Hao Yin @HaoYin@qoto.org

Effects of #Aneuploidy on cell behavior & function

Cause:
ROS
DNA replication
mitosis
mechanical confinement

Direct dosage + secondary Effect:
Redox, bioenergetic, proteostasis, Osmosis
Cancer, Aging

Dr Rong Li & Jin Zhu Nature Reviews MCB 2023
https://www.nature.com/articles/s41580-021-00436-9

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Any evidence on #Aneuploidy in cardiovascular biology?

From Abraham Aviv lab @ATHjournal 2001

Age-dependent aneuploidy & telomere length of the human vascular endothelium
https://www.atherosclerosis-journal.com/article/S0021-9150(01)00506-8/fulltext

Tetrasomy Chr6 Chr16
Loss ChrY

Aneuploidy in cardiovascular diseases?🧐

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Mice with #SpindleAssemblyCheckpoint protein BubR1 deficiency have a spectrum of vascular defects

Vascular BubR1 1/3

Aging-Associated Vascular Phenotype in Mutant Mice With Low Levels of BubR1

Dr. Jan van Deursen lab @StrokeAHA_ASA 2007
https://www.ahajournals.org/doi/10.1161/01.STR.0000257967.86132.01

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Vascular BubR1 2/3

BubR1 Insufficiency Inhibits #NeointimalHyperplasia Through Impaired Vascular #SmoothMuscleCell Proliferation in Mice

Dr. Takuya Matsumoto lab @atvbahajournals 2014
https://www.ahajournals.org/doi/10.1161/ATVBAHA.114.304737
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Vascular BubR1 3/3

BubR1 insufficiency impairs #Angiogenesis in aging and in experimental critical limb ischemic mice

Dr. Takuya Matsumoto lab @JVascSurg 2018
https://www.jvascsurg.org/article/S0741-5214(17)32041-4/fulltext

CRISPR-activated Oct4 as #GeneTherapy for #Progeria (LmnaC698G) & natural aged🐭
#HutchinsonGilfordProgeriaSyndrome

Polyethylenimine-cationic gold nanoparticle iv.

Do we need an aortotropic vector for #AorticAneurysm?

Dr. Jongpil Kim lab @AgingCell 2023
https://onlinelibrary.wiley.com/doi/10.1111/acel.13825

Through Oct4 expression is only transiently activated for 2 weeks in 50% aortic SMCs (by day 5 delivery) in progeria mice, but with an amazing long-lasting benefits on SMC vitality, arterial stiffness, progerin, multi-organ ( kidney, spleen, muscle, lung, and skin) senescence transcriptional profile, lifespan w/o apparent dysplasia

IL-11 as a therapeutic target for lung #Fibrosis #Emphysema in #MarfanSyndrome

In Marfan🐭🫁, IL11-GFP reporter is active in #EndothelialCell #SmoothMuscleCell Fibroblast but not alveolar epithelia

Dr. Stuart A Cook & Wei Wen Lim lab ATVB 2023
https://www.ahajournals.org/doi/10.1161/ATVBAHA.122.318802

Also don't miss the story on IL-11 as mediator of Mafan #Aortopathy from Circ Res 2022

https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.121.320381

Epigenetics #PulmonaryArterialHypertension

JMJD1C a histone demethylase
⏫p-STAT3->
⏫#Glycolysis HK2/PGK1/LDHA->
⏫PA #SmoothMuscleCell Proliferation

Serum Lactate⏬by AAV2-shJMJD1C in🐭#Hypoxia-PAH
Local effect on #EndMT?

Dr H Zhao lab Cell Death Discovery 2023
https://www.nature.com/articles/s41420-023-01390-5

High-throughout (50) high-res (<1.9 µm/px) blood flow imaging of whole #Zebrafish 2-6 dpf

Geometry
Velocity
Hematocrit
Viscosity
#ShearStress

Visualize the devepmental correlation b/w flow & vascular hierarchy🤩

Dr. Li-Kun Phng lab Front Physiol 2022
https://www.frontiersin.org/articles/10.3389/fphys.2022.881929/full

A systematic map for zebrafish developmental hemodynamics🤓

"stratification order of median levels of WSSpeak b/w vessel types was maintained in the anterior half... the posterior half had a different WSSpeak hierarchy...b/w 6 & 2 dpf"

#Biomechanics in vascular morphogenesis

Human Meniscus single-cell RNAseq atlas
4 normal+4 #OsteoArthritis

5 #Chondroncyte subtypes
Emerging proliferative chondrocyte in degenerated tissue

OA-related #EndothelialCell/#MuralCell-Chondrocyte crosstalks🤓

Dr. W Fu & X Zhang labs @eLife 2023
https://elifesciences.org/articles/79585

Amh+ #SertoliCell is a major (80%) cellular source of #StemCellFactor in🐭Testis

Sertoli, Not #EndothelialCell SCF->
#Spermatogonia maintenance+differentiation

Cell-specific SCF Glycosylation? Proximity?🧐

Dr Hongfang Shao, Bo Zhou lab @Dev_journal 2023
https://journals.biologists.com/dev/article/doi/10.1242/dev.200706/293491/Sertoli-cells-are-the-unique-source-of-stem-cell

A highly intriguing #Hyperglycemia-#HyaluronicAcid-CD44-Survivin cascade dictates β-islet survival

4-methylumbelliferone, an HA biosynthesis inhibitor, protects diabetic🐭(db/db; STZ 40 mg) from hyperglycemia😎

Dr. Paul Bollyky lab BioRxiv 2023
https://www.biorxiv.org/content/10.1101/2023.02.28.530522v1.full

Want to know about this drug 4-methylumbelliferone/#Hymecromone?👇

4-Methylumbelliferone treatment and hyaluronan inhibition as a therapeutic strategy in inflammation, autoimmunity, and cancer

Front Immunol 2015
https://www.frontiersin.org/articles/10.3389/fimmu.2015.00123/full

A high-resolution transcriptomic & spatial atlas of cell types in the whole🐭brain

MERFISH+scRNAseq 10 M+ cells
#SciArt

I will need to sharpen my bioinfo🔪to take a close look into Vascular Division🤖

Dr. Hongkui Zeng lab BioRxiv 2023
https://www.biorxiv.org/content/10.1101/2023.03.06.531121v1

A methodological frame to optimize antibody staining of #CLARITY-cleared human brain

"...even a small increase in PFA exposure can have significant influence on IHC quality and depth"

Lots of important empirical points

Dr. Theodore Zwang lab eLife 2023
https://elifesciences.org/articles/84112

#Sirt6 deacetylates #YAP & #TAZ->
⏬their transcriptional activities
⏬TGFβ1-induced Fibrotic reprogramming of #HepaticStellateCell
in diet-induced🐭#LiverFibrosis

TAZ seems more sensitive to Sirt6 than YAP🤓

#MALFD

Dr. Charlie Dong lab FASEB J 2022
https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/fj.202200522R

AP-1 transcription factors ATF3/FOSL1/FOSL2/c-JUN reshape Chromatin Accessibility landscape during #EndothelialCell #Senescence

HUVEC PD 8vs24vs36
1038 & 964 increased & decreased accessibility regions
>94% >2 kb from TSS

Dr. Wei Tao lab Aging Cell 2021
https://onlinelibrary.wiley.com/doi/10.1111/acel.13315

AP-1 TFs also play pioneering roles in fibroblast #Senescence 🤠

AP-1 imprints a reversible transcriptional programme of senescent cells

Dr. Oliver Bischof lab Nature Cell Bio 2020
https://www.nature.com/articles/s41556-020-0529-5

SenMayo
A 125-gene set (15 studies) for #Senescence/#SASP in Bone/Bone marrow/Adipose/Brain...

#Senolytic readout

vs GenAge & CellAge

MIF as a key SASP gene!

Dr. Dominik Saul, Joshua Farr & Sundeep Khosla labs Nature Comms 2022
https://www.nature.com/articles/s41467-022-32552-1

Great review on #Invadosome🤠

Mechanisms & roles of #Podosomes & #Invadopodia

Mechano-/geometry-sensing organelles equipped with actin/microtubule/ion channels
Migration+Adhesion
Secrete MMPs/DNAase

Dr Stefan Linder & John Condeelis labs Nat Review MCB 2023
https://www.nature.com/articles/s41580-022-00530-6

Macrophage MMP12 deficiency->

⏫Alternative Complement activation
⏫Neutrophil Elastase
⏫Elastin loss
-> ⏫#AbdominalAorticAneurysm

MMP12 mainly acts more as a complement modulator (Cut C3/5?) than elastase in AAA

Dr. Mehran Sadeghi lab Circ Res 2023
https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.122.322096

Enjoy the Discussion section. Complement system is complex & charming

Fig 1F, 6D, I guess that some stainings were done on adjacent sections?🤪

BRD4 #Cardiomyocyte #Mitochondria #HeartFailure

Epigenetic Reader BRD4 (Bromodomain-Containing Protein 4) Governs Nucleus-Encoded Mitochondrial Transcriptome to Regulate Cardiac Function

A super-cool paper!

Dr. Thomas G. Gillette & Joseph Hill labs Circulation 2020
https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.047239

#Cohesinopathy

BRD4 (acetyl lysine reader)-NIPBL (cohesin loading ) complex is critical to #NeuralCrest differentiation into #SmoothMuscleCell

BRD4 depletion->⏬#GenomeFolding+loop extrusion

BRD4 in #AorticAneurysm?

Dr. Rajan Jain lab Nature Genet 2021
https://www.nature.com/articles/s41588-021-00934-8

#ArterioVenousFistula #EndMT

Low #OscillatoryShearStress->
⏫Osteopontin-CD44 in #EndothelialCell->
⏫EndMT->
⏫24% of neointimal cells at rat aortocaval junction

A cascade independent of #HyaluronicAcid🤓

Dr. Yung-Hsin Yeh lab Kidney Int 2023
https://www.kidney-international.org/article/S0085-2538(23)00011-X/fulltext