient).

first: Kentaro

last: Mizuno

first: Yutaro

last: Hayashi

first: Yoshiyuki

last: Kojima

first: Mariko

last: Hara

first: Kenji

last: Matsumoto

first: Matsubara

last: Yoichi

first: Maki

last: Igarashi

first: Mami

last: Miyado

last: Fukami


title: Axl targeting in experimental unilateral ureteral obstruction

city: Bergen

first: Tomasz

last: Stokowy

address: Nygardsgaten 5

department: IT Division

country: Norway

institute: University of Bergen

summary: We investigated if Axl receptor tyrosine kinase was up-regulated in unilateral ureteral obstruction (UUO) and if blocking of Axl by a small molecule called BGB324 (also called Bemcentinib) reduces fibrosis development in the ligated kidney as compared to treatment with its vehicle alone.

overall_design: Two treatment groups of C57Bl/6JOaHSD mice (both groups n=6), which were treated with either BGB324/Bemcentinib or its vehicle (0.5% hydroxylpropyl-methylcellulose in 0.1% Tween 80).

first: Lea

last: Landolt

first: Andreas

last: Scherer

first: Hans

last: Marti


title: matr knockdown 1-ANR MITOMANIP

first: Soubigou-Taconnat

last: Ludivine

summary: rs12-06_a9-mrnonpolya - matr knockdown 1 - Mitochondrial transcriptome regulation and coordination with the nucleus - Following a previously established strategy (Val et al., 2011, Nucleic Acids Res. 39, 9262–9274), we express, from an estradiol-inducible nuclear transgene, a trans-cleaving ribozyme directed against the matR mitochondrial mRNA and associated as a trailor sequence to a tRNA mimic. The latter serves as a shuttle and ensures mitochondrial uptake of the chimeric RNA through the natural tRNA import pathway. In mitochondria, the ribozyme triggers cleavage and degradation of the target mRNA. The impact of the matR mRNA knockdown on the overall plant transcriptome. Control plants express either no ribozyme (C0a and C0b) or the shuttle RNA combined with a ribozyme that has no specific target in A. thaliana (SD).

sample_organism:
Arabidopsis thaliana
Cephalanthera damasonium

overall_design: 6 dye-swap - trans-ribozyme-mediated knockdown of a specific mitochondrial rna

first: Ludivine

last: Taconnat

first: André

last: Dietrich

first: Etienne

last: Delannoy

first: Sandrine

last: Balzergue

first: Marie-Laure

last: Martin-Magniette


title: RNAseq of Islet CD11c+ cells and Islet T cells from 12-20 week non-obese diabetic mice

city: Denver

first: Rachel

last: Friedman

state: Colorado

address: 1400 Jackson

institute: National Jewish Health

summary: Using intravital 2-photon islet imaging we show that T cell extravasation into the islets is an extended process, with T cells arresting in the islet vasculature in close proximity to perivascular CD11c+ cells. Antigen is not required for T cell trafficking to infiltrated islets, but T cell chemokine receptor signaling is necessary. Using RNAseq, we show that islet CD11c+ cells express over 20 different chemokines that bind chemokine receptors expressed on islet T cells.

overall_design: CD11c+ cells (DAPI-CD45+CD19-CD90.2-CD11c+MHCII+) and T cells (DAPI-CD45+CD90.2+) were FACS sorted from 4-8 pooled 12-20 week non-obese diabetic (NOD) mice per replicate, 4 replicates for CD11c cells and 5 replicates for T cells.

first: Adam

last: Sandor

first: Robin

last: Lindsay

first: Nathan

last: Dyjack

first: Jennifer

middle: C

last: Whitesell

first: Cydney

last: Rios

first: Max

last: Seibold


title: DRomics: a turnkey tool to support the use of the dose-response framework for OMICs data in ecological risk assessment

city: Leipzig

first: Stefan

last: Scholz

address: Permoserstr. 15

department: Bioanalytical Ecotoxicology

institute: Helmholtz Centre for Environmental Research

summary: Omics approaches (e.g. transcriptomics, metabolomics) are promising for ecological risk assessment (ERA) since they provide mechanistic information and early warning signals. A crucial step in the analysis of omics data is the modelling of concentration-dependency which may have different trends including monotonic (e.g. linear, exponential) or biphasic (e.g. U shape, bell shape) forms. The diversity of responses raises several challenges concerning modelling and effect concentration (EC) derivation.  Furthermore, handling high-throughput datasets is time-consuming and requires effective and automated processing routines. Thus, we developed a freely available tool (DRomics, available as an R-package and as a web-based service) which, after elimination of molecular responses (e.g. differential gene expressions from microarrays) with no concentration-dependency and/or high variability, identifies the best model for concentration-response curve description. Subsequently, an effect concentration (e.g. a benchmark dose) is estimated from each curve and curves are classified based on their model parameters. This tool is especially dedicated to manage data obtained from an experimental design favoring a great number of tested doses rather than a great number of replicates and also to handle properly monotonic and biphasic trends. The tool finally restitutes a table of results that can be directly used to perform ERA approaches.

overall_design: Scenedesmus vacuolatus cultures were exposed for 14 hours to five concentrations of triclosan (0.690, 1.22, 2.15, 3.77 and 6.63µg/L) and one solvent control (final DMSO concentration of 0.1 %) with 5 replicates. After sampling, the RNA was extracted, labelled and hybridised to an Agilent one-color array.

first: Floriane

last: Larras

first: Elise

last: Billoir

first: Vincent

last: Baillard

first: Aurelie

last: Siberchicot

first: Tesfaye

last: Wubet

first: Mikka

last: Tarka

first: Mechthild

last: Schmitt-Jansen

last: Delignette-Muller


title: ICH Induces Monocyte-Related Gene Expression Within Six Hours; A Study of Global Transcriptional Profiling in Swine ICH

city: Cincinnati

first: Xiaoting

last: Zhu

state: OH

address: 3333 burnet avenue,MLC7024

institute: Cincinnati Children's Hospital Medical Center

summary: Intracerebral hemorrhage (ICH) is a severe neurological disorder with no proven treatment. Our prior research identified a significant association with monocyte level and ICH mortality. To further advance our understanding, we sought to identify the gene expression changes after ICH using a swine model to test the hypothesis that ICH would result in changes in peripheral blood mononuclear cell (PBMC) gene expression.  There were 182 significantly upregulated and 153 significantly down-regulated DEGs after ICH. Consistent with findings in humans, significant GO and KEGG pathways were those primarily related to inflammation, immune response, and response to infectious pathogens. There were five genes, all with increased expression post-ICH, that were repeatedly identified as significant DEGs in the statistically significant KEGG pathways:  CD14 (cluster of differentiation 14), TLR4 (toll-like receptor-4), CXCL8 (CXC motif chemokine-8), IL-18 (interleukin-18), and CXCL2 (CXC motif chemokine-2).  Conclusion:  ICH induced changes in PBMC gene expression within 6 hours of onset. DEGs that were highly expressed in the significant biological pathways included those related to inflammation, the immune response, and, more specifically, monocyte activation. Further research is needed to determine if these changes affect outcomes and may represent new therapeutic targets.

overall_design: In 10 pigs with autologous blood injection to induce ICH, two PBMC samples were drawn from each pig with the first immediately prior to ICH induction and the second 6 hours later. RNA-seq was performed to identify differentially expressed genes (DEGs) and associated Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways.

first: Kyle

middle: B

last: Walsh

first: Xiang

last: Zhang

first: Eric

last: Wohleb

first: Daniel

last: Woo

first: Long

last: Lu

first: Opeolu

last: Adeoye


title: Peri-sinusoidal stromal cells form a unique multispecific niche for hematopoietic stem cells and early B cells

city: Marseille

first: Stéphane

middle: JC

last: Mancini

address: 27 Boulevard Lei Roure

department: Centre de Recherche en Cancérologie de Marseille

institute: INSERM

summary: In the bone marrow, CXCL12 and IL7 are essential for B cell differentiation whereas hematopoietic stem cells (HSC) maintenance requires SCF and CXCL12. Previous studies, including ours, indicate that peri-sinusoidal stromal (PSS) cells are heterogeneous and that part of them express and are the main source of IL7. Our single cell qPCR and transcriptomic analysis demonstrate that SCF, CXCL12 and IL7 are co-expressed by a unique peri-sinusoidal stromal cell subset.

overall_design: CD45-CD51+BP1+ peri-sinusoidal stromal cells, CD45-CD51+BP1- mesenchymal cells and CD45-CD31+ endothelial cells were sorted and mixed together


title: Pre-clinical evaluation of cysteamine bitartrate as a therapeutic agent for mitochondrial respiratory chain disease (human)

first: Zhe

address: Translational Research Lab

institute: University of Pennsylvania

summary: Pre-clinical studies of cysteamine bitartrate demonstrate its narrow therapeutic window, where toxicity at millimolar levels correlates with a marked induction of hydrogen peroxide production.  At micromolar range concentrations, cysteamine bitartrate yielded a survival benefit in RC disease subject fibroblasts, and protection from brain death in RC complex IV deficient zebrafish.  Mitochondrial oxidative stress and membrane potential were significantly improved by micromolar cysteamine bitartrate in RC complex I disease worms, translating to a modest improvement of animal development and fecundity but not lifespan.  Overall, these data suggest that cysteamine bitartrate may hold therapeutic potential but requires careful consideration of safe and effective dose to further evaluate in clinical trials of human subjects with primary mitochondrial disease.

overall_design: Rrimary human fibroblast cell lines (FCLs) derived from genetically-confirmed RC complex I NDUFS8 deficient and multiple RC deficient FBXL4 disease human subjects; treated with cysteamine for 6 or 24 hours.

first: Marni

last: Falk

first: Erzsebet

last: Polyak

first: Min

last: Peng


title: Pre-clinical evaluation of cysteamine bitartrate as a therapeutic agent for mitochondrial respiratory chain disease (worm)

overall_design: One wild type group, one untreated Gas-1 mutant group, one Gas-1 + Nacetylcysteine group, and 4 Gas-1 + Cysteamine groups using different dosages


title: Characterization of Stathmin role in normal and  Δ16HER2-transformed mouse mammary gland

city: Aviano

first: Riccardo

last: Bomben

address: Via Franco Gallini 2

department: D-RT

country: Italy

institute: CRO Aviano

summary: Stathmin 1 is a microtubules (MT)-destabilizing protein and, as such, it is critically involved in the regulation of mitosis, vesicular trafficking and cell motility. Since the integrity of the mammary gland relies on the maintenance of oriented cell division and apico-basal polarity and the preservation of these characteristics is essential for mammary gland functionality and for preventing breast cancer, it is important to evaluate the role of stathmin in this context.

overall_design: GEP experiments were performed in mouse mammary glands collected from pre-neoplastic 13 weeks-old WT and STM KO Δ16HER2 transgenic female mice, with Agilent platform. Bioinformatics analyses were performed by Gene Springs

first: Ilenia

last: Segatto

first: Francesca

last: Citron

first: Gustavo

last: Baldassarre

first: Barbara

last: Belletti


title: Transformation of megakaryocyte-erythroid progenitors to acute myeloid leukemia-initiating cells: Cut&Run

city: Houston

first: Daisuke

last: Nakada

state: Texas

address: One Baylor Plaza

department: Molecular and Human Genetics

institute: Baylor College of Medicine

summary: Oncogenic mutations confer aberrant replicative capacity to cells with little or no replicative capacity, generating cancer stem cells that perpetuate the tumor through extensive self-replication and differentiation blockade. However, whether oncogenes disrupt the cellular identity of cancer stem cell by altering the developmental potential is unknown. Fate conversion has been demonstrated by ectopic expression of master transcriptional regulators, such as PU.1 and C/EBPα that confers myeloid cell fate to other cell types, and PRDM16 that confers brown adipose fate to white adipocytes or myoblasts. Here we show that a transcriptional regulator overexpressed in human myeloid malignancies, PRDM16s, causes oncogenic fate conversion, by transforming cells fated to form platelets and erythrocytes into myeloid leukemia-initiating cells (LICs). Prdm16s expression in murine hematopoietic progenitor cells caused a myelodysplastic syndrome (MDS)-like disease that progressed to acute myelogenous leukemia (AML). The myeloid diseases caused by Prdm16s exhibited expansion of megakaryocyte-erythroid progenitors (MEPs) but not granulocyte-macrophage progenitors. MEPs from Prdm16s-induced leukemia possessed LIC potential, and expression of Prdm16s in normal MEPs was sufficient to convert them to myeloid LICs and blocked megakaryocytic/erythroid potential. Prdm16s induced the expression of myeloid master regulators, including PU.1 and C/EBPα, by interacting with their super enhancers. Ablation of myeloid master regulators attenuated the myeloid potential and reinstalled the megakaryocytic/erythroid potential of leukemic-MEPs in mouse models and in human AML with PRDM16 rearrangement. Our study demonstrates that oncogenic PRDM16 expression converts the fate of MEPs to a malignant myeloid fate by activating myeloid master transcription factors.

overall_design: Cut&Run profiling of FLAG-tagged Prdm16s binding sites in leukemic MEP cells, using two antibodies.

first: Kevin

last: Hoegenauer

first: Tianyuan

last: Hu


title: Translation Regulation of the Prolactin Receptor Defines Sexually Dimorphic Pain Responses to Prolactin

city: Richardson

first: Theodore

last: Price

state: TX

address: 800 W Campbell Rd.

institute: University of Texas at Dallas

summary: Transcriptional control by gonadal hormone nuclear receptors is the foundation for sex-dependent physiological processes, including pain. Our current findings point to sex-dependent translation control as a new mechanism for sexual dimorphisms in pain. We show that hindpaw or spinal administration of exogenous prolactin (PRL) induces thermal and mechanical hyperalgesia in a female-selective fashion. Unexpectedly, PCR and transcriptomic analysis of hindpaw and dorsal root ganglion (DRG) tissues reveal no differences in PRL receptor (Prlr) mRNA between sexes. Variance in overall hindpaw and DRG transcriptomes between females and males were minor. We find that Prlr mRNA and protein is mainly expressed by peptidergic nociceptors as shown by profiling using Prlr reporter mice and electrophysiology, but there are far more peptidergic neurons with functional Prlr in females than in males. In line with this, exogenous PRL increased excitability only in female neurons. Moreover, in male DRG neurons, 6-24 hr estrogen exposure establishes PRL sensitivity in Prlr mRNA+ male neurons that do not show PRL responses under other conditions. PRL-induced behavioral hypersensitivity as well as sensitivity to PRL in female DRG neurons can be ablated by treatment with cap-dependent translation inhibitor  4EGI-1. Spinal cord immunohistochemistry of Prlr reporter mice highlight that Prlr protein is only found in female DRG neurons, but Prlr mRNA localizes to central terminals of male and female sensory neurons. Based on these findings, we propose a novel mechanism for sex-dependent regulation Prlr mRNA translation that renders female DRG neurons uniquely responsive to PRL.

overall_design: Paw and DRG tissue from 3 males and 3 females are sequenced

first: Mayur

last: Patil

first: Anahit

last: Hovhannisyan

first: Jennifer

last: Mecklenburg

first: Yi

last: Zou

first: Andi

last: Wangzhou

first: Vincent

last: Goffin

first: David

last: Grattan

first: Ulrich

last: Boehm

first: Zhao

last: Lai

first: Gregory

last: Dussor

first: Armen

middle: N

last: Akopian


title: Pre-clinical evaluation of cysteamine bitartrate as a therapeutic agent for mitochondrial respiratory chain disease

first: Zhe

last: Zhang

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

sample_organism:
Caenorhabditis elegans
Homo sapiens

platform_organism:
Caenorhabditis elegans
Homo sapiens

overall_design: Refer to individual Series


title: Transformation of megakaryocyte-erythroid progenitors to acute myeloid leukemia-initiating cells: CRISPR drop-out screen

overall_design: CRISPR drop-out screen of leukemic MEP cells, consisting of four control samples and two post-selection samples.


title: Transformation of megakaryocyte-erythroid progenitors to acute myeloid leukemia-initiating cells: RNA-seq

overall_design: RNA-seq of whole bone marrow and MEP populations. Each population with two treatment groups (wild-type and Prdm16s-expressing), and each treatment subpopulation with three replicates.


title: Transformation of megakaryocyte-erythroid progenitors to acute myeloid leukemia-initiating cells: ATAC-seq

overall_design: ATAC-Seq on three wild-type MEP samples and two leukemic-MEP samples


title: Transformation of megakaryocyte-erythroid progenitors to acute myeloid leukemia-initiating cells: ChIP-seq

overall_design: ChIP-seq of two histone modifications (H3K4me3, H3K27ac) in two cell populations (wild-type MEP, Prdm16s-expressing MEP).


title: Transformation of megakaryocyte-erythroid progenitors to acute myeloid leukemia-initiating cells


title: PRC2 proteins EZH1 and EZH2 regulate postnatal hepatic maturation [RNA-Seq]

first: Jessica

last: Grindheim

summary: The inability to derive fully functional cell types, such as hepatocytes, from stem cells may emanate from the lack of knowledge about mechanisms that underlie postnatal cell maturation. We characterized hepatic maturation during the postnatal day 14 (P14) to 2-month-old (M2) transition and found more than 3000 genes differentially expressed. Nearly half of such maturation genes have H3K27me3 at their promoters or gene bodies at P14 or M2. Genetic ablation of both PRC2 histone methyltransferases in perinatal livers causes hepatocytes to prematurely differentiate, expressing genes at P14 that would normally be induced later, by M2. Using srHC-seq, a new method to map sonication-resistant heterochromatin, we found that the H3K27me3+ prematurely upregulated genes have euchromatic promoters at P14. We also observed derepression of many non-hepatic lineage genes with euchromatic promoter H3K27me3-marking. Thus, Polycomb repression is used to restrain expression of late liver maturation genes and lineage inappropriate genes at euchromatic promoters.

overall_design: 75 bp, single-end, strand-specific, polyA+ hepatocyte RNA-seq. Samples include a time course of Wt and Ezh1/2 mutants at P14 and M2.

first: Dario

last: Nicetto

first: Greg

last: Donahue

first: Kenneth

last: Zaret


title: Kidney micro-organoids generated in suspension culture

city: Parkville

first: Andrew

last: Lonsdale

state: VIC

address: 50 Flemington Rd

country: Australia

institute: Murdoch Children's Research Institute

summary: Kidney organoids have potential uses in disease modelling, drug screening and regenerative medicine. However, novel cost-effective techniques are needed to enable scale-up production of kidney cell types in vitro. We describe here a modified suspension culture method for the generation of kidney micro-organoids from human pluripotent stem cells. Each micro-organoid contains 6-10 nephrons surrounded by endothelial and stromal populations. Single cell transcriptional profiling confirmed the presence and transcriptional equivalence of all anticipated renal cell types consistent with a previous organoid culture method. Ligand-receptor mapping identified TGFβ signalling between stromal and epithelial cell types as likely to result in fibrotic changes observed with long-term culture. The addition of an ALK4 inhibitor suppressed stromal expansion, maintaining epithelial morphology and improving maturation. This suspension culture micro-organoid methodology resulted in a 3-4-fold increase in final cell yield compared to static culture, thereby representing an economical approach to the production of kidney cells for various biological applications.

overall_design: Single cell RNA-seq from a pool of kidney micro-organoids.

first: Santhosh

last: Kumar


title: Changes in CD34 and Erythroid Progenitor Transcriptome After RUNX3 Kock-down

city: Charlottesville

first: Adam

last: Goldfarb

state: Virginia

address: 415 Lane Road

department: Pathology

institute: University of Virginia

summary: The associated publication describes a RUNX3-dependent defect in primary human CD34+ HSPC differentiation into the erythroid lineage. This study was designed to determine which genes are potential targets of RUNX3, and could contribute to regulation of erythropoiesis.

overall_design: Undifferentiated human CD34+ HSPCs were subjected to lentiviral knock-down of RUNX3. After selection, cells were either harvested as undifferentiated CD34+ cells, or grown for 24 hours in erythroid medium and then harvested. Samples underwent processing using the Qiagen RNeasy kit, and RNA was quantified using a Thermo Fisher Scientific Nanodrop One spectrophotometer. Sequencing was performed by Hudson Alpha Genomic Services Laboratory (ribosomal reduction, 100bp, paired-end, 50M reads, strand-specific) and data processing was performed using Galaxy Suite tools. Analysis across the three biological replicates included comparisons between erythroid and undifferentiated cells, as well as empty vector compared to RUNX3 knock-down in both erythroid and undifferentiated cells.

first: Peter

last: Balogh


title: PRC2 proteins EZH1 and EZH2 regulate postnatal hepatic maturation [ChIP-Seq]

city: Philadelphia

address: 3400 Civic Center Blvd SCTR 9-169

institute: UNIVERSITY OF PENNSYLVANIA

overall_design: H3K27me3 ChIP in time-course of P14 and M2 hepatocytes. P14 replicates include 2 male and 2 female.


title: Gene Expression Analysis of  metastatic CRPC cell line C4-2B treated with the dual BET-kinase inhibitor MA4-022-1

city: St. Louis

first: Kiran

last: Mahajan

state: Missouri

address: CB 8242 600 South Euclid Ave

department: Surgery

institute: Washington University

summary:
We identified BRD4 as an epigenetic regulator of  the prostate lineage specific gene HOXB13  during progression of the disease from an androgen
dependent to an androgen independent state.

overall_design:
The design was to identify novel genes that are essential for CRPC growth and
treaan be targeted with MA4--022-1


title: Identification of HOXB13 target genes responsive to BET inhibitors

overall_design: Integrative analysis- we compared genes whose expression was significantly impacted either (up or downregulated) as a result of  HOXB13 knockdown  and were also sensitive to BET inhibition

first: Ranjan

last: Perera


title: Specific inhibition of DPY30 activity by peptides suppresses blood cancer cell growth

city: Birmingham

first: Kushani

last: Shah

state: AL

address: 1825 University Blvd.

department: Biochemistry & Molecular Genetics

institute: University of Alabbama at Birmingham

summary: Epigenetic modulators are being recognized as attractive targets for potential cancer treatment. SET1/MLL complexes are the major H3K4 methyltransferase complexes in mammals. The DPY30 subunit is associated with these complexes by forming a dimer that directly binds to the ASH2L subunit in the complexes and facilitates methylation. We have previously established an important role of DPY30 in certain hematologic malignancies including MLL-rearranged leukemia and Burkitt’s lymphoma, but the domain on DPY30 that regulates cancer growth is not evident. Moreover, the potential of pharmacologically targeting this chromatin modulator to inhibit cancer has not been explored. Here we have developed a peptide-based strategy to specifically target DPY30 activity. We have designed cell-penetrating peptides that can either bind to DPY30 or show defective or enhanced binding to DPY30. The DPY30-binding peptides, but not the non-binding peptide, inhibit DPY30’s activity in interacting with ASH2L and in enhancing H3K4 methylation. Treatment with the DPY30-binding, but not the non-binding, peptide significantly inhibited the growth of MLL-rearranged leukemia and other MYC-dependent hematologic cancer cells including Burkitt’s lymphoma cells. These results strongly support a critical role of the ASH2L-binding groove of DPY30 in promoting the growth of certain blood cancers, and also demonstrate a proof-of-principle for the feasibility of pharmacologically targeting the ASH2L-binding groove of DPY30 for potential cancer inhibition.

overall_design: Samples are RNA-seq from peptide treated cancer cell lines. Y518R peptide binds DPY30 while 3R peptide does not bind DPY30.

first: Robert

last: Whitaker

first: Theodore

last: Busby

first: Jing

last: Hu

first: Bi

last: Shi

first: Zhenjia

last: Wang

first: Chongzhi

last: Zang

first: William

last: Placzek

first: Hao

last: Jiang


title: PRC2 proteins EZH1 and EZH2 regulate postnatal hepatic maturation

first: Jessica

last: Grindheim


title: RNAi-dependent Polycomb repression controls transposable elements in Tetrahymena [RNA-seq]

city: Ann Arbor

first: Fengbiao

last: Mao

state: Michigan

address: 1301 Catherine St

department: Department of Pathology

institute: University of Michigan

summary: RNA interference (RNAi) and Polycomb repression play evolutionarily conserved and often coordinated roles in transcriptional silencing. Here we show that in the protozoan Tetrahymena thermophila, germ line-specific internally eliminated sequences (IES) - many related to transposable elements (TE) - are transcriptionally activated in mutants deficient in the RNAi-dependent Polycomb repression pathway. Mobilization of recently duplicated TE also dramatically increases in these mutants. Importantly, transcriptional silencing and activation of TE-related sequences are accompanied by switching between noncoding RNA (ncRNA) and mRNA production, which can be affected by co-transcriptional processing as well as RNAi and Polycomb repression. We posit that interplay between RNAi and Polycomb repression is a widespread phenomenon, whose ancestral role is epigenetic silencing of TE.

overall_design: RNA-seq profiling of Tetrahymena thermophila cells (wild-type, DCL1KO, EZL1KO, and PDD1KO) at different conjugation stages (3, 6, and 10 hours post-mixing).

first: Yifan

last: Liu


title: RNAi-dependent Polycomb repression controls transposable elements in Tetrahymena [small RNA-seq]

type: Non-coding RNA profiling by high throughput sequencing

summary: RNA interference (RNAi) and Polycomb repression play evolutionarily conserved and often coordinated roles in transcriptional silencing. Here we show that in the protozoan Tetrahymena thermophila, germ line-specific internally eliminated sequences (IES)—many related to transposable elements (TE)—are transcriptionally activated in mutants deficient in the RNAi-dependent Polycomb repression pathway. Mobilization of recently duplicated TE also dramatically increases in these mutants. Importantly, transcriptional silencing and activation of TE-related sequences are accompanied by switching between noncoding RNA (ncRNA) and mRNA production, which can be affected by co-transcriptional processing as well as RNAi and Polycomb repression. We posit that interplay between RNAi and Polycomb repression is a widespread phenomenon, whose ancestral role is epigenetic silencing of TE.

overall_design: Small RNA-seq profiling of Tetrahymena thermophila cells (wild-type, DCL1KO, EZL1KO, and PDD1KO) at late conjugation (10 hours post-mixing).


title: Illumina HiSeq Sequencing on Breast cancer PDX samples

city: Salt Lake City

first: Alana

last: Welm

state: utah

address: 2000 Cir of Hope Dr

institute: Huntsman cancer institute

summary: RNAseq was done on Breast cancer PDX samples uisng Library protocol =llumina TruSeq Stranded Total RNA Kit with Ribo-Zero Gold , HiSeq 50 Cycle Single-Read Sequencing v4

overall_design: Single Readsequencing of PDX samples


title: Gene expression after depletion of fast cycling cells by heat shock, hydroxyurea, or colchicine treatment in the Sf-1 thermosensitive Hydra strain.

city: Geneva

first: Yvan

last: Wenger

state: Geneva

address: 30 Quai Ernest-Ansermet

department: Genetics and Evolution

institute: University of Geneva

summary: Treatments targetting fast cycling cells were applied to Hydra in order to: 1. identify compensatory gene expression behaviours after loss of neurogenesis, 2. improve the detection of cell-type expression for all transcripts in Hydra, together with the dataset entitled “Gene expressions in the three Hydra stem cell populations”. The processed data deposited here are also accessible in a graphical manner from a blast-based web interface available at https://hydratlas.unige.ch

overall_design:
Animals from the thermosensitive mutant strain Hydra Sf-1 (also called Hydra magnipapillata A9) were subjected to heat shock, hydroxyurea, or colchicine treatment and were sampled 9 (colchicine, heat shock) or 11 days (hydroxyurea) after the beginning of the treatment. In addition, animals treated with hydroxurea were sampled at 4, 5, and 7 days after the beginning of the treatment. Central body columns were used for sequencing. Most conditions are represented by 3 or 4 replicates.
>> Grant Information <<
Awarded to Dr. Brigitte Galliot:
- Swiss National Science Foundation (SNF grant 31003A-130337,
31003A_149630 & 31003_169930)
- NCCR Frontiers in Genetics, Stem Cells & Regeneration project
- The Canton of Geneva
- The Claraz donation
- Human Frontier Science Program (HFSP RHP0016-2010)

first: Wanda

last: Buzgariu

first: Brigitte

last: Galliot


title: Gene expression time course analysis during apical and basal regeneration in Hydra

summary: After section, Hydra regenerate each missing part within 2 to 3 days. This study was designed to allow tracking of gene expression levels during apical and basal regeneration and to compare these different regenerative contexts systematically. We determine that transient early genetic events are generic, i.e. that modulations in gene expression have analogous directions, magnitudes and durations whatever the level along the central body column and orientation of the amputation plane. In turn, early modulated transcripts with sustained expression patterns during regeneration are generally distinct during apical and basal regeneration. Genes that were previously shown to be instrumental in defining the apical organizer (Wnt signalling pathway) are among the first genes to be expressed in the condition where Hydra regenerates its apical part, Wnt3 is actually the only detected transcript encoding a signalling protein already upregulated by 2h. Regarding basal regeneration, we identify a number of transcripts with sustained expression patterns already established by 4h, some of them encoding evolutionary conserved signalling proteins, which are almost exclusively consisting of agonists and antagonists of the BMP signalling pathway. The processed data deposited here are also accessible in a graphical manner from a blast-based web interface available at https://hydratlas.unige.ch

overall_design:
Samples were taken from regenerating tips of Hydra regenerating apical regions from the 50% (mid-gastric position) or the 80% level (i.e. after decapitation), as well as basal-regenerating tips from the 50% position. Data were sampled at 0, 0.5, 1, 2, 4, 8, 16, 24,36,48 hours post section. In addition, intact animals, apical regions (head), and basal regions (basal disk and lower part of the peduncle) were sampled in homeostatic condition. All samples were produced in biological triplicates from tissue originating from 20 to 25 animals.
>> Grant Information <<
Awarded to Dr. Brigitte Galliot:
- Swiss National Science Foundation (SNF grant 31003A-130337,
31003A_149630 & 31003_169930)
- NCCR Frontiers in Genetics, Stem Cells & Regeneration project
- The Canton of Geneva
- The Claraz donation
- Human Frontier Science Program (HFSP RHP0016-2010)


title: Generic and context-dependent gene modulations during Hydra whole body regeneration

overall_design: Refer to individual Series


title: Identification of circRNA Expression Signatures for breast cancer metastasis

city: Nanjing

first: shouyu

last: wang

address: 22 Hankou Road

country: China

institute: Nanjing university medical school

summary: To identify breast cancer metastasis-relevant circRNAs, we assessed the expression profiles of circRNAs in parental MDA-MB-231 (231-PAR) cells, isogenic brain metastatic cells (231-BM6), lung metastatic cells (LM2) and bone metastatic cells (1833), which were isolated from brain, lung or bone-seeking 231-PAR cells

overall_design: LncRNA Expression profiling analysis of the 231-PAR, 231-BM6, LM2, 1833 cells by Arraystar Human circRNA Array v2.

first: Shouyu


title: Identification of DAF-16/FoxO targets associated with longevity

first: Richard

last: McEachin

state: United States

address: 2800 Plymouth Road

department: DCM&B

summary: FoxO transcription factors can promote longevity in invertebrates and mammals. In C.elegans, the FoxO family member DAF-16 is required for lifespan extension in the contexts of daf-2/IGFR mutation and germline ablation.  The daf-16 genomic locus encodes three distinct groups of transcripts (a,b, and d/f/h).  In animals with reduced insulin signaling or ablated germlines, mutations that reduce daf-16a and d/f/h levels without affecting daf-16b reduce lifespan to the same extent as daf-16 null mutations. We reasoned that identifying a set of targets of the daf-16a and d/f/h isoforms that are differentially regulated in two contexts of reduced insulin signaling and in germline ablated animals would enrich for the daf-16 transcriptional targets that are required for longevity.  We identified targets that were differentially regulated in daf-2(e1368) and daf-2(e1370) mutants relative to wild-type, and differentially regulated  in the opposite direction from WT  in compound mutants with both daf-16(mg54), which eliminates the a and d/f/h isoforms, and daf-16(mu86) which is a predicted null allele. We performed a similar analysis in glp-1(e2141) germline ablated animals (omitting the wild-type comparison).  We then identified daf-16 targets associated with longevity (dal genes) which were found in all three sets of comparisons.

overall_design: 10 strains were profiled, with 5 biological samples of each strain, for a total of 50 samples.  Synchronized populations were grown to day 1 of adulthood, then harvested for RNA.  Animals were grown at 15C for the first 72 hours to permit dauer bypass, then upshifted to 20C, except for glp-1 strains which were grown at 25C to ablate the germline.  Lifespan analysis was performed on a cohort from each sample to confirm expected phenotypes. Strains were wild-type (WT), daf-2(e1370), daf-16(mg54);daf-2(e1370), daf-16(mu86);daf-2(e1370), daf-2(e1368), daf-16(mg54);daf-2(e1368), daf-16(mu86);daf-2(e1368), glp-1(e2141), daf-16(mg54);glp-1(e2141), daf-16(mu86);glp-1(e2141).

first: Tzong-Yang

last: Chen

first: Patrick


title: Gene expressions in the three Hydra stem cell populations

summary: Transgenics Hydra expressing eGFP in interstitial stem-cells (ISC), gastrodermal epithelial cells (gESC) or epidermal epithelial cells (eESC) were used to sort these populations of stem cells by Fluorescence activated cell sorting (FACS) and perform RNA-seq on enriched populations. The processed data deposited here are also accessible in a graphical manner from a blast-based web interface available at https://hydratlas.unige.ch

overall_design:
Three or four replicates per sample, variable number of days of starvation.
>> Grant Information <<
Awarded to Dr. Brigitte Galliot:
- Swiss National Science Foundation (SNF grant 31003A-130337,
31003A_149630 & 31003_169930)
- NCCR Frontiers in Genetics, Stem Cells & Regeneration project
- The Canton of Geneva
- The Claraz donation
- Human Frontier Science Program (HFSP RHP0016-2010)


title: An evolutionary conserved Sp5-Wnt3 regulatory module contributes to restrict head organizer activity in Hydra

first: Leonardo

last: Beccari

address: 30 Quai Ernest Ansermet

summary: Head regeneration in Hydra requires the transformation of gastric tissue into a head organizer that produces a head activator and a head inhibitor. Here we report the decipherment of a long-standing question in developmental biology, the identification of the transcription factor Sp5 as a key head inhibitory component. We show that Sp5 has an apical to basal graded expression pattern in intact Hydra, its expression is induced upon Wnt/β-catenin signaling activation and when knocked-down triggers the formation of multiple heads and axes in homeostatic and regenerative conditions. Our data indicate that Sp5 acts in a feed-forward loop to robustly regulate its own expression and that Sp5 prevents head formation by repressing the Wnt3 promoter. This Sp5 mediated Wnt antagonism is conserved and was invented early in metazoan evolution to set up axial patterning.

overall_design: ChIP seq analysis of Sp5 occupancies in human HEK293 cells transfected with expression vectors coding either for Hydra Sp5 or Zebrafish Sp5 proteins.The genomic occupancies mutant versions of these proteins lacking the Sp5 DNA binding domain were also tested.

first: M

last: Vogg

first: L


title: The calcineurin splicing variant CnAb1 reduces pressure overload-induced cardiac hypertrophy by promoting mitohormesis

city: Madrid

first: Jesus

middle: Maria

last: Gómez-Salnero

address: Melchor Fernández Almagro, 3

country: Spain

institute: CNIC

summary:
Analysis of the function of CnAb1 in myocardial hypertrophy in mice using a Gain of Function strategy and Trans Aortic Banding as a hypertrophic stimuly.
Microarray was performed after QPCR validation of the upregulation of CnAb1.

overall_design: WT and CnAb1 transgenic overexpressing mice were subjected to a trans aortic banding and compared between them and a control group (sham).

first: Enrique

last: Lara-Pezzi


title: CD54+BP1+YFP- bone marrow stromal cells from IL7 reporter mice

first: Stéphane

last: Mancini

address: 27 Boulevard Lei Roure

summary:
Hematopoiesis in adult mammals involves cognate interactions between developing hematopoietic cells and bone marrow stromal cell niches. SCF and CXCL12 play key roles in the maintenance of HSC, while early B cell differentiation requires CXCL12 and IL7.
In this study, we characterized mouse BM stromal cells expressing IL7 by performing a transcriptomic analysis. We found that SCF, CXCL12 and IL7 were co-expressed by a unique peri-sinusoidal stromal cell subset.

overall_design:
CD45-Lin-CD54+BP1+ and CD45-Lin-YFP+CD54+BP1+ cells were isolated by flow cytometry from the bone marrow of 6 to 12 wo C57Bl/6J and IL7-Cre/Rosa-eYFP mice respectively (1800 to 10000 cells). Total bone marrow cells from C57Bl/6 mice were used as a control. Total RNA was amplified using the NuGEN Ovation Pico WTA System V2 Kit. cDNA hybridization was performed on Affymetrix Mouse GE ST 1.0 microarrays.
CD45-Lin-CD54+BP1+YFP- cells were isolated by flow cytometry from the bone marrow of 6 to 12 wo IL7-Cre/Rosa-eYFP mice (2300 cells). Total RNA was amplified using the NuGEN Ovation Pico WTA System V2 Kit. cDNA hybridization was performed on Affymetrix Mouse GE ST 1.0 microarrays.


title: PRC2 proteins EZH1 and EZH2 regulate postnatal hepatic maturation [srHC-seq]

first: Jessica

state: PA

overall_design: srHC-seq.  Long and small DNA fragments from sonicated, crosslinked chromatin were size-selected with AMPure XP beads and prepped for sequencing. Examination of a time-course including P14 and M2 hepatocytes using WT mice and P14 was also assessed for Ezh1/2 knockout mice. Five replicates per condition, with a mix of males and females.

first: Dario

last: Nicetto

first: Greg

last: Donahue

first: Kenneth

last: Zaret


title: Identifying circadian transcripts in human subcutaneous adipose tissue

city: Guildford

first: Jonathan

last: Johnston

address: Stag Hill campus

institute: University of Surrey

summary: The circadian system regulates many biological processes, including the transcriptome. An issue with human research is that serial sampling of tissues is difficult, and thus a temporal profile of the transcriptome is hard to generate. Using a technique developed at Surrey, biopsies of subcutaneous adipose tissue could be taken over multiple time points in one individual under highly controlled laboratory conditions. This study aimed to discover if the transcriptome of human subcutaneous adipose tissue was under circadian regulation, and whether key metabolic processes were under circadian variation.

overall_design: For each participant, 5 subcutaneous adipose tissue biopsies were taken at 6-hourly intervals. Biopsies were taken under the highly controlled conditions of a constant routine, used in the field of chronobiology. Each participant had followed a strict sleep/wake and meal schedule prior to the biopsies.

first: Skevoulla

last: Christou

first: Sophie

middle: T

last: Wehrens

first: Cheryl

last: Isherwood

first: Carla

last: Möller-Levet

first: Giselda

last: Bucca

first: Debra

last: Skene

first: Simon

last: Archer

middle: D


title: Expression array of stromal Mmp14-targeted mammary glands

first: Stephen

middle: J.

last: Weiss

state: MI

address: 210 Washtenaw Avenue

department: Life Sciences Institute

summary: Mammary gland branching morphogenesis is thought to depend on the mobilization of proteolytic machinery from the matrix metalloproteinase (MMP) family, namely MT1-MMP/MMP14, to drive coordinated epithelial cell invasion through the interstitial extracellular matrix, but the dominant effector has remained undefined. Unexpectedly, we find MMP14 controls postnatal mammary gland branching from the periductal stroma. Transcriptome profiling of stromal cell-targeted mammary glands was used to characterize the impact of stromal Mmp14-targeting on the growth factor and signaling cascades implicated in mammary gland morphogenesis. Transcriptome profiling of ductal networks and associated stroma was used to investigate the functional roles of MMP14 in the postnatal mammary gland stroma in an unbiased fashion.

overall_design: Intact mammary gland tissue was harvested from stromal cell-targeted conditional knockouts and wild-type littermates on a congenic C57BL/6J background at 4 weeks after birth for RNA extraction and hybridization on Affymetrix microarrays.

first: Tamar

middle: Y

last: Feinberg

middle: J


title: Transcriptomic analysis of mouse BM stromal cells expressing IL7

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


title: Parasite secreted products modulate STAT6-dependent and -independent transcription in macrophages

first: daniel

last: beiting

address: 380 S. University Ave

department: Pathobiology

summary: Toxoplasma gondii is an obligate intracellular protozoan parasite which, upon invasion of host cells, injects virulence factors that are known to induce dramatic alterations in host cell signaling.  Although much work has been directed at understanding the impact of specific secreted proteins on host cell function, dissecting the host response to injected virulence factors has been complicated by the fact that injection is rapidly followed by invasion, establishment of a parasitophorous vacuole in the host cell cytoplasm, secretion of parasite proteins from other specialized organelles, and remodeling of the host cell cytoskeleton  Here, we describe the global macrophage transcriptional response to secreted proteins and show that injection of rhoptry contents alone is sufficient to trigger a dramatic host cells response.  We further define modules of genes that are regulated in a parasite strain-specific manner by activation of the host transcription factor, STAT6.  Our approach leverages transgenic parasites that express mCherry and inject Cre-recombinase along with normal virulence factors into the cytoplasm of host cells.  Primary macrophages were recovered from transgenic reporter mice (Ai6) that express the ZsGreen1 fluorochrome when exposed to cre recombinase, allowing for the identification of a unique population of cells into which T. gondii injects virulence factors but does not infect (uninfected-injected, or U-I).  Transcriptional profiling of these U-I cells compared to infected cells or uninfected controls from the same cultures was carried out, using bone marrow derived macrophages (BMDM) from either WT or STAT6-/- mice. This data allows us to interrogate the outcomes T. gondii induced STAT signaling in both infected and U-I cell populations, and to resolve effects of injected virulence factors, like ROP16, from those changes induced by infection.

first: Daniel

last: Beiting

first: Christopher

last: Hunter

first: David

last: Christian

first: Lucas

last: Dawson

first: Jung

last: Oh


title: CD54+CD31-BP1+ and CD54-CD31+ bone marrow cells from wild type mice

first: Stéphane

last: Mancini

overall_design: CD45-Lin-CD54+CD31-BP1+ and CD45-Lin-CD54-CD31+ cells were isolated by flow cytometry from the bone marrow of 6 to 12 wo C57Bl/6J mice (1800 to 10000 cells). Total RNA was amplified using the Ambion MessageAmp II aRNA amplification kit. cDNA hybridization was performed on Affymetrix Mouse GE 430 2.0 microarrays.


title: CD8+ T cell response in the Act-mOVA/OT-I model of acute graft versus host disease

city: Budapest

first: Nikolett

last: Lupsa

state: Pest

address: Nagyvárad tér 4

department: Genetics, Cell-and Immunbiology

country: Hungary

institute: Semmelweis University

summary: Lethally irradiated C57Bl/6 Act-mOVA mice receiving allogeneic hematopoietic stem cell transplantation (aHSCT) from C57Bl/6  OT-I animals develop acute graft versus host disease (aGvHD) in a CD8+ T cell-dependent, reproducible manner, and succumb to the disease within 4-7 days. Tracking of UBC-GFP/OT-I graft CD8+ T cells discloses heavy infiltration of the GI tract, liver and lungs at the onset of the disease, and hallmark histologic features of acute gastrointestinal and hepatic GvHD, and aGVHD-associated lymphocytic bronchitis. This dataset describes gene expression patterns of CD45.1/OT-1 CD8+ T cells retrieved from the graft before (aHSCT + Day 0), and from various target organs of the host after (aHSCT + Day 4) grafting them into Act-mOVA recipients.

overall_design: Lethal acute graft versus host disease was induced in healthy 8-16 weeks old C57Bl/6 m-act OVA female mice by aHSCT. Recipient Act-mOVA mice received total body irradiation (11Gy, two split doses) and were transplanted with 3x10E+6 allogeneic bone marrow cells and 1,5x10E+7 splenocytes obtained from 8-16 weeks old C57Bl/6  OT-I mice serving as donors. Graft OT-I CD8+ T cells were obtained from CD45.1 animals, while all other graft cells and recipients carried the CD45.2 allele. For microarray experiments, on the day of transplantation, grafted naive CD45.1 CD8+ OT-I T cells were collected from the graft, serving as controls, by magnetic beads carrying CD45.1 specific antibodies. Four days after aHSCT, grafted CD45.1 CD8+ OT-I T cells were also recovered from the dissociated tissue samples of the livers, lungs and small intestines of Act-mOVA mice displaying acute GVHD by the same approach, and further analyzed by whole genome gene expression profiling.

first: Barbara

last: Ersek

first: Peter

last: Pocza

first: Anett

last: Toth

first: Andor

last: Horvath

first: Bence

last: Bagita

first: Andras

last: Bencsik

first: Hargita

last: Hegyesi

last: Matolcsy

first: Edit

last: Buzas

first: Zoltan

last: Pos


title: A new AdpA-dependent gene, required for morphological differentiation, in Streptomyces griseus.

city: Bunkyo-ku, Tokyo

first: Yasuo

last: Ohnishi

department: Department of Biotechnology

institute: Graduate School of Agriculture and Life Science, The University of Tokyo

summary: To identify genes affected by atuA mutation in solid culture, transcriptome profiles between wild-type and delta atuA mutant strains were analyzed.

overall_design: Analysis used wild-type strain RNA as control samples for comparison to the delta atuA mutant strain.

first: Akiyoshi

last: Higo


title: Induction Spodoptera midgut after induction by benzoxazinoids

city: Sophia Antipolis cedex

first: frederique

last: hilliou

address: 400 route des chappes, BP167

department: SPE

institute: INRA

summary:
L6 larvae midgut expression after induction by either DIBOA or DIMBOA
treatment1: DIBOA (13.5mM) versus DMSO (control)
treatment2: DIMBOA (13.5mM) versus DMSO (control)
DIBOA (2,4-Dihydroxy-1,4-benzoxazin-3-one glucoside) and DIMBOA (2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one) are benzoxazinoids compounds

overall_design:
DIBOA (2,4-Dihydroxy-1,4-benzoxazin-3-one glucoside) and DIMBOA (2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one) are benzoxazinoids compounds

tissue: midgut of L6 larvae of spodoptera frugiperda after 24h of feeding on artificial diet supplemented with benzoxazinoids.
3 biological replicates with Cy3-Cy5 dye swap .
treatment1: DIBOA (13.5mM) versus DMSO (control): total of 6 samples
treatment2: DIMBOA (13.5mM) versus DMSO (control): total of 6 samples

DIBOA experiment consists in 6 microarrays:
M1: DIBOArep1cy3 + DMSOrep1cy5
M2: DMSOrep1cy3 + DIBOArep1cy5
M3: DIBOArep2cy3 + DMSOrep2cy5
M4: DMSOrep2cy3 + DIBOArep2cy5
M5: DIBOArep3cy3 + DMSOrep3cy5
M6: DMSOrep3cy3 + DIBOArep3cy5
DIMBOA experiment consists in 6 microarrays:
M1: DIMBOArep1cy3 + DMSOrep1cy5
M2: DMSOrep1cy3 + DIMBOArep1cy5
M3: DIMBOArep2cy3 + DMSOrep2cy5
M4: DMSOrep2cy3 + DIMBOArep2cy5
M5: DIMBOArep3cy3 + DMSOrep3cy5
M6: DMSOrep3cy3 + DIMBOArep3cy5

first: Frederique

last: Hilliou

first: Pascal

last: Barbry

first: Kevin

last: Lebrigand


title: Gene expression changes in tumor following ADH-503 treatment

status: Public on Feb 28 2019

city: Saint Louis

first: Roheena

last: Panni

address: 660S Euclid Ave, Campus box 8109

institute: Washington University in Saint Louis

summary: To understand the effect of ADH-503, we have employed microarray expression profiling to identify genes that change at different times 48hrs and 10 days after treatment initiation.   CD11b/18 (alphaMbeta2), an integrin molecule is highly expressed on all myeloid cells and plays an important role in transendothelial migration and functional changes in these cells. Here we demonstrate that a small molecule agonist of CD11b, ADH-503 was associated reprograming tumor immunity by promoting anti-tumor immune cell populations by enhancing antigen presentation by macrophages and cDCs and together these changes resulted in stabilization of tumor growth and improvement in overall survival.

overall_design:
To understand the effect of ADH-503, we have employed microarray expression profiling to identify genes that change at different times after treatment initiation.
Treatment induced changes in gene expression at 48hrs and 10days after therapy in orthotopic pancreatic cancer model.

first: David

last: DeNardo


title: A novel Menin-MLL inhibitor induces specific chromatin changes and eradicates disease in models of MLL-rearranged leukemia

city: Sydney

first: Dominik

last: Beck

state: NSW

address: Level 10, UTS Building 11 (CB11 81-113, Broadway, Ultimo)

department: School of Biomedical Engineering

institute: University of Technology Sydney

summary:
Inhibition of the Menin (encoded by MEN1) and MLL1 (KMT2A) protein-protein interaction has been proposed as a potential targeted therapeutic strategy for MLL-rearranged (MLL-r) leukemia. We sought to develop more potent and selective Menin-MLL1 interaction inhibitors that are effective in vitro and in vivo to directly assess potential therapeutic opportunities. Structure-based design yielded the potent, highly selective and orally-bioavailable small molecule inhibitor VTP-50469. Human cell lines carrying MLL-rearrangements were highly sensitive and selectively responsive to treatment with VTP-50469. VTP-50469 displaced Menin from high molecular weight protein complexes and inhibited chromatin occupancy of MLL1 at select target genes. Loss of MLL1 binding led to specific changes in gene expression, cellular differentiation, and apoptosis. Mice engrafted with leukemia cells isolated from patients with either MLL-r AML or MLL-r ALL showed dramatic reductions of leukemia burden and prolonged survival when treated with VTP-50469. Remarkably, multiple mice engrafted with MLL-r ALL remained disease free greater than 1 year following cessation of treatment. Therefore, inhibition of the Menin-MLL1 interaction with VTP-50469 is highly effective in patient-derived xenograft (PDX) models of human MLL-r AML and MLL-r ALL which supports rapid translation of this approach to clinical trials.
This submission represents the scRNAseq component of the study.

overall_design: Single cell sequencing of full-length transcripts (scRNA-seq) was used to investigate molecular profiles of ALL PDX cells in response to VTP-50469 treatments for 28 days.

first: Duohui

last: Jing

first: Richard

last: Lock

first: Diego

last: Chacon


title: Differently expressed gene analysis in HeLa cells expressing high levels of phosphorylated PCNA

city: Beijing

first: bo

last: peng

address: Zhongguanchun street

department: School of Medicine

institute: Tsinghua University

summary: Cells expressing phosphorylation-mimicking PCNA, PCNA-Y211D, show elevated hallmarks specific to the epithelial-mesenchymal transition (EMT), including the upregulation of EMT-promoting factor Snail and the downregulation of EMT-inhibitory factors E-cadherin and GSK3β. These cells exhibit active cell migration and also undergo G2/M arrest. Interestingly, all of these EMT-associated activities require the activation of ATM and Akt, as inactivating these protein kinases by gene knockdown or inhibitors blocks EMT-associated signaling and cell migration. We conclude that PCNA phosphorylation promotes cancer progression via the ATM/Akt/GSK3β/Snail signaling pathway. This study, therefore, identifies a novel PCNA function and provides the molecular basis of phosphorylated PCNA-mediated cancer development and progression.

overall_design: mRNA profiles PCNA phosphorylation mimic and non-phosphorylation mimic HeLa knock-in cells were generated by deep sequencing on an Illumina platform.

first: Bo

last: Peng

first: Janice

last: Ortega

first: Liya

last: Gu

first: Zhijie

last: Chang

first: Guo-Min

last: Li


title: Verification and rectification of cell type-specific splicing of a Seckel syndrome-associated ATR mutation using iPS cell model

city: Kyoto

first: Jose

last: Ichisima

state: Kyoto

address: 53, Shogoin-Kawahara cho, Sakyo

department: Clinical Application Research

institute: Center for iPS cell research and application (CiRA), Kyoto University

summary: Seckel syndrome (SS) is a rare spectrum of congenital severe microcephaly and dwarfism. One SS-causative gene is Ataxia Telangiectasia and Rad3-Related Protein (ATR), and ATR (c.2101 A>G) mutation causes skipping of exon 9, resulting in a hypomorphic ATR defect in patients. Because ATR governs DNA repair response, the mutation has been considered the cause of an impaired response to DNA replication stress in neuronal progenitor cells (NPCs), which is associated with the pathogenesis of microcephaly. However, the precise mechanism through which the mutation causes SS remains unclear. To address this issue, we established induced pluripotent stem cells (iPSCs) from fibroblasts carrying the ATR mutation and an isogenic ATR-corrected counterpart iPSC clone by genome editing. Interestingly, SS-patient-derived iPSCs (SS-iPSCs) exhibited cell type-specific splicing; exon 9 was dominantly skipped in fibroblasts and iPSC-derived NPCs, but it was included in undifferentiated iPSCs and definitive endodermal cells. SS-iPSC-derived NPCs (SS-NPCs) showed distinct expression profiles from ATR non-mutated NPCs. In SS-NPCs, abnormal mitotic spindles were observed more frequently than in gene-corrected counterparts, and the alignment of NPCs in the surface of the neurospheres was perturbed. Finally, we tested several splicing-modifying compounds and found that a CLK1 inhibitor, TG003, could pharmacologically rescue the exon 9 skipping in SS-NPCs. Furthermore, treatment with TG003 restored the function of ATR in SS-NPCs and decreased the frequency of abnormal mitotic events. In conclusion, our iPSC model of SS revealed a novel function of the ATR mutation in NPCs and NPC-specific missplicing, proving its usefulness for dissecting the pathophysiology of ATR-SS.

overall_design: RNA-sequencing was conducted to identify the transcriptomic profiling of iPSC-derived cells

first: Megumu

last: Saito


title: Targeting Transcriptional Addiction by a Novel Highly Selective CDK9 Kinase Inhibitor for AML.

city: Hefei

first: Li

last: Wang

state: Anhui

address: Shushanhu road#350, building#2,Room 413

institute: High Magnetic Field Laboratory, Chinese Academy of Sciences (CHMFL)

summary: we reported a novel CDK9 high selective inhibitor JSH-009, it displayed high potency against CDK9 (IC50=1nM) and achieved high selectivity over CDKs family kinases (range from 200-10000 fold). JSH-009 showed high potent anti-proliferation effect in a range of AML cells and primary patient cells through downregulation of a number of transcriptional, apoptotic genes and related signaling pathways. In addition, this compound exhibited great anti-leukemic efficacy in the MV4-11 mediated xenograft, engraftment and AML PDX preclinical models. Currently, JSH-009 is under extensive preclinical development and We believe the work presented here would be of great interest to readers of Leukemia.

overall_design: AML cell HL60's mRNA profiles of  JSH-009 treatment and DMSO treatment were generated by deep sequencing, in two replicates, using Illumina HiSeq2000.

first: Chen

last: Hu

first: Aoli


title: Mice VSMCs: Control vs. TNF-α cultured

city: hunan

first: Rongrong

last: Cui

address: 139，renming road

institute: The second Xiangya hospital of central south university

summary:
Transcriptional profiling of mouse VSMCs comparing control  with VSMCs cultured with TNF-α
Apoptosis of vascular smooth muscle cells (VSMCs) is a process that regulates vessel remodeling in various cardiovascular diseases. The specific mechanisms that control VSMC apoptosis remain unclear. The present study aimed to investigate whether microRNA-494 (miR-494) is involved in regulating VSMC apoptosis and its underlying mechanisms. Cell death ELISA and terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling assays were used to detect apoptosis of murine VSMCs following stimulation with tumor necrosis factor(TNF-α). The results indicated that TNF-α-upregulated VSMC apoptosis in a dose-dependent manner. Microarray analysis was used to evaluate the expression profile of microRNAs following TNF-α-stimulation in murine VSMCs. The expression of miR-494 was downregulated, whereas B-cell lymphoma 2-like 11 (BCL2L11) protein expression levels were upregulated in VSMCs following treatment with TNF-  . Luciferase reporter assays confirmed that BCL2L11 was a direct target of miR-494. Transfection with miR-494 mimics decreased VSMC apoptosis and downregulated BCL2L11 protein levels. Conversely, transfection with miR-494 inhibitors increased cell apoptosis and upregulated BCL2L11 protein levels, suggesting that miR-494 may function as an essential regulator of BCL2L11. The increase in apoptosis caused by miR-494 inhibitors was abolished in cells co-transfected with BCL2L11-targeting small interfering RNA. The findings of the present study revealed that miR-494 inhibited TNF-α-induced VSMC apoptosis by downregulating the expression of BCL2L11.

overall_design: Two-condition experiment, Control vs.TNF-α cultured VSMCs . Biological replicates: 3 control, 3 TNF-α cultured VSMCs, independently grown and harvested.

first: Lu

last: Yi


title: Large-scale and high-confidence serum circulating miRNA biomarker discovery in prostate cancer

city: Kamakura

first: Ichikawa

last: Makiko

state: Kanagawa

institute: Toray Industries, Inc.

summary: A serum miRNA combination could be a powerful classifier for the detEsophageal Cancertion of patients with prostate cancer.

overall_design: Serum microRNA profiles of 1591 male samples, which consist of 809 of prostate cancers, 241 of negative prostate cancer patients, 41 of non-cancer controls, and 500 of the other solid cancers.

first: Fumihiko

last: Urabe

first: Juntaro

last: Matsuzaki

first: Yusuke

last: Yamamoto

first: Tomohiko

last: Hara

first: Takahiro

last: Kimura

first: Satoko

last: Takizawa

first: Yoshiaki

last: Aoki

first: Shumpei

last: Niida

first: Hiromi

last: Sakamoto

first: Ken

last: Kato

first: Shin

last: Egawa

first: Hiroyuki

last: Fujimoto

last: Ochiya


title: S frugiperda response to BX3 and BX1 maize mutant

first: frederique

last: hilliou

summary:
S. frugiperda fed with bx3 maize mutant and its control genotype B73 AND fed with bx1 maize mutant and its control genotype H88.

The bx1 mutant is derived from the insertion of a Mu element within the Bx1 gene in a H88 genetic background (Hamilton 1964). Similarly, the bx3 mutant was obtained in the genotype B73 by insertion of a Mu element in the Bx3 gene (Frey, Chomet et al. 1997).

overall_design:
The bx1 mutant is derived from the insertion of a Mu element within the Bx1 gene in a H88 genetic background (Hamilton 1964). Similarly, the bx3 mutant was obtained in the genotype B73 by insertion of a Mu element in the Bx3 gene (Frey, Chomet et al. 1997).
3 biological replicates with Cy3-cy5 dye swap
tissue: L6 larva midgut
treatment1: larvae feeding for 24h on 10-days-old bx3 plants and B73 control genotype. Total of 6 microarrays:
M1: bx3rep1cy3 + B73rep1cy5
M2: B73rep1cy3 + bx3rep1cy5
M3: bx3rep2cy3 + B73rep2cy5
M4: B73rep2cy3 + bx3rep2cy5
M5: bx3rep3cy3 + B73rep3cy5
M6: B73rep3cy3 + bx3rep3cy5
treatment2: larvae feeding for 24h on 10-days-old bx1 plants and H88 control genotype. Total of 6 microarrays:
M1: bx13rep1cy3 + H88rep1cy5
M2: H88rep1cy3 + bx1rep1cy5
M3: bx1rep2cy3 + H88rep2cy5
M4: H88rep2cy3 + bx1rep2cy5
M5: bx1rep3cy3 + H88rep3cy5
M6: H88rep3cy3 + bx1rep3cy5
normalization was done within array using loess method and  normalization between arrays using quantile method (limma package bioconductor). 'ratio' represents  test/reference

first: Pascal

last: Barbry

first: Kevin

last: Lebrigand


title: TNF-α induces IL-32 expression in HEK293 cells

first: Zhuqiang

last: Zhang

address: 15 Datun Road, Chaoyang District.

institute: Institute of Biophysics, CAS

summary: To see DNA methylation-repressed genes, we did RNA-seq in 5-aza treated cells and control cells. And we also did P65 ChIP-seq to see P65-dependent expressions.

overall_design: For RNA-seq, 5-aza treated cells and control cells were measured in two biological replicates; P65 ChIP-seq was done in ctrl cells and 12hr-TNF treated cells with one replicate respectively.

first: Zuodong

last: Zhao

first: Mengying

last: Lan

first: Jingjing

last: Li

first: Qiang

last: Dong

first: Xiang

first: Baodong

last: Liu

first: Gang

first: Hailin

last: Wang

first: Bing

last: Zhu


title: Epithelial endoplasmic reticulum stress orchestrates a protective IgA response I

city: Boston

first: Niklas

last: Krupka

state: MA

address: 77 Avenue Louis Pasteur

department: Medicine - Gastroenterology

institute: Brigham and Women's Hospital

summary: Immunoglobulin A (IgA) is the major secretory immunoglobulin isotype at mucosal surfaces where it regulates microbial commensalism and excludes luminal factors from contacting intestinal epithelial cells (IEC). IEC endoplasmic reticulum (ER) stress induces a polyreactive IgA response which protects from small intestinal inflammation. IEC ER stress causes expansion and activation of peritoneal B1b cells independent of microbiota and T cells that culminates in increased lamina propria and luminal IgA. Xbp1dIEC mice exhibit IEC ER stress by conditional deletion of X-box-binding protein 1 (XBP1). Here we examine differentially expressed genes in peritoneal B1b cells of germ-free Xbp1dIEC mice compared to littermate (WT) controls.

overall_design: Peritoneal B1b cell mRNA profiles of 10-week-old germ-free Xbp1dIEC or WT mice were generated by high throughput sequencing

first: Richard

last: Blumberg


title: Derivation of primodial germ cell-like cells from induced pluripotent stem cells of patients with idiopathic azoospermia

city: Wuhan

first: Zili

state: Hubei

institute: HuaZhong Science and Technology University

summary: At present, the etiology of most non-obstructive azoospermia (NOA) remains unclear, and the patients are diagnosed as idiopathic infertility. In vitro generation of patient-specific induced pluripotent stem cells (iPSCs) is an effective approach for exploring the mechanisms of human disease. Here, we established iPSCs from patients with idiopathic NOA, and differentiated them into human germline cells both in vitro and in vivo. Compared with normal hiPSCs, the idiopathic NOA patient-specific iPSCs show less efficiency of primodial germ cell-like cells (PGCLCs) formation in vitro and poor proliferation potential in vivo. Although the transcriptomes of PGCLCs are different from that of embryonic gonadal PGCs, the expression patterns of key genes involved in human PGC specification are generally similar during PGCLC induction process from all iPSCs lines, including the activation of BLIMP1, TFAP2C, NANOS3, SOX17, and T, and the repression of PRDM14 and SOX2. Moreover, the PGCLCs derived from idiopathic NOA patient-specific iPSCs initiate epigenetic reprogramming with repression of 5mC and presence of 5hmC. These findings provide a unique foundation for future mechanism research of male infertility.

overall_design: Transcriptome profiles of hiPSCs/hESCs, pre-induced iMeLCs, and EpCAM/INTEGRINα6 double positive PGCLCs were generated by RNA sequencing, in two replicates, by Illumina HiSeq2500.

first: Fang

last: Fang

first: Qian

first: Zhen

last: Ye

first: Yiting

last: Cai

first: Xiuli

last: Gu

first: Kai

first: Chunyan

first: Hui

last: Zhou

first: Tianqing

last: Meng

first: Zhe

last: Xiong

first: Shiliang

last: Shen

first: Honggang

first: Wenpei

last: Xiang

first: Chengliang