23037
2020
eng
21
article
1
2021-03-10
--
--
Comparison of the central human and mouse platelet signaling cascade by systems biological analysis
Background
Understanding the molecular mechanisms of platelet activation and aggregation is of high interest for basic and clinical hemostasis and thrombosis research. The central platelet protein interaction network is involved in major responses to exogenous factors. This is defined by systemsbiological pathway analysis as the central regulating signaling cascade of platelets (CC).
Results
The CC is systematically compared here between mouse and human and major differences were found. Genetic differences were analysed comparing orthologous human and mouse genes. We next analyzed different expression levels of mRNAs. Considering 4 mouse and 7 human high-quality proteome data sets, we identified then those major mRNA expression differences (81%) which were supported by proteome data. CC is conserved regarding genetic completeness, but we observed major differences in mRNA and protein levels between both species. Looking at central interactors, human PLCB2, MMP9, BDNF, ITPR3 and SLC25A6 (always Entrez notation) show absence in all murine datasets. CC interactors GNG12, PRKCE and ADCY9 occur only in mice. Looking at the common proteins, TLN1, CALM3, PRKCB, APP, SOD2 and TIMP1 are higher abundant in human, whereas RASGRP2, ITGB2, MYL9, EIF4EBP1, ADAM17, ARRB2, CD9 and ZYX are higher abundant in mouse. Pivotal kinase SRC shows different regulation on mRNA and protein level as well as ADP receptor P2RY12.
Conclusions
Our results highlight species-specific differences in platelet signaling and points of specific fine-tuning in human platelets as well as murine-specific signaling differences.
BMC Genomics
10.1186/s12864-020-07215-4
urn:nbn:de:bvb:20-opus-230377
publish
BMC Genomics (2020) 21:897 https://doi.org/10.1186/s12864-020-07215-4
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Johannes Balkenhol
Kristin V. Kaltdorf
Elmina Mammadova-Bach
Attila Braun
Bernhard Nieswandt
Marcus Dittrich
Thomas Dandekar
eng
uncontrolled
interspecies comparison
eng
uncontrolled
transcriptome
eng
uncontrolled
proteome
eng
uncontrolled
platelet
eng
uncontrolled
network
eng
uncontrolled
signaling
eng
uncontrolled
mouse
eng
uncontrolled
human
eng
uncontrolled
interactome
eng
uncontrolled
cascade
Biowissenschaften; Biologie
open_access
Theodor-Boveri-Institut für Biowissenschaften
Rudolf-Virchow-Zentrum
Institut für Experimentelle Biomedizin
Förderzeitraum 2020
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/23037/s12864-020-07215-4.pdf
16291
2016
eng
e15161
5
article
1
2018-06-15
--
--
Different promoter affinities account for specificity in MYC-dependent gene regulation
Enhanced expression of the MYC transcription factor is observed in the majority of tumors. Two seemingly conflicting models have been proposed for its function: one proposes that MYC enhances expression of all genes, while the other model suggests gene-specific regulation. Here, we have explored the hypothesis that specific gene expression profiles arise since promoters differ in affinity for MYC and high-affinity promoters are fully occupied by physiological levels of MYC. We determined cellular MYC levels and used RNA- and ChIP-sequencing to correlate promoter occupancy with gene expression at different concentrations of MYC. Mathematical modeling showed that binding affinities for interactions of MYC with DNA and with core promoter-bound factors, such as WDR5, are sufficient to explain promoter occupancies observed in vivo. Importantly, promoter affinity stratifies different biological processes that are regulated by MYC, explaining why tumor-specific MYC levels induce specific gene expression programs and alter defined biological properties of cells.
eLife
10.7554/eLife.15161
PMC4963202
urn:nbn:de:bvb:20-opus-162913
eLife 2016;5:e15161. DOI: 10.7554/eLife.15161
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Francesca Lorenzin
Uwe Benary
Apoorva Baluapuri
Susanne Walz
Lisa Anna Jung
Björn von Eyss
Caroline Kisker
Jana Wolf
Martin Eilers
Elmar Wolf
eng
uncontrolled
MYC
eng
uncontrolled
promoter affinity
eng
uncontrolled
human
eng
uncontrolled
mathematical modeling
eng
uncontrolled
mouse
eng
uncontrolled
ChIP-sequencing
eng
uncontrolled
MIZ1
eng
uncontrolled
cancer biology
eng
uncontrolled
cell biology
eng
uncontrolled
WDR5
Medizin und Gesundheit
open_access
Theodor-Boveri-Institut für Biowissenschaften
Theodor-Boveri-Institut für Biowissenschaften
Rudolf-Virchow-Zentrum
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16291/Lorenzin_eLife_2016.pdf
13065
2012
eng
e50985
12
7
article
1
2016-03-24
--
--
Identification of New Therapeutic Targets by Genome-Wide Analysis of Gene Expression in the Ipsilateral Cortex of Aged Rats after Stroke
Background: Because most human stroke victims are elderly, studies of experimental stroke in the aged rather than the young rat model may be optimal for identifying clinically relevant cellular responses, as well for pinpointing beneficial interventions.
Methodology/Principal Findings: We employed the Affymetrix platform to analyze the whole-gene transcriptome following temporary ligation of the middle cerebral artery in aged and young rats. The correspondence, heat map, and dendrogram analyses independently suggest a differential, age-group-specific behaviour of major gene clusters after stroke. Overall, the pattern of gene expression strongly suggests that the response of the aged rat brain is qualitatively rather than quantitatively different from the young, i.e. the total number of regulated genes is comparable in the two age groups, but the aged rats had great difficulty in mounting a timely response to stroke. Our study indicates that four genes related to neuropathic syndrome, stress, anxiety disorders and depression (Acvr1c, Cort, Htr2b and Pnoc) may have impaired response to stroke in aged rats. New therapeutic options in aged rats may also include Calcrl, Cyp11b1, Prcp, Cebpa, Cfd, Gpnmb, Fcgr2b, Fcgr3a, Tnfrsf26, Adam 17 and Mmp14. An unexpected target is the enzyme 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 in aged rats, a key enzyme in the cholesterol synthesis pathway. Post-stroke axonal growth was compromised in both age groups.
Conclusion/Significance: We suggest that a multi-stage, multimodal treatment in aged animals may be more likely to produce positive results. Such a therapeutic approach should be focused on tissue restoration but should also address other aspects of patient post-stroke therapy such as neuropathic syndrome, stress, anxiety disorders, depression, neurotransmission and blood pressure.
PLoS One
10.1371/journal.pone.0050985
urn:nbn:de:bvb:20-opus-130657
PLoS ONE 7(12): e50985. doi:10.1371/journal.pone.0050985
Ana-Maria Buga
Claus Jürgen Scholz
Senthil Kumar
James G. Herndon
Dragos Alexandru
Gabriel Radu Cojocaru
Thomas Dandekar
Aurel Popa-Wagner
eng
uncontrolled
gamma
eng
uncontrolled
corticotropin-releasing hormone
eng
uncontrolled
colony-stimulating factor
eng
uncontrolled
cerebral ischemia
eng
uncontrolled
receptor
eng
uncontrolled
brain
eng
uncontrolled
protein
eng
uncontrolled
inhibitor
eng
uncontrolled
mouse
eng
uncontrolled
differentiation
Datenverarbeitung; Informatik
Biowissenschaften; Biologie
open_access
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/13065/journal.pone.0050985.pdf
13341
2013
eng
e59400
3
8
article
1
2016-05-12
--
--
p53 Gene Targeting by Homologous Recombination in Fish ES Cells
Background: Gene targeting (GT) provides a powerful tool for the generation of precise genetic alterations in embryonic stem (ES) cells to elucidate gene function and create animal models for human diseases. This technology has, however, been limited to mouse and rat. We have previously established ES cell lines and procedures for gene transfer and selection for homologous recombination (HR) events in the fish medaka (Oryzias latipes).
Methodology and Principal Findings: Here we report HR-mediated GT in this organism. We designed a GT vector to disrupt the tumor suppressor gene p53 (also known as tp53). We show that all the three medaka ES cell lines, MES1 similar to MES3, are highly proficient for HR, as they produced detectable HR without drug selection. Furthermore, the positive-negative selection (PNS) procedure enhanced HR by similar to 12 folds. Out of 39 PNS-resistant colonies analyzed, 19 (48.7%) were positive for GT by PCR genotyping. When 11 of the PCR-positive colonies were further analyzed, 6 (54.5%) were found to be bona fide homologous recombinants by Southern blot analysis, sequencing and fluorescent in situ hybridization. This produces a high efficiency of up to 26.6% for p53 GT under PNS conditions. We show that p53 disruption and long-term propagation under drug selection conditions do not compromise the pluripotency, as p53-targeted ES cells retained stable growth, undifferentiated phenotype, pluripotency gene expression profile and differentiation potential in vitro and in vivo.
Conclusions: Our results demonstrate that medaka ES cells are proficient for HR-mediated GT, offering a first model organism of lower vertebrates towards the development of full ES cell-based GT technology.
PLoS One
10.1371/journal.pone.0059400
urn:nbn:de:bvb:20-opus-133416
PLoS ONE 8(3): e59400. doi:10.1371/journal.pone.0059400
Yan Yan
Ni Hong
Tiansheng Chen
Mingyou Li
Tiansu Wang
Guijun Guan
Yongkang Qiao
Songlin Chen
Manfred Schartl
Chang-Ming Li
Yunhan Hong
eng
uncontrolled
mouse
eng
uncontrolled
in-vitro
eng
uncontrolled
drug selection
eng
uncontrolled
chimera formation
eng
uncontrolled
medakafish oryzias latipes
eng
uncontrolled
embryonic stem-cells
eng
uncontrolled
zebrafish
eng
uncontrolled
differentiation
eng
uncontrolled
cultures
eng
uncontrolled
pluripotency
Physiologie und verwandte Themen
open_access
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/13341/090_Yan_Plos_One.pdf
6263
2011
eng
article
1
2012-11-15
--
--
Expression of individual mammalian Sun1 isoforms depends on the cell type
Mammalian Sun1 belongs to an evolutionarily conserved family of inner nuclear membrane proteins, which are known as SUN domain proteins. SUN domain proteins interact with KASH domain partners to form bridging complexes, so-called LINC complexes, that physically connect the nuclear interior to the cytoskeleton. LINC complexes are critical for nuclear integrity and play fundamental roles in nuclear positioning, shaping and movement. The mammalian genome codes for at least five different SUN domain proteins used for the formation of a number of different LINC complexes. Recently, we reported on the identification of everal Sun1 isoforms, which tremendously enlarges the alternatives to form functional LINC complexes. We now confirmed that Sun1 actually exists in at least seven distinct splice variants. Besides that, we observed that expression of individual Sun1 isoforms remarkably depends on the cell type, suggesting a cell type-specific adaption of Sun1 dependent LINC complexes to specific cellular and physiological requirements.
urn:nbn:de:bvb:20-opus-68750
6875
In: Communicative & Integrative Biology (2011) 4:4, 440-442, doi: 10.4161/cib.4.2.15369
Eva Göb
Elisabeth Meyer-Natus
Ricardo Benavente
Manfred Alsheimer
deu
swd
Biologie
eng
uncontrolled
Sun1
eng
uncontrolled
SUN domain protein
eng
uncontrolled
LINC complex
eng
uncontrolled
mouse
eng
uncontrolled
nuclear envelope
eng
uncontrolled
isoform
Biowissenschaften; Biologie
open_access
Theodor-Boveri-Institut für Biowissenschaften
Förderzeitraum 2011
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/6263/Alsheimer100_cib0404_0440.pdf