Hao Yin @HaoYin@qoto.org

Human Serine/Threonine #Kinome👍
303 kinases

Substrate Motif Atlas->
Annotation of Human Ser/Thr phosphoproteome
Novel substrates+signaling roles of kinases

Dr Benjamin Turk, Michael Yaffe & Lewis Cantley labs @Nature 2023
https://www.nature.com/articles/s41586-022-05575-3

#Senescence of Skeletal Myofiber with #Aging

p21, Lipofuscin, HMGB1, TAF, lamin B1 variance

Senescent myofibers are small + more central nuclei

Transplanted senescent fibroblasts->local #BystanderSenescence

Dr. Thomas Von Zglinicki lab Aging Cell 2018
https://onlinelibrary.wiley.com/doi/10.1111/acel.12848

De Novo pathogenic variant of miR-145-5p (het?😃) in #MultisystemSmoothMuscleDysfunctionSyndrome #RareDisease

+mRNA & miR transcriptomes of patient skin fibroblast-/+TGFβ1 😋

Dr Mark Lindsay lab JCI 2023
@MarkELindsay
@markelindsay
https://www.jci.org/articles/view/166497

miR-145-5p is a master miRNA to maintain #SmoothMuscleCell contractile phenotype

My favorite among the earliest miR-145 papers👇

Acquisition of the contractile phenotype by murine arterial SMCs depends on the Mir143/145 gene cluster

JCI 2009
https://www.jci.org/articles/view/38864
=====

miR-145
CARMN
SMILR
...

The (re-)arising of smooth muscle-enriched non-coding RNAs makes me really nostalgic for my PhD days & nights😸 in Calgary

Marvelous #IntussusceptiveAngiogenesis encasing alveoli in mice with compensatory post-pneumonectomy growth🤩

Corrosion cast+SEM

Synchrotron radiation-based tomographic microscopy

Dr. Moritz Konerding lab Angiogenesis 2014
https://link.springer.com/article/10.1007/s10456-013-9399-9

Partial #EndMT,⏫by #Hypoxia-induced CD45, as a major cellular source for neointima formation

50% ECs in ligated artery are CD45+

CD45 is required to maintain this Partial status
Amazing!🤩

Dr. Yoshito Yamashiro & Yoshito Yamashiro lab #CardiovascRes 2022
https://academic.oup.com/cardiovascres/advance-article/doi/10.1093/cvr/cvac190/6942105

How CD45 titrates the extent of mesenchymalization of #EndothelialCell?

CD45 stabilizes VE-cad junction via fortifying integrin α11-SHARPIN complex

Very interesting data on Biomechanics of #EndMT 😋

What (beyond CD45) control partial-to-complete EndMT transition?🤓

#Heme biosynthesis #Angigoenesis

Roles of #EndothelialCell FLVCR1a, a heme exporter to extracellular space in
✅Developmental Angiogenesis-🐭Retina🐟ISV
✅Tumor angiogenesis
❎Vascular homeostasis

Dr. Sara Petrillo lab Angiogenesis 2023
https://link.springer.com/article/10.1007/s10456-023-09865-w

FLVCR1a deficiency-> #EndothelialCell-autonomous defects in Mitochondria, ER stress & Angiogenic behaviors

Heme accumulation triggers #Paraptosis (Organelle swelling-> Cytoplasic vacuolation)💀

Dr. Emanuela Tolosano lab Cell Death Diff 2018
https://www.nature.com/articles/s41418-017-0001-7

Other enzymes in Heme metabolism in #Angiogensis👇

Ferrochelatase is a therapeutic target for ocular neovascularization
https://www.embopress.org/doi/full/10.15252/emmm.201606561

Serine Synthesis via PHGDH Is Essential for Heme Production in Endothelial Cells
https://www.cell.com/cell-metabolism/fulltext/S1550-4131(18)30391-7

Spatial analysis of Lung microvascular damage+regeneration, correlated with zoned alveolar damage following #Influenza injury

A critical role of #EndothelialCell COUP-TF2/Nr2f2
-Transcriptionally⏫CyclinD1+NRP1
-⏬by NFκB

Dr. Andrew Vaughan lab @vaughandy Science Advances 2020
https://www.science.org/doi/10.1126/sciadv.abc4493

What an eye-opening review!👏

Metabolites as signalling molecules

Absolutely a must-read for biology researchers

Dr. Steven Andrew Baker & Jared Rutter Nature Reviews Molecular Cell Biology 2023
https://www.nature.com/articles/s41580-022-00572-w

For the #Angiogenesis lovers, read this great #AngioMetabolite story

Endothelial Lactate Controls Muscle Regeneration from Ischemia by Inducing M2-like Mφ Polarization

EC in hypoxic muscle is a major resource of Lactate!

Dr. Katrien de Bock @cell_metabolism
2020
https://www.sciencedirect.com/science/article/pii/S1550413120302436

So hard to keep updated with the literature, even review🤖

Perhaps need to ask #ChatGPT to how to strategize my reading......

3D #Bioprinting of #OuterBloodRetinaBarrier #RetinalPigmentEpithelium + #Choriocapillaris

#hiPSC-RPE/EC/pericyte/fibroblast
PLGA nanoscaffold
Fibrin-gelatin

Modeling Dry & Wet #AMD🤠

RPE⏫Capillary Fenestration👈😎

Dr. Kapil Bharti lab Nature Methods 2022
https://www.nature.com/articles/s41592-022-01701-1

#ThoracicAorticAneurysm
#EndothelialCell-#SmoothMuscleCell Synergy

EC Fbln4 KO exacerbates Aortopathy of SMC Fbln4 KO
-Aneurysm into Arch
-Descending Aortic tortuosity
-Postnatal aortic valve thickening/#EndMT

Dr. Yoshito Yamashiro and Hiromi Yanagisawa labs JAHA2022
https://www.ahajournals.org/doi/10.1161/JAHA.122.026942

#Osteocyte Remodeling of the #LacunarCanalicularSystem: What’s in a Name?

How do Osteocyte & osteogenic lineages assemble mineral & organic/collagenous matrix into such an exquisite lumenized network🤩

Dr. C. M. Heveran & J. D. Boerckel Curr Osteoporos Rep 2022
https://link.springer.com/article/10.1007/s11914-022-00766-3

Follow-up with an interesting paper on #Aging-related human #Osteocyte Lacunae remodeling

Bone biopsy 109👤 1.5-95 yr

Lacunae morphometry + #Micropetrosis (highly mineralized lacunae) by #BackscatteredElectronImaging

Dr Stéphane Blouin lab @ActaBio 2022
https://www.sciencedirect.com/science/article/pii/S1742706122007826

Tie2+ #EndothelialCell Egln1/PHD2 KO mice
->Spontaneous #PulmonaryArterialHypertension as early as 1.5 mo

A cascade of EC PHD2 KO->
⏫autocrine #CXCL12->
⏫FoxM1-dependent proliferation

Dr. Zhiyu Dai lab IJMS_MDPI 2021
https://www.mdpi.com/1422-0067/22/6/3182

Also read Dr. Dai Circulation 2016🤠presenting EC PHD2 KO, causing PAH via HIF2α (not HIF1α)

PHD2 Deficiency in Endothelial Cells & Hematopoietic Cells Induces Obliterative Vascular Remodeling & Severe Pulmonary Arterial Hypertension PAH in🐭👤Through HIF2α
https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.116.021494

Hallmarks of #Aging: An expanding universe🤖

Genomic instability
Telomere
Epigenetics
Proteostasis
Macroautophagy
Nutrient-sensing
Mitochondria
Senescence
Inflammation
Dysbiosis
etc

Dr. Carlos López-Otín, Guido Kroemer & colleagues @cellpress 2023
https://www.sciencedirect.com/science/article/pii/S0092867422013770

Endotheliopathy #CysticFibrosis

CFTR-deficient #EndothelialCell
⏫Inflammation IL8/SELE/ICAM1/VCAM1
⏬Proliferation
⏬Autophagy
⏬Barrier
⏫Mitochodriopathy

Dr. Lucas Treps, Guy Eelen, Peter Witters labs Eur Respir J 2021
https://erj.ersjournals.com/content/57/4/2000261.long

#Angiocrine #AlveolarRegeneration

P.aeruginosa Lung injury,🐭#EndothelialCell KO of Sphk1, S1P-generating enzyme->
Excess Sftpc-hi AT2
AT1 loss & airspace enlargement

S1P/S1PR2⏫#YAP nucleation->⏫AT2-to-AT1 differentiation

Dr. Yuru Liu lab Cell Reports 2020
https://www.sciencedirect.com/science/article/pii/S2211124720308093

The relation of aortic Diameter/Length & #Obesity in #Marfan (n=27) or #LoeysDietzsyndrome (n=7) adults

Whole aortic length 504±59 mm
Thoracic-> 352±52 mm
Abdominal-> 153±27 mm
Tortuosity? vs healthy?🧐

Dr. Mathieu Suleiman lab Cardiovasc Diagn Ther 2022
https://cdt.amegroups.com/article/view/106535/html

A remarkable mechanism for #DisturbedFlow disruption of #EndothelialCell Junction in #Atherosclerosis

Disturbed Flow-activated GRK2 phosphorylates #Vinculin Ser721-> a closed conformation of Vinculin
->⏬VE-cad junction

Dr. Jeng-Jiann Chiu lab Euro Heart J 2022
https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehac647/6830649

#AorticValve Fenestration
260 donors 61 yr
43% with valvular fenestration, present in all 3 leaflets
Size of fenestration⏫with Age (r=0.31)
>95% located at the free edges of leaflets in commissural areas

Dr. Mateusz Hołda lab Clin Anat 2023
https://onlinelibrary.wiley.com/doi/10.1002/ca.24002

CXCL12/SDF-1 in Lung #EndothelialCell #BranchingMorphogenesis

CXCL12 KO->
Vaso-Hypoplasia
⏫Arterial branches
⏬Arterialɸ
⏬Artery+Capillary density

Any alterations in Airway branching & Alveologenesis?😋

Important to note that even lung capillary ECs are labeled by CXCL12-DsRed

Though EC is a major CXCL12 source in developing mouse lung, EC CXCL12 KO only has a minor vascular defect on primary branches

Dr. Jennifer Sucre & David Frank lab @Dev_journal 2022
https://journals.biologists.com/dev/article/149/21/dev200909/278588/CXCL12-defines-lung-endothelial-heterogeneity-and

Lung Alveolar Capillary #EndothelialCell Specification #EvoDevo

Plvap+Gpihbp1+Aplnr+Cxcl12+ General capillary EC
Car4+Ednrb+Fibin+Apln+Chst1+ #Aerocyte

❎🐊🐢 Faveoli
✅🐭👤 Alveoli

A beautiful study🤩

Dr. Mark Krasnow & Ross Metzger labs Nature 2020
https://www.nature.com/articles/s41586-020-2822-7