Hao Yin @HaoYin@qoto.org

Single-nuclei Transcriptomics human Lung
#COVID19 x7
IPF x6
Ctrl x12

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

Dr. Peter Carmeliet lab #CardiovascRes 2022
https://academic.oup.com/cardiovascres/advance-article/doi/10.1093/cvr/cvac139/6673943

Blood Vessel Organoids for Development & Disease

Self-organizing capillary blood vessel #Organoid #EndothelialCell+#Pericyte (+Astrocyte for #BBB)

Transplant to gain vascular hierarchy

Organotypism Through Genetic Drivers

Dr. Josef Penninger lab Circ Res 2023
https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.122.321768

Aortic #Endotheliopathy #MarfanSyndrome

En face #EndothelialCell morphometry->
Alterations in EC shape/junction/alignment/eNOS Precede aortic dilation in Marfan🐭

Flow-sensing defect?😆

Dr. Vivian de Waard lab Scientific Reports 2023
https://www.nature.com/articles/s41598-022-26662-5

Spatial Omics DataBase SODB

"a web-based platform providing both rich data resources & a suite of interactive data analytical modules" for >2700 #SpatialOmics Exps

26 spatial omics techniques

TencentAI🐧 Nature Methods 2023
https://www.nature.com/articles/s41592-023-01773-7

website:
https://gene.ai.tencent.com/SpatialOmics/

Other #SpatialOmics databases🤠

SpatialDB
http://www.spatialomics.org/SpatialDB/

STomicsDB
https://db.cngb.org/stomics/

SOAR
https://soar.fsm.northwestern.edu/

Mechano-vulnerability of #EndothelialCell in #Atherosclerosis 🤠

EVA1A, elevated by #DisturbedFlow-Twist1 axis, blocks EC #Autophagy & induces #Apoptosis

Dr. Paul Evans & Jovana Serbanovic-Canic lab ATVB 2023
https://www.ahajournals.org/doi/10.1161/ATVBAHA.122.318110

Interesting to note that LC3B in EC +72 h #DisturbedFlow is mostly lipidated (Fig. 4A)

Does this suggest that endothelium under #DisturbedFlow enter an Autophagy-dependent state? For Survival, Shear-sensing & Secretion? 🧐

#EndothelialCell #Sirt6 deficiency->
⏫#TissueFactor/F3+vascular inflammation genes Cox2, VCAM1, TNFα, MCP1
Accelerated Carotid arterial #Thrombosis (Rose bengal)

A role in atherosclerotic plaque stability?😃

Dr. Christian Matter lab JMCC 2022
https://www.jmcc-online.com/article/S0022-2828(22)00565-X/fulltext

A splendid clonal-lineage tracing study (with 9 reporter mice!)->
A very early time window e11.5-13.5 for lineage specification of mouse Lung Nkx2-1+ Alveolar epithelial progenitor

Dr. David Frank, Rajan Jain & Edward E. Morrisey labs, PNAS 2019
https://www.pnas.org/doi/10.1073/pnas.1813952116

InVADE platform
96-well scale-up AngioTube bioscaffolds

Endothelialized microchannel->
Inter-Organoid crosstalk; Metastasis

Open-well design-> easy intervention

Nice reading😋 on how to fabricate #OrganOnAChip

Dr. Milica Radisic lab Nature Protocols 2021
https://www.nature.com/articles/s41596-020-00490-1

#LaminarShear pushes VE-PTP (How?🤓) to downstream pole of #EndothelialCell, followed by endocytosis->⏫p-Tie2

Potentially explain how #DisturbedFlow⏫#VascularPermeability & #Atherosclerosis

Inhibition of VE-PTP by AKB-9785 fortifies #EndothelialBarrier & reduces Atheromas at atheroprone regions (aortic arch inner curvature, arch+intercostal bifurcations)🐭

Nice comparison of anti-leakage strategies
VE-PTP inhibition
Angpt1 activation of Tie2
Angpt2 inhibition

Dr. Donald McDonald & Dietmar Vestweber labs EMBO Mol Med 2023
https://www.embopress.org/doi/

Bi-allelic Emilin 1 LOF causes #Aortopathy

EMILIN1 deficiency👤🐭->
⏬Fibulin 4
⏬LOX
⏫#TGFβ signals
⏬#Elastogenesis
⏬#CollagenFibrillogenesis

Pediatric #AscendingAorticAneurysm

Dr. Gerhard Sengle & Bert Callewaert labs Am J Hum Genet 2022
https://www.cell.com/ajhg/fulltext/S0002-9297(22)00458-X

COMMOT, COMMunication analysis by Optimal Transport, a versatile tool infer cell–cell communication in #SpatialTranscriptomics 🤠

Compatible with #MERFISH #Visium seqFISH+ #STARmap

vs #CellChat #Giotto #CellPhoneDBv3

Dr. Qing Nie lab Nature Methods 2023
https://www.nature.com/articles/s41592-022-01728-4

"Division of Labor" in Lung endothelial host defense 🐭#Endotoxemia 🐭#Influenza🐵#SARSCOV2

2 subsets of🫁general capillary #EndothelialCell
Irf7+ immune EC
Sox17+ developmental (regenerative) EC

Dr. Jalees Rehman lab JCI Insight 2022
https://insight.jci.org/articles/view/158079

#HutchinsonGilfordProgeriaSyndrome #Aorta

Material & Structural #Biomechanics of large arteries of #Progeria🐭LmnaC609G/C609G

Crucial insights into regionalized mechano-vulnerability of elastic arteries in #Progeria

Dr. Jay Humphrey lab bioRxiv 2023
https://www.biorxiv.org/content/10.1101/2023.01.10.523266v1.full

Use Organoid to study Plasticity & Organotypic traits of #EndothelialCell

3D Cardiac Microtissue
#hiPSC-cardiomyocyte, -Fibroblast, -EC

scRNAseq
hiPSC-cardiac mesoderm-EC vs
hiPSC-Paraxial mesoderm-EC
in🫀Organoid

Dr. Valeria Orlova lab bioRxiv 2022
https://www.biorxiv.org/content/10.1101/2022.11.22.517426v2.full

#Autophagy #Mechanobiology

#CyclicStretch 10% 1.25Hz->
Microtubule depolymerization in venous SMC->
⏬autophagosome-lysosome fusion->
⏫p62 aggregate, binding to KEAP1->
⏫NRF2 antioxidant pathway->
⏫Vein Graft Stenosis

Dr. Ying-Xin Qi lab JMCC 2022
https://www.jmcc-online.com/article/S0022-2828(22)00534-X/fulltext

Learn RNAseq #BatchCorrection, find this powerful paper🤠 (though mine is not scRNAseq)

A benchmark of batch-effect correction methods for single-cell RNA sequencing data

14 methods; 9 datasets

Dr. Jinmiao Chen Genome Biology 2020
https://genomebiology.biomedcentral.com/articles/10.1186/s13059-019-1850-9

Striking Pulmomary #Vasculitis in #COVID19
3 case+2 Ctrl
Thickened+Broken elastin in hyalinizing arterial wall😎

Thbs1-hi CD163+ non-canonical Monocyte in fatal COVID! To activate platelet only?🧐
Dr. Kiyoshi Hirahara & Toshinori Nakayama labs PNAS 2022
https://www.pnas.org/doi/10.1073/pnas.2203437119

Plasma MYL9 level corr. with COVID severity!

And look at these crazy MYL9/12+ thrombi in small pulmonary arteries😬

What's the role of MYL9, a #SmoothMuscleCell contractile protein, in platelets?

This leads me into another wonderland (🐰hole)

Platelet-deposited MYL9/12 as Luminal scaffold guiding T-cell migration!?😈

Dr. Toshinori Nakayama lab Sci Immunology 2016
https://www.science.org/doi/10.1126/sciimmunol.aaf9154

Another intriguing paper on leukocyte vs arterial mural cell-derived MYL9/12 & #Vasculitis 😆

Increased Myosin light chain 9 expression during #KawasakiDisease Vasculitis

Dr. Motoko Kimura & Hiromichi Hamada labs Front Immunol 2022
https://www.frontiersin.org/articles/10.3389/fimmu.2022.1036672/full

#Monocyte deposits VEGF/CXCL12-containing #Migrasome to stimulate CAM #Angiogenesis, as well as reinforce monocyte recruitment

Wonder if this fascinating cascade is also functional in tissue regeneration?😆

Dr. Li Yu lab Nature Cell Bio 2022
https://www.nature.com/articles/s41556-022-01026-3

Happy to report our review in Current Atherosclerosis Reports!

#Telomere Length: Implications for Atherogenesis

by me & my supervisor Dr. J. Geoffrey Pickering

TL as a biomarker & causal factor for ASCVD
Evidence from seminal studies, incld #UKBiobank #TOPMed
https://link.springer.com/article/10.1007/s11883-023-01082-6

In vitro systems to study endothelial/pericyte cell interactions

Hydrogel
Collgen/Matrigel/PEG

#Microfluidic #VesselOnAChip

Engineering microvessels

Blood vessel #Organoid
BBB organoid

Dr. Emily Warren & Sharon Gerecht Vascular Biology 2023
https://vb.bioscientifica.com/view/journals/vb/aop/vb-22-0021/vb-22-0021.xml