title: Translocation t(6;7) in AML-M4 cell line GDM-1 results in MNX1 activation through enhancer-hijacking [RNA-seq]

status: Public on Feb 28 2023

city: Heidelberg

first: Christoph

last: Plass

address: Im Neueneimer Feld 280

department: Division of Cancer Epigenomics

country: Germany

institute: DKFZ (German Cancer Research Center)

summary: The leukemic cell line GDM-1 was established from a patient with acute myelomonoblastic leukemia [4]. GDM-1 cells carry a reciprocal translocation t(6;7)(q23;q36) juxtaposing the transcription factor (TF) gene motor neuron and pancreas homeobox 1 (MNX1, also designated HLXB9 or HB9) on chromosome 7 (chr7) to the locus of the transcriptional activator MYB on chr6. The translocation does not result in a fusion transcript but leads to aberrant activation of MNX1, suspected to be due to altered topologically associating domains, nuclear positioning or ectopic mechanisms. GDM-1 represents the only AML cell line overexpressing MNX1. Here we demonstrate that the interaction between the MNX1 promoter with a ‘hijacked’ enhancer from the MYB/AHI1 locus leads to ectopic activation of MNX1.

overall_design: We performed mRNA sequencing for the AML cell line GDM-1.

first: Dieter

last: Weichenhan

first: Pavlo

last: Lutsik


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

status: Public on Mar 03 2023

city: Lebanon

first: Claudia

middle: V

last: Jakubzick

state: NH

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

department: Microbiology and Immunology

country: USA

institute: Dartmouth College

type: Expression profiling by high throughput sequencing

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

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

first: Xin

last: Li

first: Arlind

middle: B

last: Mara

first: Shawn

middle: C

last: Musial

first: Fred

middle: W

last: Kolling

first: Sophie

middle: T

last: Gibbings

first: Nikita

last: Gerebtsov


title: Translocation t(6;7) in AML-M4 cell line GDM-1 results in MNX1 activation through enhancer-hijacking [ACT-seq-BS]

type: Genome binding/occupancy profiling by high throughput sequencing

type: Methylation profiling by high throughput sequencing

overall_design: We performed Antibody-guided Chromatin Tagmentation bisulfite sequencing (ACT-seq-BS) for the AML cell line GDM-1, with antibodies for H3K27ac and H3K4me1.


title: Translocation t(6;7) in AML-M4 cell line GDM-1 results in MNX1 activation through enhancer-hijacking [ATAC-seq]

overall_design: We performed ATAC-seq in the AML cell line GDM-1.


title: Coordinated chemokine expression defines macrophage subsets across tissues

status: Public on Mar 02 2023

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

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

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Refer to individual Series

middle: L


title: Translocation t(6;7) in AML-M4 cell line GDM-1 results in MNX1 activation through enhancer-hijacking [ACT-seq]

overall_design: We performed Antibody-guided Chromatin Tagmentation sequencing (ACT-seq) in the AML-cell line GDM1, with antibodies against H3K27ac, H3K4me1, H3K4me3, MNX1 and IgG.


title: Translocation t(6;7) in AML-M4 cell line GDM-1 results in MNX1 activation through enhancer-hijacking [4C-seq]

overall_design: 4C-seq was performed for the AML cell line GDM-1 with 4 different viewpoints: MNX1, MYB, putative enhancer 1 in AH1 and exon 20 of AHI1.


title: The phenotype of the most common human ADAR1p150 Za domain mutation P193A in mice is incompletely penetrant

status: Public on Feb 13 2023

city: Meblourne

first: Alistair

middle: Morgan

last: Chalk

state: VIC

address: 1G Royal Parade

department: Bioinformatics

country: Australia

institute: WEHI

summary: ADAR1 mediated A-to-I RNA editing is a self/non-self discrimination mechanism for cellular double stranded RNAs. ADAR mutations are one cause of Aicardi-Goutières Syndrome, an inherited paediatric encephalopathy, classed as a “Type I interferonopathy”. The most common ADAR1 mutation is a proline 193 alanine (p.P193A) mutation, mapping to the ADAR1p150 isoform specific Za domain. We report the development of an independent murine P195A knock-in mouse, homologous to the human P193A mutation. The Adar1P195A/P195A mice are largely normal and the mutation is well tolerated. Contrasting with previous reports when the P195A mutation was compounded with an ADAR1 null allele (Adar1P195A/-), we find a partially penetrant phenotype, with approximately half the animals being runted with a shortened lifespan and the remaining animals normal. Severe runting and shortened survival of Adar1P195A/- animals were partly associated with the parental genotype. The P195A mutation is well tolerated in vivo and the loss of MDA5 is sufficient to completely rescue phenotypes in the Adar1P195A/- mice.

overall_design: Whole brain from 3-4 replicates of each genotype were subjected to RNA sequencing.

first: Zhen

last: Liang

middle: M

first: Scott

last: Taylor

first: Ankita

last: Gupte

first: Jacki

middle: E

last: Heraud-Farlow

first: Carl

middle: R

last: Walkley


title: Translocation t(6;7) in AML-M4 cell line GDM-1 results in MNX1 activation through enhancer-hijacking

status: Public on Feb 27 2023

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


title: Endothelial Differentiation of CCM1 Knockout iPSCs Triggers the Establishment of a Specific Gene Expression Signature

status: Public on Feb 23 2023

city: Hamburg

first: Matthias

last: Rath

address: Am Kaiserkai 1

department: Institute of Molecular Medicine

institute: MSH Medical School Hamburg

summary: We used RNA-seq to study the effect of CRISPR/Cas9-mediated CCM1 knockout in induced pluripotent stem cells (CCM1-/- iPSCs), iPSC-derived early mesoderm progenitor and endothelial-like cells (ePMCs and ECs).

overall_design: Comparative gene expression profiling analysis of RNA-seq data for wild-type and CCM1 knockout hiPSCs, early mesodermal progenitor cells and endothelial cells with 3 biological replicates each

first: Ute

last: Felbor

first: Robin

middle: A

last: Pilz

first: Dariush

last: Skowronek


title: A lysosomal surveillance response to stress extends healthspan [Exp1]

status: Public on Feb 03 2023

city: Lausanne

first: Terytty Yang

address: EPFL SV IBI-SV LISP AI 1145

country: Switzerland

institute: EPFL

summary: Lysosomes are cytoplasmic organelles central for the degradation of macromolecules to maintain cellular homeostasis and health. However, how lysosomal activity can be boosted to counteract aging and aging-related diseases remains elusive. Here, we reveal that silencing specific vacuolar H+-ATPase subunits (e.g. vha-6), that are essential for intestinal lumen acidification in Caenorhabditis elegans, extends lifespan by ~60%. This longevity phenotype can be explained by an adaptive transcriptional response typified by induction of a set of transcripts involved in lysosomal function and proteolysis, which we termed the lysosomal surveillance response (LySR). LySR activation is characterized by boosted lysosomal activity, enhanced clearance of protein aggregates in worm models of Alzheimer's disease, Huntington’s disease and amyotrophic lateral sclerosis, thereby improving fitness. The GATA transcription factor ELT-2 governs the LySR program and its associated beneficial effects. Activating the LySR pathway may therefore represent an attractive mechanism to reduce proteotoxicity and, as such, potentially extend healthspan.

overall_design: Wild-type C. elegans fed with control, vha-6, vha-16, and vha-19 RNAi

first: Terytty

middle: Y

first: Arwen

last: Gao

first: Xiaoxu

first: Johan

last: Auwerx


title: COVID-19 patient samples collected by the PREDICT-19 consortium

status: Public on Jan 30 2023

city: Darlington

first: Tracy

last: Chew

state: NSW

address: Merewether Building (H04) City Rd & Butlin Ave

department: Sydney Informatics Hub

institute: University of Sydney

summary: To investigate the role of gene expression in patients with COVID-19. Full article available at DOI: 10.1136/bmjopen-2020-044497.

overall_design: Comparative gene expression profiling analysis of patients wiith COVID-19 and control samples

first: Benjamin

last: Tang

first: Maryam

last: Shojaei


title: Epigenome-wide Association Study of Obesity Susceptibility in Human Twins

status: Public on Feb 18 2023

city: Pullman

first: Michael

middle: K

last: Skinner

state: WA

address: Abelson 507

department: SBS

institute: WSU

summary: The purpose of the current study was to use an epigenome-wide association approach (EWAS) to identify a potential DNA methylation alterations associated with obesity using twins discordant on obesity status. Buccal cells (from a cheek swab) were used as a purified marker cell for the epigenetic analysis. Analysis of differential DNA methylation regions (DMRs) was used to identify epigenetic associations with metabolic and dietary measures in obesity parameters discordant twins. An edgeR analysis provided a DMR signature with p<1e-04, but a false discovery rate analysis demonstrated a lack of significance due to low sample size and known multivariant origins of obesity.

overall_design:
The Washington State Twin Registry (WSTR) facilitated the collection and shipment of buccal cell samples from twins with and without obesity. Methylated DNA immunoprecipitation (MeDIP) was performed on the buccal cell DNA samples. The MeDIP was followed by DNA sequencing (MeDIP-Seq). Differential DNA methylation regions (DMRs) were identified for the male and female homozygous, heterozygous, and all twin pairs.
Please note that several samples do not have an associated processed data file. These samples were not used in the analyses prepared for publication due to QC or discordance issues. They are included in this submission for completeness.

first: Glen

last: Duncan

first: Ally

last: Avery

first: Millissia

last: Maamar

first: Eric

last: Nilsson

first: Daniel

last: Beck


title: Mutant NPM1 binds chromatin and directly regulates oncogenic transcription in acute myeloid leukemia

city: Boston

first: Scott

last: Armstrong

state: MA

address: 450 Brookline Ave

department: pediatric oncology

institute: Dana Farber Cancer Institute


title: A lysosomal surveillance response to stress extends healthspan [Exp2]

last: Li

overall_design: Wild-type C. elegans fed with control, vha-6, elt-2, or combination of vha-6 and elt-2 RNAi


title: Mutant NPM1 binds chromatin and directly regulates oncogenic transcription in acute myeloid leukemia [ChIP-seq]

summary: We use an endogenously degrader tagged NPM1c leukemia cell line that allows rapid small molecule induced degradation to show that NPM1c occupies specific chromatin targets in AML.

overall_design: To investigate the specificity and functional relevance of NPM1 mutant binding to chromatin, we used a previously described NPM1 mutant leukemia cell line (OCI-AML3-NPM1c-FKBP12) in which only the mutant allele of NPM1 is modified to produce an endogenously tagged version of NPM1c that has an FKBP12 ta.g

first: Hannah

last: Uckelmann

first: Charlie

last: Hatton


title: Multimodal epigenetic changes and altered NEUROD1 chromatin binding in the mouse hippocampus underlie FOXG1 syndrome

status: Public on Jan 09 2023

city: Freiburg

first: Tanja

last: Vogel

address: Albertstr. 23

institute: University of Freiburg

summary: The data presented in this study enlighten for the first time in a comprehensive manner diverse and multi-modal functions of FOXG1 at the chromatin level in mature neurons. Despite FOXG1 being recognized as a key transcription factor for telencephalic development and neuronal function, insights into the mechanism underlying transcriptional regulation are sparse. We here show that (i) FOXG1 acts both as repressor and activator, (ii) localizes predominantly to enhancer regions, (iii) alters the epigenetic landscape, (iv) affects directly HDAC functions, and (v) acts in concert with NEUROD1 to instruct transcriptional programs necessary for axono- and synaptogenesis.

overall_design: Bulk RNA-seq was performed in hippocampal tissue isolated from Foxg1cre/+ and Foxg1+/+ mice.

first: Stefanie

last: Heidrich

first: Thomas

last: Manke


title: Mutant NPM1 binds chromatin and directly regulates oncogenic transcription in acute myeloid leukemia [SLAM-seq]

overall_design: To investigate rapid changes just minutes after NPM1c degradation, we performed nascent mRNA sequencing (SLAM-seq) in NPM1 mutant leukemia cell line (OCI-AML3-NPM1c-FKBP12) in which only the mutant allele of NPM1 is modified to produce an endogenously tagged version of NPM1c that has an FKBP12 tag treated with dTAG-13 for 15 to 180 minutes.


summary: The integrative and multi-omics view of changes upon FOXG1 reduction reveals an unprecedented multimodality of FOXG1 functions converging on neuronal maturation, fueling novel therapeutic options based on epigenetic drugs to alleviate, at least in part, neuronal dysfunctions. This RNA-seq dataset is part of tis multimodal invetigation of FOXG1 functions.

overall_design: Cells were treated with shLuciferase (control) or shFoxg1 for the knockdown of expression of Foxg1, followed by either HDAC inhibitor TSA or control DMSO treatment. Bulk RNA-seq was performed in DIV11 hippocampal neurons from mice to investigate (i)the effect of Foxg1 KD on mature hippocampal neurons, (ii) interaction between FOXG1 and HDACs in transcriptional control.

first: Darren

last: O'Hailin

first: Francesco

last: Ferrari

first: Tudor

last: Rauleac

first: Ipek

last: Akol


title: Mutant NPM1 binds chromatin and directly regulates oncogenic transcription in acute myeloid leukemia [RNA-seq]

overall_design: To investigate the transcriptional changes after loss of NPM1c, we performed RNAseq using a previously described NPM1 mutant leukemia cell line (OCI-AML3-NPM1c-FKBP12) in which only the mutant allele of NPM1 is modified to produce an endogenously tagged version of NPM1c that has an FKBP12 tag


title: Mutant NPM1 binds chromatin and directly regulates oncogenic transcription in acute myeloid leukemia [PRO-seq]

overall_design: To investigate the changes in transcriptional activity and potential defects in initiation versus elongation of RNA polymerase II, we performed precisiojn run on sequenign (PRO-seq) in NPM1 mutant leukemia cell line (OCI-AML3-NPM1c-FKBP12) in which only the mutant allele of NPM1 is modified to produce an endogenously tagged version of NPM1c that has an FKBP12 tag. Treatment with dTAG-13 for 30 or 60 minutes was used to determine transcriptional changes after NPM1c degradation.


summary: We report that NEUROD1 mainly localises at distal intergenic and intronic regions in vitro, and colocalises with FOXG1.

overall_design: NEUROD1 ChIP-seq was performed on samples collected from DIV11 hippocampal neurons from E18.5 mice.


overall_design: RELACS ChIP-seq of H3K4me3 and H3K27ac were performed in DIV11 hippocampal neurons from E18.5 mice. Cells were treated with shLuciferase (control), and shFoxg1 for the knockdown of expression of FOXG1.

first: Chiara

last: Bella


title: Connecting ligand-induced retinoid X receptor structural dynamics to rexinoid agonist potency

status: Public on Jan 11 2023

city: New York

first: Laszlo

last: Halasz

state: NY

address: 1470 Madison Avenue

department: Department of Oncological Sciences

institute: Mount Sinai Icahn School of Medicine

summary: Retinoid X receptors (RXR) are nuclear transcription factors that partner with other nuclear receptors to regulate numerous physiological processes. Although RXR represents a valid therapeutic target, only a few RXR-specific ligands (rexinoids) have been identified, in part due to the lack of clarity on how rexinoids selectively modulate RXR response. Previously, we showed that rexinoid UAB30 potentiates all-trans-retinoic acid (ATRA) signaling in human keratinocytes by stimulating ATRA biosynthesis. Here, we examined the mechanism of action of next-generation rexinoids UAB110 and UAB111 that are more potent in vitro than UAB30 and the FDA-approved Targretin. Both UAB110 and UAB111 enhanced ATRA signaling in human organotypic epithelium at a 50-fold lower concentration than UAB30. This was consistent with the 2- to 5- fold greater increase in ATRA in skin rafts treated with UAB110/111 versus UAB30. Furthermore, at 0.2 µM, UAB110/111 increased the expression of ATRA genes up to 16-fold stronger than Targretin. The less toxic and more potent UAB110 also induced more changes in differential gene expression than Targretin. The hydrogen deuterium exchange mass spectrometry analysis showed that both ligands reduced the dynamics of the ligand-binding pocket but also induced unique dynamic responses that were indicative of higher affinity binding relative to UAB30, especially for Helix 3. UAB110 binding also showed increased dynamics towards the dimer interface through the Helix 8 and Helix 9 regions. These data suggest that UAB110 and UAB111 are potent activators of RAR: RXR signaling pathways but accomplish activation through different molecular responses to ligand binding.

overall_design: Trancriptomic profiling of human keratinocytes in response to rexinoid treatments (Veh, UAB30, UAB110 and Targretin), using high throughput sequencing (RNA-seq, triplicates, n=15).

first: Wilhelm

last: Berger

last: Nagy


overall_design: FOXG1 ChIP-seq was performed on hippocampal (CA+DG) samples collected from 6-week old wildtype mice.


overall_design: FOXG1 and NEUROD1 ChIP-seq was performed on samples collected from DIV11 hippocampal neurons treated with shFoxg1, shNeurod1 or shLuciferase.


title: A lysosomal surveillance response to stress extends healthspan

first: Terytty Yang

overall_design: Refer to individual Series


title: Immune-interacting lymphatic endothelial subtype at capillary terminals drives lymphatic malformation

status: Public on Jan 16 2023

city: Uppsala

first: Taija

last: Mäkinen

address: Dag Hammarskjölds v 20

department: Immunology, Genetics and Pathology, IGP

country: Sweden

institute: Uppsala University, Rudbeck Laboratory

summary: Oncogenic mutations in PIK3CA, encoding p110α-PI3K, are a common cause of venous and lymphatic malformations. Vessel type-specific disease pathogenesis is poorly understood, hampering development of efficient therapies. Here, we reveal a new immune-interacting subtype of Ptx3-positive dermal lymphatic capillary endothelial cells (iLECs) that recruit pro-lymphangiogenic macrophages to promote progressive lymphatic overgrowth. Mouse model of Pik3caH1047R-driven vascular malformations showed that proliferation was induced in both venous and lymphatic ECs, but sustained selectively in LECs of advanced lesions. Single-cell transcriptomics identified the iLEC population, residing at lymphatic capillary terminals of normal vasculature, that was expanded in Pik3caH1047R mice. Expression of pro-inflammatory genes, including monocyte/macrophage chemokine Ccl2, in Pik3caH1047R-iLECs was associated with recruitment of VEGF-C-producing macrophages. Macrophage depletion, CCL2 blockade or anti-inflammatory COX-2 inhibition limited Pik3caH1047R-driven lymphangiogenesis. Thus, targeting the paracrine crosstalk between iLECs and macrophages provides a new therapeutic opportunity for lymphatic malformations. Identification of iLECs further indicates that peripheral lymphatic vessels not only respond to but also actively orchestrate inflammatory processes.

overall_design: Dermal lymphatic endothelial cells (LECs) and blood endothelial cells (BECs) were FACS-sorted from the ear skin of 4-OHT-treated 5-week-old Pik3caH1047R;Cdh5-CreERT2 (n=5) and Cre- littermate control mice (n=2). One wild type C57BL/6J mouse, not treated with 4-OHT (n=1), was included.

first: Milena

last: Petkova

first: Marle

last: Kraft

first: Simon

last: Stritt

first: Ines

last: Martinez-Corral

first: Henrik

last: Ortsäter

first: Michael

last: Vanlandewijck

first: Bojana

last: Jakic

first: Eulalia

last: Baselga

first: Sandra

middle: D

last: Castillo

first: Mariona

last: Graupera

first: Christer

last: Betsholtz


first: Tanja

last: Vogel


summary: As part of our multimodal investigation fo FOXG1 functions at the chromatin, we report that there are both increase and decrease in chromatin accessibility upon reduced levels of FOXG1 in pirmary hippocampal neurons. The data presented in this study enlighten for the first time in a comprehensive manner diverse and multi-modal functions of FOXG1 at the chromatin level in mature neurons. Despite FOXG1 being recognized as a key transcription factor for telencephalic development and neuronal function, insights into the mechanism underlying transcriptional regulation are sparse. We here show that (i) FOXG1 acts both as repressor and activator, (ii) localizes predominantly to enhancer regions, (iii) alters the epigenetic landscape, (iv) affects directly HDAC functions, and (v) acts in concert with NEUROD1 to instruct transcriptional programs necessary for axono- and synaptogenesis.

overall_design: ATAC-seq was performed in DIV11 hippocampal neurons from E18.5 mice. Cells were treated with shLuciferase (control), and shFoxg1 for the knockdown of expression of FOXG1.

first: Darren

last: O'Hailin

first: Ipek

last: Akol

first: Thomas

last: Manke


title: DNA 5-methylcytosine regulates genome-wide formation of G-quadruplex structures [CUT&TAG]

status: Public on Dec 20 2022

city: Guangzhou

first: Lijun

last: Xiang

state: Guangdong

address: No.55, West of Zhongshan Avenue

department: Guangzhou Key Laboratory of Insect Development Regulation and Application Research

country: China

institute: South China Normal University

summary: G-quadruplex structures (G4s) have been identified in genomes of multiple organisms and proven to play important epigenetic regulatory roles in various cellular functions. However, the G4 formation mechanism remains largely unknown. Here, we found a negative correlation between DNA 5mC methylation and G4 abundance. The abundance of genomic G4s significantly increased when the whole-genome methylation level was reduced in DNMT1-knockout cells. This increase was then suppressed by DNMT1 over-expression. And more G4s were detected in the hypomethylated cancer cell line HepG2 and rectal cancer tissues. Besides, 5mC modification significantly inhibited G4 formation of the potential G-quadruplex sequences (PQSs). The transcription of genes with 5mC modification sites in their promoter PQSs was affected after treatment with G4 stabilizer pyridostatin or methylation inhibitor 5-aza-dC. The global reduction of genomic methylation elevates gene transcription levels through increased G4s. Taken together, DNA 5mC methylation prevents PQSs from folding into G4s in genomes.

overall_design: Anti-BG4 CUT&TAG in WT and DNMT1_KO HEK293T cells

first: Kangkang

last: Niu

first: Hui


title: DNA 5-methylcytosine regulates genome-wide formation of G-quadruplex structures [RNA-seq]

overall_design: Comparative gene expression profiling analysis of RNA-seq data for 293T cells and DNMT1-KO 293T cells


summary: We report that FOXG1 localises at promoter, distal intergenic and intronic regions in vitro.The data presented in this study enlighten for the first time in a comprehensive manner diverse and multi-modal functions of FOXG1 at the chromatin level in mature neurons. Despite FOXG1 being recognized as a key transcription factor for telencephalic development and neuronal function, insights into the mechanism underlying transcriptional regulation are sparse. We here show that (i) FOXG1 acts both as repressor and activator, (ii) localizes predominantly to enhancer regions, (iii) alters the epigenetic landscape, (iv) affects directly HDAC functions, and (v) acts in concert with NEUROD1 to instruct transcriptional programs necessary for axono- and synaptogenesis.

overall_design: FOXG1 ChIP-seq was performed on sampels collected from DIV11 hippocampal neurons from E18.5 mice.

first: Tudor

last: Rauleac

first: Stefanie

last: Heidrich


title: Aortic single-cell RNA sequencing in ACTA2 R179 variants

status: Public on Jan 01 2023

city: Stanford

first: Albert

middle: James

last: Pedroza

state: CALIFORNIA

address: 870 Quarry Rd, Falk CVRB

department: Cardiothoracic Surgery

institute: Stanford University

summary: Single-cell RNA datasets for aortic tissue from 8-week-old inducible smooth muscle cell-specific knock-in of Acta2 R179C mutation vs. littermate controls and aortic aneurysm tissue from a human patient carrying an ACTA2 R179H variant vs. a pediatric organ donor healthy control.

overall_design: Aortic tissue from 8-week-old control and smooth muscle cell-specific Acta2R179C knock-in mice was enzymatically digested and processed for single-cell RNA sequencing using 10X Genomics kit and pipeline. Separately, human aortic tissue was obtained from a young child with aortic aneurysm and ACTA2 R179H variant and discarded aortic tissue from a pediatric heart donor and similarly digested and processed.

middle: J

first: Callie

middle: S

last: Kwartler

first: Anita

last: Kaw

first: Dianna

last: Milewicz


title: SETD1A regulates transcriptional pause release of heme biosynthesis genes in leukemia [ChIP-Seq]

status: Public on Dec 09 2022

city: Chiba

first: Masaki

last: Fukuyo

address: 1-8-1 Inohana, Chuo-ku

department: Department of Molecular Oncology

country: Japan

institute: Chiba University

summary: Histone methyltransferase SETD1A is critical for acute myeloid leukemia (AML) cell survival, but the molecular mechanism driving SETD1A gene regulation remains elusive. To delineate the role of SETD1A, we utilize a protein degrader technology to induce rapid SETD1A degradation in AML cell lines. SETD1A degradation results in immediate downregulation of transcripts associated with DNA repair and heme biosynthesis pathways. CRISPR-based functional analyses and metabolomics revealed an essential role of SETD1A to maintain mitochondrial respiration in AML cells. These SETD1A targets are enriched in head-to-head (H2H) genes. SETD1A degradation disturbs a non-enzymatic SETD1A domain-dependent cyclin K function, increases the mono-Ser5P RNA polymerase II (RNAP2) at TSS, and induces the promoter-proximal pausing of RNAP2 in a strand-specific manner. This study reveals a non-enzymatic role for SETD1A in transcriptional pause release and provides insight into the mechanism of RNAP2 pausing and its function in cancer.

overall_design: 1) Examination of SETD1A targets in human MOLM-13 leukemia cell line, 2) Examination of histone modifications and RNAP2 modifications in SETD1A degraded MOLM-13 leukemia cell line. 3) Examination of elongation regulators in SETD1A degraded MOLM-13 leukemia cell line

first: Takayuki

last: Hoshii

first: Sarah

last: Perlee

first: Sota

last: Kikuchi

first: Bahityar

last: Rahmutulla

first: Takeshi

last: Masuda

first: Sumio

last: Ohtsuki

first: Tomoyoshi

last: Soga

first: Behnam

last: Nabet

first: Atsushi

last: Kaneda


title: Tight CDK1 inhibition elicits domain-specific pre-RC setting in S-phase, suppressing CFS instability

status: Public on Dec 31 2022

city: Paris

first: Chunlong

last: Chen

address: 26 rue d’Ulm

country: France

institute: Institut Curie

summary: Genome integrity requires replication to be completed before chromosome segregation. This coordination essentially relies on replication-dependent activation of a dedicated checkpoint that inhibits CDK1, delaying mitotic onset. Under-replication of Common Fragile Sites (CFSs), however, escapes surveillance, which generates mitotic chromosome breaks. Using human cells, we asked whether this leakage results from insufficient CDK1 inhibition under modest stresses used to destabilize CFSs. We found that tight CDK1 inhibition does suppress CFS instability in so-stressed cells. Molecular combing and Repli-Seq analyses consistently showed a burst of replication initiations in mid S-phase across large origin-poor domains shaped by transcription, including CFSs. CFS rescue and extra-initiations strikingly require availability of essential pre-Replication Complex (pre-RC) proteins during the S-phase, showing that CDK1 inhibition promotes targeted and mistimed pre-RC reloading. In addition to delay mitotic onset, tight checkpoint activation therefore advances replication completion of origin-poor domains at risk of under-replication, two complementary roles preserving genome stability.

overall_design: Repli-Seq experiments of human lymphoblastoid cells grown in the following conditions: Normal media (1 sample), 600 nM aphidicolin for 16h (1 sample), 600 nM aphidicolin and 10μM CDK1 inhibitor for 16h (two samples), 150μM HU for 16h (1 sample) and 150μM HU and 100mM Atr inhibitor for 16h.

first: Chun-Long

first: Stefano

last: Gnan

first: Olivier

last: Brison

first: Dana

last: Azar

first: Stéphane

last: Koundrioukoff

first: Mélanie

last: Schmidt

first: Rodrigo

last: Meledez-Garcia

first: Sami

last: El-Hilali

first: Yan

last: Jaszczyszyn

first: Anne-Marie

last: Lachages

first: Claude

last: Thermes

first: Michelle

last: Debatisse


title: DNA 5-methylcytosine regulates genome-wide formation of G-quadruplex structures

first: Lijun

last: Xiang

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


title: SETD1A regulates transcriptional pause release of heme biosynthesis genes in leukemia [RNA-seq]

first: Masaki

last: Fukuyo

first: Takayuki

last: Hoshii

first: Sarah

last: Perlee

first: Sota

last: Kikuchi

first: Bahityar

last: Rahmutulla

first: Takeshi

last: Masuda

first: Sumio

last: Ohtsuki

first: Tomoyoshi


title: The brain regulatory program predates central nervous system evolution

status: Public on Nov 22 2022

city: Bethlehem

first: Michael

middle: John

last: Layden

state: PA

address: 111 Research Dr

department: Biological Sciences

institute: Lehigh University

summary: Understanding how brains evolved is critical to determine the origin(s) of centralized nervous systems. Brains are patterned along their anteroposterior axis by stripes of gene expression that appear to be conserved, suggesting brains are homologous. However, the striped expression is also part of the deeply conserved anteroposterior axial program. An emerging hypothesis is that similarities in brain patterning are convergent, arising through the repeated co-option of axial programs. To resolve whether shared brain neurogenic programs likely reflect convergence or homology, we investigated the evolution of axial programs in neurogenesis. We show that the bilaterian anteroposterior program patterns the nerve net of the cnidarian Nematostella along the oral-aboral axis arguing that anteroposterior programs regionalized developing nervous systems in the cnidarian-bilaterian common ancestor prior to the emergence of brains. This finding rejects shared patterning as sufficient evidence to support brain homology and provides functional support for the plausibility that axial programs could be co-opted if nervous systems centralized in multiple lineages

overall_design: Single cell analysis of 24 hour post fertilization Nematostella vectensis gastrula with 4 technical replicates sequenced from the same original pool of isolated gastrula

first: Dylan

middle: Z

last: Faltine-Gonzalez

first: Jamie

last: Havrilak


title: Smurfness-based two-phase model of ageing helps deconvolve the ageing transcriptional signature [RNA-seq]

status: Public on Dec 03 2022

last: Rera

state: - None -

address: 8bis Rue Charles V, Center for Research and Interdisciplinarity

institute: UTELife lab

summary: Gene expression changes characterization in whole body Drosophila melanogaster mated females as a function of chronological age and Smurf status

overall_design: Comparative gene expression profiling analysis of RNA-seq data of Drosophila Drs-GFP line. Smurf and non-Smurf Individuals are sampled at three different time points (20 days – 90% survival, 30 days – 50% survival, 40 days – 10% survival), for a total of 32 samples (16 Smurfs and 16 non-Smurfs). Smurfs are sampled at a different time after transition (unknown time -Mixed samples, within 5 hours from transition – 5h, within 24h from transition -1d). In non – Smurfs, the “time after transition” indicates that the flies were sampled at the same moment of the corresponding Smurfs.  Comparisons are made to study the Smurf transcriptome and chronological age-related changes.

first: Flaminia

last: Zane

first: Hayet

last: Bouzid

first: Savandara

last: Besse

first: Sofia

last: Marmol

first: Julia

last: Molina

first: Céline

last: Cansell

first: Fanny

last: Aprahamian

first: Sylvere

last: Durand

first: Jessica

last: Ayache

first: Christophe

last: Antoniewski


title: SETD1A regulates transcriptional pause release of heme biosynthesis genes in leukemia

first: Masaki

last: Fukuyo


title: RNA-seq transcriptional profiling in  IL6 induced hepatocytes in vitro and livers after 2/3 partial hepatectomy

status: Public on Nov 19 2022

city: Shanghai

first: Meng

middle: meng

last: Jiang

address: number 3728, Jinke Road

institute: Shanghai Institute of Materia Medica

summary: We discover IL6, combined with EGF and HGF, promotes long-term expansion (>30 passages in ~150 days with theoretical expansion of ~1E+35 times) of primary mouse hepatocytes in vitro in simple 2D culture, by converting hepatocytes into induced hepatic progenitor cells (iHPCs), which maintain the capacity of differentiation into hepatocytes. IL6 also supports the establishment of single hepatocyte-derived iHPC clones. The summation of the downstream STAT3, ERK and AKT pathways induces a number of transcription factors which support the rapid growth.

overall_design: To further characterize IL6-iHPCs and IL6-iMHs, we compared their transcriptomic comparisonglobal gene expression to that of primary hepatocytes. To explore downstream transcription factors involved in IL6 induced hepatocytes proliferation, we evaluated the change of transcription factors in livers after PHX and during IL6 induced hepatocytes proliferation in vitro.

first: Xin

last: Xie

first: Ren

last: Guo

first: Mengmeng

first: Gang

last: Wang

first: Bing

last: Li


title: The Analysis of RNA-Sequencing Reveals the Immune Regulatory Roles of Key MiRNAs in Intestines of the Hybrid Yellow Catfish (Tachysurus fulvidraco♀ * P. vachellii♂) under transport stress

status: Public on Nov 13 2022

city: WuXi

first: Tao

last: Zheng

address: No.69, Xuejiali, Nanquan Town, Binhu District, Wuxi City, Jiangsu Province, China

institute: Wuxi Fisheries College, Nanjing Agricultural University

type: Non-coding RNA profiling by high throughput sequencing

summary: The miRNA negatively regulation of target genes expression indicated the immune role of integrating miRNA with mRNA targets may through TNF alpha-mediated pathways regulated immune response and intestinal injury under transport stress.

sample_organism: Tachysurus fulvidraco x Tachysurus vachelli

overall_design: we subjected to simulating the transport (0h, 2h, 4h, 8h, 16h) and setting recover 96h (after transport 16h), and intestinal biochemical and MiRNA-target gene analyses were performed in hybrid yellow catfish.

first: Jun

last: Qiang

first: Yifan

last: Tao

first: Siqi

last: Lu


title: Transgenerational Sperm DMRs and Low CpG Density Sites Escape Methylation Erasure in Embryonic Epigenetic Inheritance

status: Public on Nov 10 2022

first: Michael

last: Skinner

summary: Previous studies have suggested an erasure of DNA methylation is required to develop the stem cells in the morula embryo. An exception involves imprinted genes that escape this DNA methylation erasure. Transgenerational differential DNA methylation regions (DMRs) have been speculated to also escape this erasure. The current study was designed to assess if morula embryos escape erasure of DDT (dichloro-diphenyl-trichloroethane)-induced transgenerational sperm DMRs. Observations demonstrate that the transgenerational sperm DMR sites are not erased, so are imprinted-like DMR sites. Interestingly, we also found that the majority of low-density CpG genomic sites had a significant increase in DNA methylation in the morula embryo compared to sperm. The general erasure of DNA methylation during embryogenesis appears applicable for high-density CpG islands, but not low-density CpG deserts.

overall_design: The current study used intracytoplasmic sperm injection (ICSI) of control and DDT transgenerational (F3 generation) sperm to generate morula stage embryos for analysis of DNA methylation status of the DMRs. Sperm and morula samples were collected from both control and DDT exposure lineage rats. The DNA was extracted from the sperm and morula embryo pools. A methylated DNA immunoprecipitation followed by sequencing (MeDIP-seq) was performed on each of the control and DDT sperm and ICSI morula embryo pools.

first: Millissia

middle: B

last: Maamar

first: Yue

first: Eric

last: Nilsson

first: Daniel

last: Beck

first: Wei

last: Yan


title: Nanoparticle-mediated Targeting of the Fusion Gene RUNX1/ETO in  t(8;21)-positive Acute Myeloid Leukemia [CUT&RUN]

status: Public on Nov 09 2022

city: UTRECHT

first: Olaf

last: Heidenreich

state: UTRECHT

address: Prinses Máxima Centrum voor kinderoncologie | Postbus 113| 3720 AC BILTHOVEN | Heidelberglaan 25 |  3584CS UTRECHT | Nederland

country: Netherlands

summary:
To investigate the therapeutic potential of targeting RUNX1/ETO with lipid nanoparticles encapsulating chemically modefied siRNA.
Epegnomic profiling was performing on cells lines after lipid nanoparticles in vitro.

overall_design: Comparative epegnomic profiling of RUNX1/ETO, RUNX1 and CEBFB for Kasumi-1 and KSNO-1 cells from in vitro treatment with active siRNA against RUNX1/ETO (LNP/siRE-mod, KD) and control siRNA (LNP/siMM-mod, Ctrl).

first: Hasan

last: Issa

first: Minoo

last: Ashtiani


title: Nanoparticle-mediated Targeting of the Fusion Gene RUNX1/ETO in  t(8;21)-positive Acute Myeloid Leukemia [ATAC-seq]

institute: Prinses Máxima Centrum voor kinderoncologie

summary:
To investigate the therapeutic potential of targeting RUNX1/ETO with lipid nanoparticles encapsulating chemically modefied siRNA.
Chromatin Accessibility (ATAC-seq)  was performing on cells lines after lipid nanoparticles in vitro.

overall_design: Comparative chromatin accessibilty from in vitro treatment with active siRNA against RUNX1/ETO (LNP/siRE-mod) and control siRNA (LNP/siMM-mod).


title: Nanoparticle-mediated Targeting of the Fusion Gene RUNX1/ETO in  t(8;21)-positive Acute Myeloid Leukemia [RNA-seq]

summary:
To investigate the therapeutic potential of targeting RUNX1/ETO with lipid nanoparticles encapsulating chemically modefied siRNA.
Gene expression profiling was performing on cells lines after lipid nanoparticles in vitro and on harvested cells from treated mice in vivo.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for Kasumi-1 and KSNO-1 cells from in vitro treatment with active siRNA against RUNX1/ETO (LNP/siRE-mod) and control siRNA (LNP/siMM-mod). In vivo treatment of RG mice engrafted with Kasumi-1 cells and treated with active siRNA against RUNX1/ETO (LNP/siRE-mod) and control siRNA (LNP/siMM-mod)


title: Comparative analysis of single-cell and single-nucleus RNA-sequencing in a rabbit model of retinal detachment-related  proliferative vitreoretinopathy

status: Public on Nov 08 2022

city: Pittsburgh

first: Clayton

middle: Pio

last: Santiago

state: Pennsylvania

address: 1622 Locust Street

department: Ophthalmology

institute: University of Pittsburgh

summary: Proliferative vitreoretinopathy (PVR) is the most common cause of failure of retinal reattachment surgery and the molecular changes leading to this aberrant wound healing process is currently unknown. We aimed to study PVR pathogenesis using single-cell transcriptomics to dissect cellular heterogeneity in a rabbit PVR model. PVR was induced unilaterally in Dutch Belted rabbits. At different timepoints following PVR induction, retinas were dissociated into either cells or nuclei suspension and processed for single-cell or single-nucleus RNA sequencing (scRNA-seq or snRNA-seq). ScRNA-Seq and snRNA-Seq were conducted on retinas at 4 hours and 14 days after disease induction. While the capture rate of unique molecular identifiers (UMI) and genes were greater in scRNA-seq samples, overall gene expression profiles of individual cell types were highly correlated between scRNA-seq and snRNA-seq. A major disparity between the two sequencing modalities is the cell type capture rate, however, with glial cell types over-represented in scRNA-seq, and inner retinal neurons were enriched by snRNA-seq. Furthermore, fibrotic Müller glia were over-represented in snRNA-seq samples, while reactive Müller glia were in scRNA-seq samples. Trajectory analyses were similar between the two methods, allowing for the combined analysis of the scRNA-seq and snRNA-seq datasets.These findings highlight limitations of both scRNA-seq and snRNA-seq analysis and imply that use of both techniques can more accurately identify transcriptional networks critical for aberrant fibrogenesis in PVR.

overall_design: Retinas from control or PVR induced rabbits were dissociated into a single cell suspension or lysed into a single nuclei solution and run on the 10x Genomics Chromium Single Cell System platform using ver3.1 chemistry. Libraries were sequenced on Illumina NovaSeq 6000 and processed through the Cell Ranger pipeline using the OryCun2.0 reference genome.

middle: P

first: Megan

last: Gimmen

first: Yuchen

first: Minda

last: McNally

first: Leighton

middle: H

last: Duncan

first: Tyler

last: Creamer

first: Linda

last: Orzolek

first: Seth

last: Blackshaw

first: Mandeep

last: Singh


title: Nanoparticle-mediated Targeting of the Fusion Gene RUNX1/ETO in  t(8;21)-positive Acute Myeloid Leukemia

overall_design: Refer to individual Series


title: cAMP and mGluR1/5 dependent expression of mRNA, lncRNA, and miRNA in mouse hippocampal neurons

status: Public on Nov 07 2022

city: Jupiter

first: Sathyanarayanan

middle: V

last: Puthanveettil

state: Florida

address: 130 Scripps Way

department: Neuroscience

institute: Scripps Florida

summary: To identify cAMP-dependent and mGluR1/5-dependent RNAs, we treated DIV16 primary hippocampal neurons with 50uM Forskolin, 30uM DHPG, or equal volume DMSO for 30 minutes prior to RNA isolation using Trizol and Total/small RNA sequencing. We submitted samples to Scripps Florida Genomics Core for library preparation and sequencing.

overall_design: Hippocampi were cultured from P0 mice for generating RNA at DIV 16. We treated DIV16 primary hippocampal neurons with 50uM Forskolin, 30uM DHPG, or equal volume DMSO for 30 minutes.

first: Eddie

last: Grinman


title: Pre-assembled Cas9 ribonucleoprotein-mediated gene deletion identifies the carbon catabolite repressor and its target genes in Coprinopsis cinerea

status: Public on Nov 01 2022

city: Szeged

first: Botond

last: Hegedüs

state: Csongrád-Csanád

address: Temesvári krt. 62

department: Institute of Biochemistry

country: Hungary

institute: Biological Research Center

summary: Cre1 is an important transcription factor that regulates carbon catabolite repression (CCR) and is widely conserved across fungi. This gene has been extensively studied in several Ascomycota species, whereas its role in gene expression regulation in the Basidiomycota remains poorly understood. Here, we identified and investigated the role of cre1 in Coprinopsis cinerea, a basidiomycete model mushroom that can efficiently degrade lignocellulosic plant wastes. We used a rapid and efficient gene deletion approach based on PCR-amplified split-marker DNA cassettes together with in-vitro assembled Cas9-guide RNA ribonucleoproteins (Cas9-RNPs) to generate C. cinerea cre1 gene deletion strains. Gene expression profiling of two independent C. cinerea cre1 mutants showed significant deregulation of carbohydrate metabolism, plant cell wall degrading enzymes (PCWDEs), plasma membrane transporter-related and several transcription factor encoding genes, among others. Our results support the notion that, similarly to reports in the ascomycetes, Cre1 of C. cinerea orchestrates CCR through a combined regulation of diverse genes, including PCWDEs, transcription factors that positively regulate PCWDEs and membrane transporters which could import simple sugars that can induce the expression of PWCDEs. Somewhat paradoxically, though in accordance with other Agaricomycetes, genes related to lignin degradation were mostly downregulated in cre1 mutants, indicating they fall under different regulation than other PCWDEs. The gene deletion approach and the data presented in this paper expand our knowledge of CCR in the Basidiomycota and provide functional hypotheses on genes related to plant biomass degradation.

overall_design: Vegetative mycelium samples from wild type and cre mutant Coprinopsis cinerea strains growth on YMG (0.2% glucose) were collected and profiled. Each group has 2-3 replicates.

first: Manish

last: Pareek

first: Zhihao

last: Hou

first: Árpád

last: Csernetics

first: Hongli

last: Wu

first: Máté

last: Virágh

first: Neha

last: Sahu

first: Xiao-Bin

last: Liu

first: László

middle: G

last: Nagy


title: Single cell RNA-seq from primary ccRCC-patient-derived cell cultures on the 10X genomics platform

status: Public on Nov 15 2022

city: Oxford

first: David

middle: Robert

last: Mole

address: Roosevelt Drive, Headington

department: Nuffield Department of Medicine

country: United Kingdom

institute: University of Oxford

summary: HIF-metagene identifies hypoxic or constitutive HIF activation in scRNA-seq. Hypoxic normal cells have higher HIF-metagene scores than normoxic normal cells, and ccRCC tumour cells (harbouring VHL inactivation) have higher HIF-metagene score than normal cells.

overall_design:
Assess single cell HIF-metagene activation in primary cultures in hypoxic conditions and upon VHL inactivation

>>>Submitter states that raw data are not available due to patient privacy concerns<<<

first: Olivia

last: Lombardi

first: Ran

last: Li

middle: R


title: RNA-seq analysis of different parts of Quercus robur seedling root

status: Public on Nov 23 2022

city: Poznan

first: Michał

last: Szcześniak

address: Uniwersytetu Poznanskiego 6

department: Institute of Human Biology and Evolution

country: Poland

institute: Adam Mickiewicz University

summary: As an adaptive response to the environment, oaks have evolved long taproots that increase their ability to acquire water. Taproots penetrate deeper layers of soil and send out absorptive roots that can then uptake water from these layers. This ability enables taproots to supply trees with water better. Unfortunately, the applied agrotechnical procedures during seedlings production in container nurseries damage the oaks' taproot, leading to changes in the root system structure. That changes may make the seedlings more responsive to chronic or periodic episodes of severe drought. In turn, seedlings that containers do not restrict roots growth, i.e. grown in rhizotron, may elongate because they are not subjected to air-pruning. Despite their significant role, little is known about the internal factors (specific genes) and their interactions that regulate taproot elongation in oaks seedlings. Thus, our study aimed to determine the potential genes regulating growth, cessation and physiology of taproot and check whether there is a difference in the expression level of the genes involved in root development. For this purpose, we performed next-generation sequencing (NGS), taproots and lateral roots, which allowed us to obtain a complete picture of the transcriptomes. Our findings of taproot growth regulations can be used to improve trees production in forest nurseries.

overall_design: Identification of genes involved in the regulation of taproot growth in containerized oak seedlings and seedlings sown directly in the soil.

first: Paulina

last: Kościelniak

last: Glazińska

first: Marcin

last: Zadworny


title: Deleterious, protein-altering variants in the transcriptional coregulator ZMYM3 in 27 individuals with a neurodevelopmental delay phenotype

status: Public on Oct 31 2022

city: Huntsville

first: Chris

last: Partridge

state: AL

address: 601 Genome Way

institute: HudsonAlpha Institute

summary: Neurodevelopmental disorders (NDDs) result from highly penetrant variation in hundreds of different genes, some of which have not yet been identified. Using the MatchMaker Exchange, we assembled a cohort of 27 individuals with rare, protein-altering variation in the transcriptional coregulator gene ZMYM3, located on the X chromosome. Most (n=24) individuals were males, 17 of which have a maternally inherited variant and four of which have de novo variants. Overlapping features included developmental delay, intellectual disability, behavioral abnormalities, and a specific facial gestalt in a subset of males. Variants in almost all individuals (n=26) are missense, including six with variants that have arisen independently at the same codon at least two times. Four unrelated probands were identified with inherited variation at Arg441 (Arg441Trp or Arg441Gln), a site at which variation has been previously seen in NDD-affected siblings, and two individuals have de novo variation at Arg1294 (Arg1294Cys). All variants affect evolutionarily conserved sites, and most are predicted to damage protein structure or function. ZMYM3 is relatively intolerant to variation in the general population, is widely expressed across human tissues, and encodes a component of the KDM1A-RCOR1 chromatin-modifying complex. ChIP-seq experiments on one mutant, Arg1274Trp, indicate dramatically reduced genomic occupancy, supporting a hypomorphic effect. While we are unable to perform statistical evaluations to support a conclusive causative role for variation in ZMYM3 in disease, the totality of the evidence, including 27 affected individuals, recurrent variation affecting at least two codons, overlapping phenotypic features, protein-modeling data, evolutionary constraint, and experimentally-confirmed functional effects strongly support ZMYM3 as a novel NDD gene.

overall_design: HepG2 cells edited by CRISPR/Cas9 to add a FLAG epitope tag to ZMYM3; clinically-identified variant mutation edited into cells, with corresponding control; Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq)

first: Susan

middle: M

last: Hiatt

first: E

middle: C

first: Gregory

last: Cooper


title: Gene expression data from lsd1 mutant zebrafish embryos

status: Public on Nov 25 2022

city: Salt Lake City

first: Rodney

last: Stewart

state: UT

address: 2000 Circle of Hope Dr

department: Oncological Sciences

institute: University of Utah

summary: Gene expression of zebrafish lsd1 mutants and wildtype sibling tails were analyzed by RNA-seq.

overall_design: RNA-Seq performed on 6 zebrafish lsd1 mutant and 5 wildtype sibling tails pooled in groups of 5 tails each, in triplicate at 24hpf. The Illumina NovaSeq 150 x 150 bp Sequencing 100 M read-pairs sequencing protocol was used.

first: Mattie

last: Casey

first: Michael

middle: E

last: Engel

middle: A


title: Prior IL-4 exposure induces epigenetic reprograming enabling activated NF-kB p65 cistrome expansion, extreme synergistic gene activation and unique imuune response in macrophages

status: Public on Oct 20 2022

city: New York

first: Laszlo

last: Halasz

address: 1470 Madison Avenue

institute: Mount Sinai Icahn School of Medicine

summary: Prior exposure to certain signals can fundamentally change the response of innate immune cells to other stimuli underpinning phenomena such as cellular memory, tissue type-specific reactions, cytokine storm or anergy/tolerance. Our understanding about the molecular details of such interactions especially at the level of chromatin accessibility and gene expression regulation is fragmented.  In particular our knowledge about the molecular links between two fundamental signaling pathways, alternative macrophage polarization signals and TLR signaling pathway is rather limited and neither the epigenomic mechanisms at play nor the biological output is well understood. Here we combined systematic signaling, epigenomic and transcriptomic approaches to map and uncover that the activation of the IL-4-STAT6 signaling pathway results in enhanced LPS responsiveness of a large, but distinct set of genes in macrophages. This interaction, we termed extreme synergy, is brought about by IL-4 priming-induced STAT6-dependent epigenomic remodeling, which includes the expansion of the LPS-activated NFκB-p65 cistrome, increased chromatin accessibility, epigenomic activation and increased enhancer activity at the genomic loci of synergistically activated genes. The IL-4-induced EGR2 transcription factor is required to enable the LPS-induced de novo and enhanced NFκB-p65 binding and synergistic gene activation. As a consequence, the previously alternatively polarized macrophages produce secreted immune-modulatory factors, including CCL17, CCL22, CCL2, and EDN1, at an extremely high level in vitro and in vivo in a murine Th2-type airway inflammation and asthma model following LPS exposure. Our findings establish that the IL-4-STAT6-EGR2 signaling pathway-induced epigenetic reprogramming is responsible for the development of a defined, robust inflammatory hyperresponsiveness to TLR4 activation in alternatively polarized macrophages and likely contribute to pathologies.

overall_design: Transcriptomic and epigenetic profiling of IL-4-primed and LPS-activated bone-marrow derived macrophages (BMDMs), using high throughput sequencing (RNA-seq, ChIP-seq and ATAC-seq).

first: Zsolt

last: Czimmerer


title: Gas5 Pulldown Total and small RNAseq

first: Sathyanarayanan

last: Puthanveettil

summary: To identify RNAs interacting with lncRNA Gas5 in hippocampal neurons, we performed a Gas5 pulldown from mouse hippocampal cultures using a biotinylated Gas5 bait and performed total and small RNA sequencing

overall_design: Gas5 Pulldown

first: Eddie

last: Grinman


title: Hypermitotic meningiomas harbor DNA methylation subgroups with distinct biological and clinical features

status: Public on Oct 10 2022

city: San Francisco

first: William

last: Chen

state: CA

address: 1450 3rd Street, HD 402

institute: UCSF

summary: This study reports clinical, genetic, epigenetic, gene expression, and cellular features distinguishing meningioma DNA methylation subgroups within meningioma DNA methylation groups. We present these data in the context of molecular and clinical models predicting postoperative outcomes across 565 meningiomas with comprehensive clinical follow-up from independent discovery and validation institutions. By discovering meningioma DNA methylation subgroups within meningioma DNA methylation groups, we provide an opportunity to resolve inconsistencies in the recent literature. In doing so, our study establishes an architecture that unifies opposing biological theories for the most common primary intracranial tumor

overall_design: RNA-sequencing data is used to examine transcriptional signatures of meningioma subgroups in the context of methylation classification.

first: Abrar

last: Choudhury

first: David

last: Raleigh


title: The OncoLoop Network-based  Precision Oncology Framework

first: Juan

last: Arriaga

address: 1425 Madison Ave

department: Oncological Sciences, Urology

institute: Icahn School of Medicine at Mount Sinai

summary: We introduce OncoLoop, a highly-generalizable, precision medicine framework to triangulate between available mouse models, human tumors, and large-scale drug perturbational assays with in vivo validation to predict personalized treatment

overall_design: This series includes RNAseq from ten new and previously published genetically-engineered mouse models of prostate cancer. RNAseq from such primary tumors was used to construct a new interactome and to perform master regulator analysis that stratify individual tumors into molecular subtypes that are conserved with human prostate cancer tissues. By matching mouse models to patients and to drug reversion signatures, we validate that the OncoLoop algorithm predicts particular tumor vulnerabilities of individual tumors solely on transcriptome analysis.

first: Alessandro

last: Vasciaveo


title: A ribosomal protein homolog modulates gene expression and virulence in a bacterial pathogen

status: Public on Sep 09 2022

city: Kingston

first: Kathryn

last: Ramsey

state: RI

address: 7 Greenhouse Road

department: CMB / BPS

institute: University of Rhode Island

summary: To assess which F. tularensis LVS transcripts are impacted by loss of bS21-2, we generated cells lacking the gene encoding bS21-2 (LVS ∆rpsU2). We then grew wild-type cells containing an empty vector (LVS pF), cells lacking bS21-2 with empty vector (LVS ∆rpsU2 pF), and cells lacking the native bS21-2 but ectopically expressing bS21-2 from a plasmid (LVS ∆rpsU2 pF-rpsU2-V). We isolated RNA from mid-log phase cells and analyzed by RNA-Seq.

sample_organism: Francisella tularensis subsp. holarctica LVS

overall_design: Comparative gene expression profiling analysis of RNA-Seq data for wild-type F. tularensis LVS with empty vector (WT pF), cells lacking bS21-2 with empty vector (LVS ∆rpsU2 pF), and LVS ∆rpsU2 ectopically expressing bS21-2 (LVS ∆rpsU2 pF-rpsU2-V)

first: Hannah

last: Trautmann


title: JAG1-NOTCH4 mechanosensing drives atherosclerosis

status: Public on Sep 06 2022

city: London

first: Paul

last: Evans

address: Charterhouse square

institute: QMUL

summary: Endothelial cell (EC) sensing of fluid shear stress regulates atherosclerosis, a disease of arteries that causes heart attack and stroke. Atherosclerosis preferentially develops at regions of arteries exposed to low oscillatory shear stress (LOSS), whereas high shear regions are protected. We show using inducible EC-specific genetic deletion in hyperlipidaemic mice that the Notch ligands JAG1 and DLL4 have opposing roles in atherosclerosis. While endothelial Jag1 promoted atherosclerosis at sites of LOSS, endothelial Dll4 was atheroprotective. Analysis of porcine and murine arteries and cultured human coronary artery EC exposed to experimental flow revealed that JAG1 and its receptor NOTCH4 are strongly upregulated by LOSS. Functional studies in cultured cells and in mice with EC-specific deletion of Jag1 show that JAG1-NOTCH4 signalling drives vascular dysfunction by repressing endothelial repair. These data demonstrate a fundamental role for JAG1-NOTCH4 in sensing LOSS during disease, and suggest therapeutic targeting of this pathway to treat atherosclerosis.

overall_design: Samples are from 4 HCAEC donors and were used to prepare RNA-seq libraries that were sequenced on an Illumina HiSeq platform.

first: Celine

last: Souilhol

first: Xiuying

last: Li

first: Lindsay

last: Canham

last: Roddie

first: Daniela

last: Pirri

first: Blanca

middle: T

last: Ayllon

first: Emily

last: Chambers

first: Mark

middle: J

last: Dunning

last: Ariaans

first: Jin

first: Yun

last: Fang

first: Maria

last: Fragiadaki

first: Victoria

last: Ridger

first: Jovana

last: Serbanovic-Canic

first: Sarah

last: de Val

first: Sheila

last: Francis

first: Timothy

last: Chico


title: JAG1-NOTCH4 mechanosensing drives atherosclerosis [single-cell RNA-seq]

last: Evans

overall_design: Samples are from murine aorta in Jag1 knockout and control mice and used to create scrna-seq libraries.

first: Hannah

last: Tardajos Ayllon


title: RNAseq analysis of A549 and THP1 cells infected with H3N2 influenza A virus

status: Public on Aug 31 2022

city: Münster

first: Klaus

last: Schughart

address: Von-Esmarch-Str 56

department: Virology

institute: University Münster

summary:
Gene expression changes were studied by RNAseq
Results: Differentially expressed genes in different cell types and at different time points after infection

overall_design: A549 and THP1 cells were infected with H3N2 influenza A virus, RNA was prepared and sequenced

first: Ana

last: Eulalio

first: Carmen

last: Aguilar


title: Impact of sex on the colon transcriptome during AOM/DSS treatment

status: Public on Sep 28 2022

city: Solna

first: Cecilia

last: Williams

address: Tomtebodav 23

institute: Karolinska Institute

summary: In order to improve the understanding of the impact of sex during colorectal cancer development we sequenced, for the first time, the colonic epithelium of wild-type mice of both sexes treated with 9 or 15 weeks AOM/DSS.

overall_design: Colon mRNA profiles of female and male WT mice on a C57BL/6J background were generated by deep sequencing. 5 biological replicates were used.

first: Linnea

last: Pettersson

first: Amena

last: Archer


title: Analysis of differentially expressed circRNAs after EGFR-TKI treatment

status: Public on Aug 26 2022

city: Nanjing

first: Feng

last: Jiang

state: Jiangsu

address: Baiziting 42

institute: Jiangsu Institute of Cancer Research

summary: CircRNA-seq of H1975 cells treated with DMSO or Osi (500 nM) and PC9 cells treated with DMSO or Ge (100 nM) for 3 days

overall_design: H1975 cells were treated with DMSO or Osi, while PC9 cells were treated with DMSO or Ge for 3 days followed by circRNA-sequencing

first: Hui

last: Wang


title: Enteric Glial Cell Network Function is Required for Epithelial Barrier Restitution following Intestinal Ischemic Injury in the Early Postnatal Period

status: Public on Sep 08 2022

city: Raleigh

first: Amanda

middle: L

last: Ziegler

state: NC

address: 1060 William Moore Drive

department: Clinical Science

institute: NC State University

summary: Ischemic damage to the intestinal epithelial barrier, such as in necrotizing enterocolitis or small intestinal volvulus, is associated with higher mortality rates in younger patients. We have recently reported a powerful pig model to investigate these age-dependent outcomes in which mucosal barrier restitution is strikingly absent in neonates but can be rescued by direct application of homogenized mucosa from older, juvenile pigs by a yet-undefined mechanism. Within the mucosa, a postnatally developing network of enteric glial cells (EGC) is gaining recognition as a key regulator of the mucosal barrier. Therefore, we hypothesized that the developing EGC network may play an important role in coordinating intestinal barrier repair in neonates. Neonatal and juvenile jejunal mucosa recovering from surgically induced intestinal ischemia was visualized by scanning electron microscopy and the transcriptomic phenotypes were assessed by bulk RNA sequencing. EGC network development was examined by gene set enrichment analysis, three-dimensional volume imaging and western blot and its function in regulating epithelial restitution assessed ex vivo in Ussing chamber using the glia-specific inhibitor fluoroacetate, and in vivo in co-culture assays. Here we refine and elaborate our translational model, confirming a neonatal phenotype characterized by a complete lack of coordinated reparative signaling in the mucosal microenvironment. Further, we report important evidence that the subepithelial EGC network changes significantly over the early postnatal period and demonstrate that EGC function in close proximity to wounded intestinal epithelium is critical to intestinal barrier restitution following ischemic injury.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for homogenized mucosa of control and ischemia-injured jejunum of 2- and 6-week-old pigs.

first: Madison

last: Caldwell

first: Sara

last: Craig

first: Emily

last: Hellstrom

first: Anastasia

last: Sheridan

first: Melissa

middle: S

last: Touvron

first: Tiffany

last: Pridgen

first: Scott

last: Magness

first: Jack

last: Odle

first: Laurianne

last: Van Landeghem

first: Anthony

last: Blikslager


title: Quantitative sequencing using BID-seq uncovers abundant pseudouridines in mammalian mRNA at base resolution

status: Public on Sep 05 2022

city: Chicago

first: Li-Sheng

last: Zhang

state: IL

address: 929 E 57th St Rm E313

department: Department of Chemistry

institute: The University of Chicago

summary: Functional characterization of pseudouridine (Ψ) in mammalian messenger RNA (mRNA) has been hampered by the lack of a quantitative method that maps pseudouridine in the whole transcriptome. We report bisulfite-induced deletion sequencing (BID-seq) that utilizes a bisulfite-mediated reaction to stoichiometrically convert pseudouridine into deletion upon reverse transcription. BID-seq enabled detection of abundant pseudouridine sites with stoichiometry information in several human cell lines and 12 different mouse tissues using 10-20 ng input RNA. We uncovered consensus sequences for pseudouridine in mammalian mRNA and assigned different ‘writer’ proteins to individual pseudouridine deposition. Our results reveal a transcript stabilization role of Ψ sites installed by TRUB1 in human cancer cells. We also detected presence of Ψ within stop codons of mammalian mRNA, and confirmed the role of Ψ in promoting stop codon read-through in vivo. This new method for sensitive and comprehensive detection of Ψ sets the stage for future investigations of the roles of Ψ in diverse biological processes.

overall_design:
[dataset1] 20 samples (Sample 1-20): "Input" and "Treated" samples in BID-seq to detect pseudouridine in polyA+ RNA from HeLa cells of shControl and 8 human PUS synthase knockdown. (5′ SR Adapter: 5′-GUUCAGAGUUCUACAGUCCGACGAUC NNNNN-3′; See instructions of each sample about 3' SR Adapter sequences)
[dataset3] 48 samples (Sample 41-88): "Input" and "Treated" samples in BID-seq to detect pseudouridine in polyA+ RNA from 12 mouse tissues. (5′ SR Adapter: 5′-GUUCAGAGUUCUACAGUCCGACGAUC NNNNN-3′; See instructions of each sample about 3' SR Adapter sequences)
[dataset4] 18 samples (Sample 89-106): "Input" and "Treated" samples in BID-seq to detect pseudouridine in polyA+ RNA from wild-type HeLa, HEK293T and A549 cells. (5′ SR Adapter: 5′-GUUCAGAGUUCUACAGUCCGACGAUC-3′; See instructions of each sample about 3' SR Adapter sequences)

first: Qing

last: Dai

first: Chuan

last: He


title: Proliferating microglia integrate regulation of a core set of cell cycle genes with broader, context-dependent transcriptional programs

status: Public on Aug 18 2022

city: Québec

first: David

last: Gosselin

state: Quebec

address: CRCHUL - 2705 Boulevard Laurier, Bloc T - 2-34

department: Molecular Medicine

country: Canada

institute: Université Laval

summary: We report on the epigenomic and transcriptional programs associated with microglial proliferation in the brain. Gene expression profiles and genomic regulatory elements activity were determined on a genome-wide level. Data indicated that while the overall transcriptional out of proliferating microglia is context-dependent, a core signature of cell cycle genes accompanies proliferation across conditions. Furthermore, expression of these may be coordinated by one of two modes of regulation. A first mode augments expression of genes already expressed in quiescent microglia and is subject to regulation by Klf/Sp, Nfy, and Ets transcription factors. Alternatively, a second mode enables de novo gene transcription and requires additional regulatory input from Lin54 and E2f factors.

overall_design: Proliferating microglia were isolated from various contexts, and their H3K27ac (ChIP-seq) and gene expression (RNA-seq) profiles were compared. Additional analyses with H3K4me3 (ChIP-seq), RNA polymerase II subunit B (ChIP-seq) and ATAC-seq were also performed to characterize the underlying regulatory mechanisms at the chromatin level.


title: PABPN1 promotes meiotic maturation of oocytes by interacting with PAPOLA

status: Public on Aug 23 2022

city: Hangzhou

first: Xingxing

address: YuHangTang 866

institute: Life Sciences Institute

summary: Poly(A) polymerase α (PAPα), as the specific mRNA polyadenylation enzyme in the cytoplasm of mammalian oocytes, is essential for oocytes to exclude the first polar body. However, PAPα knockout did not affect germinal vesicles breakdown (GVBD) of oocytes, and the mechanism needs to be further explored. In this study, we identified that PAPα work together with poly(A)-bound RNA binding protein PABPN1 to promote the rupture of germinal vesicles in mammalian oocytes. The protein level of Pabpn1 gradually increases with the meiotic maturation of oocytes. The oocytes specifically knocked out Pabpn1 at the primary follicle stage could develop into the fully grown (FGO) stage, but hardly could enter into the meiotic process. The activated form of CDK1 was injected into Pabpn1-null oocytes, the oocytes could enter into meiotic process. The translational activity of Pabpn1-null oocytes was significantly lower than that of wild-type oocytes during meiosis. In particular, the expression level of protein (BTG4 and CDC25), which were essential for the meiotic maturation of oocytes, were significantly decreased. Therefore, during the oocyte meiosis process, PABPN1 and PAPα jointly promote the oocyte to enter the meiosis process.

overall_design: Examination of WT and Pabpn1-null  transcriptome in oocytes

first: Xing-Xing

first: Shuai-Bo

last: Pi

first: Yun-Wen

last: Wu


title: Physiological glucocorticoid receptor activation programs key cell phenotypes and functional epigenomic patterns in human fibroblasts [EPIC]

status: Public on Aug 15 2022

city: Providence

first: Calvin

last: Leung

address: 70 Ship Street

department: MCB

institute: Brown University

type: Methylation profiling by genome tiling array

summary: Chronic environmental stress can profoundly impact cell and body function. While the underlying mechanisms are poorly understood, epigenetics has emerged as a key link between environment and health. The genomic effects of stress are thought to be mediated by the action of glucocorticoid stress hormones, primarily cortisol in humans, which act via the glucocorticoid receptor (GR). To dissect how physiological GR activation influences epigenetic and cell states, human fibroblasts underwent prolonged exposure to physiological stress levels of cortisol and/or a selective GR antagonist. Cortisol was found to drive robust changes in cell proliferation, migration, and morphology, which were abrogated by concomitant GR blockade. These GR-driven phenotypes were accompanied by widespread, yet genomic context-dependent, changes in DNA methylation and mRNA expression involving genes with known roles in cell proliferation and migration. These findings provide novel insights into how chronic stress-driven functional epigenomic patterns become established to shape key cell phenotypes.

overall_design: EPIC array data of 4 IMR 90 samples with 6 biological replicates each were analyzed: vehicle, cortisol, relacorilant, and cortisol + relacorilant.

first: C

first: O

last: Kosyk

first: E

last: Welter

first: N

last: Dietrich

first: T

middle: K

last: Archer

first: A

last: Zannas


title: Physiological glucocorticoid receptor activation programs key cell phenotypes and functional epigenomic patterns in human fibroblasts [RNA-seq]

overall_design: RNA sequence data of 4 IMR 90 samples with 6 biological replicates each were analyzed: vehicle, cortisol, relacorilant, and cortisol + relacorilant.


title: Dioxin-elicited decrease in cobalamin redirects hepatic propionyl-CoA metabolism to the β–oxidation-like pathway resulting in acrylyl-CoA conjugate accumulation

status: Public on Aug 05 2022

city: East Lansing

first: Tim

last: Zacharewski

state: Michigan

address: 1129 Farm Ln

department: Biochemistry and Molecular Biology, Integrative Toxicological Sciences

institute: Michigan State University

summary: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant which induces diverse biological and toxic effects, including the reprograming of intermediate metabolism, mediated by the aryl hydrocarbon receptor (AHR). Targeted LC-MS analysis of hepatic extracts from mice gavaged with TCDD every 4 days for 28 days detected an increase in S-(2-carboxyethyl)-L-cysteine, a conjugate produced following the spontaneous reaction between the sulfhydryl group of cysteine and highly reactive acrylyl-CoA, an intermediate in the cobalamin (Cbl)-independent β–oxidation-like metabolism of propionyl-CoA.  In addition to repressing genes in both the canonical Cbl-dependent carboxylase and the alternate Cbl-independent β–oxidation-like pathways at 30 µg/kg TCDD, methylmalonyl-CoA mutase (MUT) activity was inhibited at lower doses. Moreover, TCDD decreased serum Cbl levels and hepatic cobalt levels while eliciting negligible effects on gene expression associated with Cbl absorption, transport, trafficking, or the derivatization to 5’-deoxy-adenosylcobalamin (AdoCbl), the required MUT cofactor. In addition to inducing Acod1 that encodes for aconitate decarboxylase 1, the enzyme responsible for the decarboxylation cis-aconitate to itaconate, TCDD also dose-dependently increased itaconate levels in hepatic extracts. MUT inhibition is consistent with itaconate activation to itaconyl-CoA, a MUT suicide inactivator that adducts AdoCbl, that in turn, inhibits MUT activity and reduces Cbl levels. Collectively, these results suggest the decrease in MUT activity is due to Cbl depletion following TCDD treatment that redirected propionyl-CoA metabolism to the alternate Cbl-independent β–oxidation-like pathway. The resulting hepatic accumulation of acrylyl-CoA likely contributes to TCDD-elicited hepatotoxicity and the multi-hit progression of steatosis to steatohepatitis with fibrosis.

overall_design: Beginning on post-natal day (PND) 30, male C57BL/6 mice were repeatedly gavaged at 23° C every 4 days for 28 days with some dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (0.03 - 30 µg/kg TCDD) or sesame oil vehicle (n = 5 per dose) and sacrificed on PND 58 with CO2. Gavaging and tissue collection always occurred between ZT0 and ZT3. Tissues were flash frozen in liquid nitrogen and stored at -80°C. For total RNA extraction using trizol, 100 mg was used per liver sample. Only samples which passed Nanodrop and RIN quality control were used. 150 bp paired-end RNA reads were sequenced using a NovoSeq 6000.

first: Warren

last: Sink

first: Rance

last: Nault


title: Physiological glucocorticoid receptor activation programs key cell phenotypes and functional epigenomic patterns in human fibroblasts [TBS]

overall_design: Targeted bisulfite sequencing (TBS) data of 2 IMR90 samples with 6 biological replicates were analyzed: vehicle and cortisol. 8 dermal fibroblasts samples with 1 biological replicate: vehicle and cortisol.


title: Histone ChIP-seq from middle frontal area 46 (ENCSR691JHZ)

status: Public on Jul 22 2022

city: Stanford

first: ENCODE

last: DCC

address: 300 Pasteur Dr

institute: ENCODE DCC

summary: 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: Chronic stress-driven glucocorticoid receptor activation programs key cell phenotypes and functional epigenomic patterns in human fibroblasts

status: Public on Aug 11 2022

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

overall_design: Refer to individual Series


title: Histone ChIP-seq from middle frontal area 46 (ENCSR857HWF)


title: Histone ChIP-seq from middle frontal area 46 (ENCSR852AYS)

summary:
H3K27me3 ChIP-seq on middle frontal area 46 tissue female adult (90 or above years)

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: Histone ChIP-seq from middle frontal area 46 (ENCSR406AJH)

summary:
H3K4me3 ChIP-seq on middle frontal area 46 tissue female adult (82 years)

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: Histone ChIP-seq from middle frontal area 46 (ENCSR185BMK)


title: Histone ChIP-seq from middle frontal area 46 (ENCSR858ASK)

summary:
H3K27me3 ChIP-seq on middle frontal area 46 tissue female adult (90 or above years) with Alzheimer's disease.

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: Histone ChIP-seq from middle frontal area 46 (ENCSR634DME)

summary:
H3K27me3 ChIP-seq on middle frontal area 46 tissue female adult (89 years) with Alzheimer's disease

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: Histone ChIP-seq from middle frontal area 46 (ENCSR762RMQ)

summary:
H3K27me3 ChIP-seq on middle frontal area 46 tissue female adult (82 years)

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: Histone ChIP-seq from middle frontal area 46 (ENCSR128SVE)


title: Histone ChIP-seq from middle frontal area 46 (ENCSR157MPY)


title: Histone ChIP-seq from middle frontal area 46 (ENCSR567VAB)


title: Histone ChIP-seq from middle frontal area 46 (ENCSR706PAK)

summary:
H3K27me3 ChIP-seq on middle frontal area 46 tissue female adult (79 years)

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: Histone ChIP-seq from middle frontal area 46 (ENCSR914ETY)


title: Histone ChIP-seq from middle frontal area 46 (ENCSR981TFL)

summary:
H3K4me3 ChIP-seq on middle frontal area 46 tissue female adult (90 or above years)

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: Histone ChIP-seq from middle frontal area 46 (ENCSR252TQC)


title: Glucagon-like Peptide-1 (GLP-1) Rescue Diabetic Cardiac Dysfuntions in Human iPSC-Derived Cardiomyocytes

status: Public on Jul 01 2022

city: nanjing

first: Ying

last: Zhou

address: 101 longmian street

institute: Nanjing Medical university

summary: We investigate the effects of GLP-1 on diabetic cardiomyocytes (DCMs) model established by human induced pluripotent stem cells-derived cardiomyocytes (iPSC-CMs). Two subtypes of GLP-1, GLP-17-36 and GLP-19-36, were evaluated for their efficacy on hypertrophic phenotype, impaired calcium homeostasis and electrophysiological properties. RNA-seq was performed to reveal the underlying molecular mechanism of GLP-1. Our results demonstrated that GLP-17-36 and GLP-19-36 were able to ameliorate high glucose-induced hypertrophy phenotype and cardiac dysfunctions in DCM model based on iPSC-CMs. Our study provides a novel platform to unveil the cellular mechanisms of diabetic cardiomyopathy, which sheds light on discovering better targets for novel therapeutic interventions.

overall_design: CM control group ( iPSC-CMs,n=4 ), DCM model group (diabetic cardiomyocytes,n=4), GLP-17-36 treatment group (diabetic cardiomyocytes treated with  GLP-17-36,n=4), GLP-19-36 treatment group (diabetic cardiomyocytes treated with GLP-19-36,n=4)

first: Yu

last: Liu

first: Jiaxian

last: Wang

first: Yue

last: Qiao


title: Gene expression profile at single cell level of tumor dissociated cells from OS1 PDX tumors after control-PBMC or attIL12-PBMC treatment

status: Public on Jun 16 2022

city: Houston

first: Jiemiao

last: Hu

address: 1515 Holcombe Blvd

institute: UT MD Anderson Cancer Cener

summary: We performed single cell RNAseq to explore the molecular changes in cellular composition induced by attIL12-PBMC infusion in OS1 PDX tumors.

overall_design: The OS1 fresh tumors were minced and dissociated with mixed enzymes, removed red blood cells and analyzed with single cell RNAseq.

first: Qing

last: Yang

first: Zhiliang

last: Jia

first: Qi

first: Jing

first: Long

last: Dao

first: Wendong

last: Zhang

first: Sheng

first: Xueqing

last: Xia

first: Richard

last: Gorlick

first: Shulin

last: Li


title: Histone ChIP-seq from middle frontal area 46 (ENCSR888EEH)

summary:
H3K4me3 ChIP-seq on middle frontal area 46 tissue female adult (89 years) with Alzheimer's disease

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: Transcriptome of epibiont Saccharibacteria TM7x during establishment of symbiosis on host Schaalia odontolyticus strain XH001

status: Public on Jul 18 2022

city: Seattle

first: Jeffrey

last: McLean

state: WA

address: 1959 NE Pacific St, Box 357444

department: Periodontics

institute: University of Washington

summary: Nanosynbacter lyticus type strain TM7x  was the first cultivated member of the broadly prevelent, but poorly udnerstood Candidate Phylum Radiation super-phylum. TM7x was shown to be an obligate epibiont with a host range including Schaalia odontolyticus strain XH001. The process of infecting a naive host goes through multiple phases, from an initial  binding and interaction phase we call the initial encounter, to a rapid die off of infected host cells, killing phase, followed by regrowth of the host cells, regrowth phase, and finally a stable symbiosis between the species, stable symbiosis.To obtain a better understanding of the process by which these species establish a stable symbiosis, we measured the transcriptome using RNA sequencing across the course of infection. We sampled infected host, XH001/TM7x, during the initial interaction, regrowth, and after attaining stable symbiosis, as well as naive host controls grown under the same culture conditions.

sample_organism:
Schaalia odontolytica
Candidatus Nanosynbacter lyticus

overall_design: Free TM7x was isolated from infected XH001 hosts. Naive hosts were then exposed to free TM7x and grown for in Brain Heart Infusion media and passaged every 24 hours into new media at an OD600 of 0.1. Naive XH001 was grown using the same passaging as a control. Samples were collected from both XH001/ TM7x and the control 6 hours into passage 0, representing the initial encounter phase, 6, 10, and 15 hours into passage 4, representing the regrowth phase, and 6 hours into passage 6, representing the stable symbiosis phase. Samples were collected in triplicate.

first: Erik

last: Hendrickson

first: Batbileg

last: Bor

first: Kristopher

last: Kerns

first: Eleanor

middle: I

last: Lamont

first: Lujia

last: Cen

first: Wenyuan

last: Shi

first: Xuesong

last: He

first: Jeffery


title: Expression data from mouse dendritic cells (cDCs)

status: Public on Jun 14 2022

city: Perugia

first: Marco

last: Gargaro

state: Perugia

address: Polo Unico Sant'Andrea delle Fratte, P.le Gambuli, Bldg C, 4th Floor

department: Medicine and Surgery

country: Italy

institute: University of Perugia

summary: We used microarrays to understand  the role of LPS in inducing tolerogenic enzymes in DC subsets

overall_design: WT bone marrow derived DCs (BMDCs) were sort-purified and treated with LPS for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain gene expression signature that are controlled by LPS in DC subtypes

first: Kenneth

last: Murphy

first: Francesca

last: Fallarino


title: Role of Epigenetics in the Etiology of Hypospadias through Foreskin DNA Methylation Alterations

status: Public on Jun 01 2022

city: Pullman

first: Michael

last: Skinner

address: Abelson 507

department: SBS

institute: WSU

summary: Abnormal foreskin and penile development in hypospadias is the most frequent genital malformation in male children, which has increased dramatically in recent decades. Environmental factors (i.e., endocrine disruptors) have been shown to be associated with hypospadias development. The current study investigated the role of epigenetics in the etiology of hypospadias and compared mild, moderate, and severe hypospadias. Dramatic numbers of differential DNA methylation regions (DMRs) were observed in the mild hypospadias, with reduced numbers in moderate and low numbers in severe hypospadias. Atresia (cell loss) of the principal foreskin fibroblast is suspected to be the cause.

overall_design: This study was designed to collect foreskin fibroblasts from mild, moderate, and severe hypospadias male patients and compare with foreskin from non-disease control population patients. The DNA methylation in the foreskin cell populations was assessed using MeDIP-seq and compared to identify differential DNA methylation regions (DMRs) associated with hypospadias disease etiology.

first: Martin

last: Kaefer

first: Paul

last: Winchester

first: Millissia

last: Ben Maamar

first: Daniel

last: Beck

first: Eric

last: Nilsson


title: Cholesterol and matrisome pathways dysregulated in APOE ε4 human microglia and astrocytes [mouseApoe]

status: Public on Jun 23 2022

city: Boston

first: Julia

last: TCW

state: Massachusetts

address: 700 Albany St.

institute: Boston University

summary: The impact of Apolipoprotein E4 (APOE4), the strongest genetic risk factor for Alzheimer's disease (AD), on human brain cellular function remains unclear. Here we investigated the effects of APOE4 on brain cell types derived from population and isogenic human induced pluripotent stem cell models, post-mortem brain and APOE targeted replacement mice. Population and isogenic models uncover that APOE4 local haplotype rather than a single risk allele alone contributes to the risk. Global transcriptomic analyses reveal human specific, APOE4-driven lipid metabolic dysregulation in astrocytes and microglia. APOE4 leads to elevated de novo cholesterol synthesis despite the intracellular cholesterol accumulation due to lysosomal sequestration of cholesterol in astrocytes. Transcriptome analyses uncovered Matrisome dysregulation associated with upregulated chemotaxis, glial activation and lipid biosynthesis in astrocytes, co-cultured with neurons that recapitulates altered astrocyte matrisome signaling in human brain. Thus, APOE4 initiates glia-specific cell and non-cell autonomous dysregulation that may contribute to increased AD risk.

overall_design: We performed bulk RNA-sequencing on population iPSC-derived, CRISPR-edited isogenic iPSC-derived astrocytes, microglia, mixed cortical cultures, BMECs from APOE 33 vs APOE 44 and mouse astrocytes and microglia from APOE 33, APOE 44, Apoe WT and Apoe KO. This particular dataset is mouse APOE33, APOE44, Apoe WT and Apoe KO.

first: Alison

last: Goate

first: Wayne

last: Poon


title: Single-cell transcriptomic and proteomic analysis of Parkinson’s disease brains

city: New Haven

first: Le

last: Zhang

state: CT

address: 300 George Street

department: Neurology

institute: Yale University

summary: Parkinson’s disease (PD) is a prevalent neurodegenerative disorder where recent evidence suggests pathogenesis may be mediated by inflammatory processes. The molecular architecture of the disease remains to be fully elucidated. We performed single-nucleus transcriptomics and unbiased proteomics using postmortem tissue obtained from the prefrontal cortex of 12 individuals with late-stage PD and age-matched controls. We analyzed ~80,000 nuclei and identified eight major cell types, including brain-resident T cells, each with distinct transcriptional changes in line with the known genetics of PD. By analyzing Lewy body pathology in the same postmortem tissue, we found that α-synuclein pathology is inversely correlated with chaperone expression in excitatory neurons. Examining cell-cell interactions, we found a selective abatement of neuron-astrocyte interactions and enhanced neuroinflammation. Proteomic analyses of the same brains identified synaptic proteins in prefrontal cortex that were preferentially downregulated in PD. Strikingly, comparing this dataset to a regionally similar published analysis for Alzheimer’s disease (AD), we found no common differentially expressed genes in neurons, but identified many shared differentially expressed genes in glial cells, suggesting that disease etiology in PD and AD are likely distinct. These data are presented as a resource for interrogating the molecular and cellular basis of PD and other neurodegenerative diseases.

overall_design: From 12 individuals with and without PD, we isolated brain nuclei from prefrontal cortex by sucrose gradient ultracentrifugation, generated single nucleus libraries with 10x Chromium platform (10x Genomics), and sequenced on NovaSeq6000 S4 sequencer (Illumina).

first: Sreeganga

last: Chandra

first: David

last: Hafler


title: Cholesterol and matrisome pathways dysregulated in APOE ε4 human microglia and astrocytes


title: Mettl3-mediated m6A modification controls postnatal liver development by modulating Hnf4a-centred regulatory network [m6A-RIP-RNA-seq]

status: Public on May 26 2022

city: Guangzhou

first: Yan

last: Xu

state: Guangdong

address: No. 600 Tianhe Road

institute: The Third Affiliated Hospital of Sun Yat-Sen University

summary: m6A-RIP sequencing of mouse liver tissues at different time points after birth.

overall_design: WT mouse liver tissues were collected separately at day 1, 1 week, 2 weeks, 4 weeks and 8 weeks after birth. mRNA was purified from total RNA for m6A-RIP sequencing. m6A peaks were analyzed at different postnatal liver development stages.

first: Xinmei

last: Kang

first: Zhuowei

last: Zhou

first: Qi


title: The MLL-Menin interaction is a molecular dependency in NUP98-rearranged AML [ChIP-Seq]

first: Scott

last: Armstrong

state: MA

address: 450 Brookline Ave

department: pediatric oncology

institute: Dana Farber Cancer Institute

summary: Using mouse and human models of NUP98-rearrranged leukemia, we demonstrate that inhibition of MLL-Menin impairs leukemogenic gene expression and  disrupts chromatin binding of MLL1 and NUP98 fusion proteins at a critical subset of genes that is essential for sustaining the undifferentiated leukemia phenotype.

overall_design: Examination of gene expression changes in mouse leukemia cells treated with the MLL-Menin inhibitor VTP50469

first: Emily

middle: B

last: Heikamp

first: Charlie

last: Hatton


title: The MLL-Menin interaction is a molecular dependency in NUP98-rearranged AML

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


title: Histone ChIP-seq from middle frontal area 46 (ENCSR010HNY)

first: ENCODE

last: DCC

summary: 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 MLL-Menin interaction is a molecular dependency in NUP98-rearranged AML [BioChIP-seq]


title: Transcriptome and 3D genome sequencing depict the regulation of K5aSE

status: Public on May 12 2022

city: Tianjin

first: Niannian

last: Li

state: Tianjin

address: No. 94 Weijin Road, Nankai District, Tianjin

department: college of Life Sciences

institute: Nankai University

summary:
Purpose: Super-enhancers (SEs) have been reported to regulate the expression of core transcription factors in embryonic stem cells (ESCs), but they have not been well identified and evaluated in terms of their functional roles in ESC phenotype.
Methods and results: Here we identified an ESC-specific Klf5-adjacent SE (K5aSE) by conducting comprehensive analysis of ESCs in different states. We found that K5aSE is required for ESC clonal growth, cell proliferation, embryoid body (EB) differentiation and Klf5 expression. However, restorative expression of Klf5 only partially rescued the phenotype of K5aSE knockout (K5aSE-KO) ESCs. Meanwhile, Klf5-KO ESCs exhibited similar phenotypes to K5aSE-KO cells, but shown different lineage differentiation in EBs, revealing that K5aSE and Klf5 regulate ESCs differently. Further 4C-seq combined with RNA-seq analysis showed that K5aSE significantly promoted the expression of other four target genes in the same chromosome, such as Clybl, Farp1, Nkx3-1 and Tbc1d4, and that CRISPRa-mediated restoration of these four genes also partially rescued the phenotype of K5aSE-KO cells. Finally, we also identified these four genes as novel ESC regulators required for self-renewal and EB differentiation.  transcripts in the retinas of WT and Nrl−/− mice with BWA workflow and 34,115 transcripts with TopHat workflow. RNA-seq data confirmed stable expression of 25 known housekeeping genes, and 12 of these were validated with qRT–PCR. RNA-seq data had a linear relationship with qRT–PCR for more than four orders of magnitude and a goodness of fit (R2) of 0.8798. Approximately 10% of the transcripts showed differential expression between the WT and Nrl−/− retina, with a fold change ≥1.5 and p value <0.05. Altered expression of 25 genes was confirmed with qRT–PCR, demonstrating the high degree of sensitivity of the RNA-seq method. Hierarchical clustering of differentially expressed genes uncovered several as yet uncharacterized genes that may contribute to retinal function. Data analysis with BWA and TopHat workflows revealed a significant overlap yet provided complementary insights in transcriptome profiling.
Conclusions: Together, this study provides new insights into understanding ESC properties and highlights the crucial role of SE as 3D chromatin structure-dependent transcriptional driver in ESCs.

overall_design: At least 2 biological replicates were analyzed for each experimental condition. WT and knockout cells were RNA-seq in ESCs or EBs-day 5. 4C-seq of K5aSE were done in ESCs.

first: Wange

last: Lu

first: Guangsong

last: Su

first: Wenbin

last: Wang