Hao Yin @HaoYin@qoto.org

#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

Local implant of #BMP2-loaded GelMA hydrogel improves #Osteogenesis+#Angigoenesis in rat critical-size Mandibular defect

⏫type H CD31+Emcn+ vessel
⏫Perivascular Osx+ osteoprogenitor
⏫CD51+ #SkeletalStemCell

Dr. L. Qin & J. Xu labs Pharmaceutics 2022
https://www.mdpi.com/1999-4923/14/11/2397

#LoeysDietzSyndrome Bone phenotypes

SMAD3 p.I67S->
⏬ SMAD3 protein stability & TGFβ signals
⏬ Cortical+trabecular width + Mineralization
Normal osteoid volume

One patient, transiliac bone biopsy, vs reference values

Dr. Wolfgang Högler lab Bone Rep 2022
https://www.sciencedirect.com/science/article/pii/S2352187222004375

Targeting #EndothelialCell CXCR7(Up) or Jag1(Down) to untangle the vicious feed-forward loop b/w EC &
perivascular Macrophage driving #PulmonaryFibrosis
Mice with repeated lung injury by Bleomycin/HCl

Dr. Zhongwei Cao, Shahin Rafii & Bi-Sen Ding labs Nature Medicine 2016
https://www.nature.com/articles/nm.4035

Repeated chemical Lung injury suppresses EC CXCR7 & recruits PlGF-responsive VEGFR1+ Macrophage

Macrophage-derived Wnt3->?EC beta Catenin-Jag1-> subsequent Notch+ fibroblast expansion

This cascade is otherwise depressed in EC with normal CXCR7 level upon single injury

Can't imaging this can be elucidated in one paper😆

#EndothelialCell transcriptomic atlas of human Lung

Meta-analysis of scRNAseq datasets
6 healthy human lung studies >15k ECs, 73 subjects

Love the writing. Re-learn A-C-V zonation featuring marker gene annotation👍

Dr. Naftali Kaminski lab Circulation 2021
https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.052318

Based on this important study, human lung aerocyte & general capillary EC are not best
distinguished by Car4/Apln & PLVAP/Aplnr, like in mice ??

Aerocyte: HPGD, SOSTDC1, EDNRB, TBX2
General: capillary EC: FCN3, GPIHBP1, BTNL8/9, IL7R

Also see comparative meta-analysis of mouse lung EC, 6 cohorts

Ligand-receptor connectome identify lung arterial EC as the champion secretory EC: Notch ligands, Ephrin B2, Endothelin 1, CXCL12, DKK2!

The runner-up is lymphatic EC: PDGFA, Sema3a, CCL21

A highly useful Lung cell atlas. Lots of fun

Human Lung capillary ECs are also abundant in Periaxin. Are they uptaking surfactant in lung, as myelin in brain? Or a role of Periaxin in #BloodGasBarrier?

http://www.lungendothelialcellatlas.com/

Intranasal Transplantation of 900k freshly isolated AT2 alveolar cells
⏫Lung regeneration w/o Krt5+ dysplasia, following injuries by influenza/HCl/Bleomycin, Not S. pneumonia

Dr. Andrew Vaughan lab, NPJ Regen Med 2019
https://www.nature.com/articles/s41536-019-0080-9

#Angiocrine Lung #Alveologenesis

Cyp26b1, catabolizing #RetinoicAcid, is #EndothelialCell-restricted in 🐭 emb Lung+Kidney

Cyp26b1 KO->
⏬AT1 fate of Sox9+ distal airway epithelial progenitors
⏫septa thickness
⏬Airspace

@ondinecleaver2022 @Dev_journal 2020
https://journals.biologists.com/dev/article/147/4/dev181560/223218/Cyp26b1-is-an-essential-regulator-of-distal-airway

Thoracic #AorticDissection (type A+B) in Nova Scotia, Canada🇨🇦2005-2015

382 scheduled thoracic #AorticAneurysm repair
294♂️vs 88♀️

345 dissection events
212♂️vs 133♀️
4.4 vs 2.4 per 10,000 person-years🧐

Dr. Claudia Cote lab #CJCOpen 2022
https://www.cjcopen.ca/article/S2589-790X(22)00176-7/fulltext

Crosstalk signaling b/w alveoli & capillaries

A very nice synthesis😎of pre-2018 seminar studies on bidirectional alveolar epithelial-endothelial communications in Lung development/injury/regeneration

Dr. Rebecca Hough lab, Pulmonary Circulation 2018
https://journals.sagepub.com/doi/full/10.1177/2045894018783735