Effects of 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
nature.com/articles/s41580-021

====

Any evidence on in cardiovascular biology?

From Abraham Aviv lab @ATHjournal 2001

Age-dependent aneuploidy & telomere length of the human vascular endothelium
atherosclerosis-journal.com/ar

Tetrasomy Chr6 Chr16
Loss ChrY

Aneuploidy in cardiovascular diseases?🧐

====

Mice with 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
ahajournals.org/doi/10.1161/01

=======
Vascular BubR1 2/3

BubR1 Insufficiency Inhibits Through Impaired Vascular Proliferation in Mice

Dr. Takuya Matsumoto lab @atvbahajournals 2014
ahajournals.org/doi/10.1161/AT
====

Vascular BubR1 3/3

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

Dr. Takuya Matsumoto lab @JVascSurg 2018
jvascsurg.org/article/S0741-52

CRISPR-activated Oct4 as for (LmnaC698G) & natural aged🐭

Polyethylenimine-cationic gold nanoparticle iv.

Do we need an aortotropic vector for ?

Dr. Jongpil Kim lab @AgingCell 2023
onlinelibrary.wiley.com/doi/10

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 in

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

Dr. Stuart A Cook & Wei Wen Lim lab ATVB 2023
ahajournals.org/doi/10.1161/AT

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

ahajournals.org/doi/10.1161/CI

Epigenetics

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

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

Dr H Zhao lab Cell Death Discovery 2023
nature.com/articles/s41420-023

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

Geometry
Velocity
Hematocrit
Viscosity

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

Dr. Li-Kun Phng lab Front Physiol 2022
frontiersin.org/articles/10.33

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"

in vascular morphogenesis

Human Meniscus single-cell RNAseq atlas
4 normal+4

5 subtypes
Emerging proliferative chondrocyte in degenerated tissue

OA-related /#MuralCell-Chondrocyte crosstalks🤓

Dr. W Fu & X Zhang labs @eLife 2023
elifesciences.org/articles/795

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

Sertoli, Not SCF->
maintenance+differentiation

Cell-specific SCF Glycosylation? Proximity?🧐

Dr Hongfang Shao, Bo Zhou lab @Dev_journal 2023
journals.biologists.com/dev/ar

A highly intriguing --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
biorxiv.org/content/10.1101/20

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
frontiersin.org/articles/10.33

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

MERFISH+scRNAseq 10 M+ cells

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

Dr. Hongkui Zeng lab BioRxiv 2023
biorxiv.org/content/10.1101/20

A methodological frame to optimize antibody staining of -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
elifesciences.org/articles/841

deacetylates & ->
⏬their transcriptional activities
⏬TGFβ1-induced Fibrotic reprogramming of
in diet-induced🐭

TAZ seems more sensitive to Sirt6 than YAP🤓

Dr. Charlie Dong lab FASEB J 2022
faseb.onlinelibrary.wiley.com/

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

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

Dr. Wei Tao lab Aging Cell 2021
onlinelibrary.wiley.com/doi/10

AP-1 TFs also play pioneering roles in fibroblast 🤠

AP-1 imprints a reversible transcriptional programme of senescent cells

Dr. Oliver Bischof lab Nature Cell Bio 2020
nature.com/articles/s41556-020

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

readout

vs GenAge & CellAge

MIF as a key SASP gene!

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

Great review on 🤠

Mechanisms & roles of &

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
nature.com/articles/s41580-022

Macrophage MMP12 deficiency->

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

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

Dr. Mehran Sadeghi lab Circ Res 2023
ahajournals.org/doi/10.1161/CI

Enjoy the Discussion section. Complement system is complex & charming

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

BRD4

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
ahajournals.org/doi/10.1161/CI

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

BRD4 depletion->⏬+loop extrusion

BRD4 in ?

Dr. Rajan Jain lab Nature Genet 2021
nature.com/articles/s41588-021

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

A cascade independent of 🤓

Dr. Yung-Hsin Yeh lab Kidney Int 2023
kidney-international.org/artic

Single-nuclei Transcriptomics human Lung
x7
IPF x6
Ctrl x12

COVID🫁
⏫Systemic venous+capillary
⏬general capillary EC
⏬Epi-Endo Notch, EC-stromal PDGF
⏫Stromal-EC PlxnA-Sema3A

Dr. Peter Carmeliet lab 2022
academic.oup.com/cardiovascres

Blood Vessel Organoids for Development & Disease

Self-organizing capillary blood vessel + (+Astrocyte for )

Transplant to gain vascular hierarchy

Organotypism Through Genetic Drivers

Dr. Josef Penninger lab Circ Res 2023
ahajournals.org/doi/10.1161/CI

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