Hao Yin @HaoYin@qoto.org

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

Fantastic story
AT1-#EndothelialCell crosstalk in Lung #Alveologenesis🤠

Hopx+ AT1 Vegfa KO->
Loss of Car4+ EC ramifying over Alveoli
w/o reduced PLVAP+ capillary EC->
Alveolar Smoothening (⏬Outpocketing?)🧐

Dr. Jichao Chen lab Dev Cell 2020
https://www.cell.com/developmental-cell/fulltext/S1534-5807(20)30010-1

Arterial dissections: Common features and new perspectives

A comprehensive review covering diverse arterial beds

Biomechanics
#EndothelialCell+#SmoothMuscleCell plasticity
Genetics
TGFβ, ECM

Dr. Robert Graham lab Frontiers Cardiovascular Medicine 2022
https://www.frontiersin.org/articles/10.3389/fcvm.2022.1055862/full

Mouse Lung Spliceomic e15.5-P8

Enriched pathways Junctions; Hippo

Novel VEGFA splice variant
VEGFA i5😎

AT1 as a major lung cell for VEGFA expression & alternative splicing

VEGFA-188 (not -164) promote Car4+#Aerocyte specification

Dr. Francisca Vasconcelos & Cláudio Franco labs, Life Science Alliance 2022
https://www.life-science-alliance.org/content/5/12/e202201554

Lung #EndothelialCell Heterogeneity & Proliferation post H1N1 #Influenza injury

EC subpopulation 14 dpi trajectory (Slingshot)
Ligand-receptor analysis (FANTOM5)->
AT1-to-Car4-hi EC signaling in #AlveolarRegeneration

Dr. Edward E Morrisey lab @eLife 2020
https://elifesciences.org/articles/53072

Stabilizing FOXF1 to treat #AlveolarCapillaryDysplasia

Chemical screening->TanFe
⏬Ubiquitination of FOXF1 via⏬binding to #E3Ligase HECTD1/SHPRH/NEURL1B etc->

Restoring Lung #Angiogenesis of Foxf1+/-🐭

Dr. Vladimir Kalinichenko lab Am J Respir Crit Care Med 2022
https://www.atsjournals.org/doi/10.1164/rccm.202207-1332OC

How FOXF1 impacts #EndothelialCell #Angiogenesis?

As a transcription factor for S1PR1 & VE-Cad😎

An excellent story from Dr. Vladimir Kalinichenko lab @scisignal 2016👇

FOXF1 maintains endothelial barrier function and prevents edema after lung injury

https://www.science.org/doi/10.1126/scisignal.aad1899

Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins, due to FOXF1 heterozygous mutation, has very complex Lung & ex-Lung vascular phenotypes

A few reads🤠

https://diagnosticpathology.biomedcentral.com/articles/10.1186/s13000-020-00972-6

https://www.nature.com/articles/jp201494

https://www.nature.com/articles/ejhg2012171

https://www.jpeds.com/article/S0022-3476(04)00647-X/fulltext

Aberrant Mechanical tension-activated TGFβ1-SMAD2/3 signaling, synergized with Cdc42 deficiency, in AT2 alveolar cells causes peripheral-to-center progression #PulmonaryFibrosis in🐭post-lung lobe resection

Dr. Jingyu Chen & Nan Tang labs @cellpress 2019
https://www.cell.com/cell/fulltext/S0092-8674(19)31284-X

Interesting, ablation of TGFβR2 in Cdc42 KO AT2 cells blunts fibrotic expansion w/o rescuing #AlveolarRegeneration

In contrast, Normalizing the ectopic mechanical tension post-lung lobe resection, using a unique silicon prosthesis, rescues both alveolar regeneration & fibrosis

How Cdc42 controls AT2 cell mechanosensitivity & plasticity during #AlveolarRegeneration?

A Cdc42-F-actin-JNK/p38-YAP cascade

A very cool paper🤠👇

Dr. Nan Tang lab @CellReports 2016
https://www.cell.com/cell-reports/fulltext/S2211-1247(16)30919-6

Single-cell Transcriptomic Atlas of human Lung

75k cells
58 molecular types: 15 epithelial, 9 endothelial, 9 stromal, 25 immune
7 tissue blocks
1♀️+2♂️

17/58👤molecular types absent in🐭 Lung

Dr. Stephen Quake & Mark Krasnow labs @Nature 2020
https://www.nature.com/articles/s41586-020-2922-4

AT1 cell Plasticity in #Alveologenesis & Lung Homestasis+Regeneration

AT1 contributes to 30% & 10% AT2 in neonatal & adult 🐭Hyperoxia Lung injury👹

TAZ (likely > #YAP) maintains adult AT1 lineage identity Fig 6E

Dr. David Frank & Edward Morrisey Labs @CellStemCell 2021
https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(21)00184-3

Vinculin-α-Catenin complex⏫#EndothelialCell Barrier during vascular morphogenesis

Vinculin a/b deficient🐟 48hpf->
Enhanced Permeability of 10 kD (not 70 kD) dextran of DLAV & ISV, but not dorsal aorta

Dr. Stephan Huveneers lab Vascular Biology 2022
https://vb.bioscientifica.com/view/journals/vb/aop/vb-22-0012/vb-22-0012.xml

Causal role of #Endotheliopathy in #Emphysema #COPD 🤠

i.v. Delivery of E4ORF1-transduced Lung #EndothelialCell
Or EC LRG1 (TGFβ/Alk1/Eng modulator) KO
alleviates elastase-induced🐭COPD

Dr. Alexandra Racanelli, Shahin Rafii & Augustine Choi labs J Exp Med 2021
https://rupress.org/jem/article-standard/218/8/e20200938/212491/Reversal-of-emphysema-by-restoration-of-pulmonary

Damage-associated transient progenitor in #AlveolarRegeneration

Lung Organoid+ multi reporter🐭->
Lineage trajectory of AT2 cells of bleomycin lung injury🤠

ILβ-primed AT2->
Cldn4+Ndrg1+Krt8+Ly6a+ bipotent DATP->
AT1

Dr. Joo-Hyeon LeeLab @CellStemCell 2020
https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30287-3

ATF3+ lung capillary #EndothelialCell proliferates & promotes #AlveolarRegeneration post H1N1 injury #Flu

🫁ATF3 KO EC 14 dpi->
⏬Proliferation
⏫Apoptosis
Altered Angiogcrine🤠🧐 to⏬AT1+AT2 epithelial cells

Dr. Edward E. Morrisey lab bioRxiv 2022
https://www.biorxiv.org/content/10.1101/2022.10.14.512212v1.full

Reminiscent of the really cool work from Dr. Katrien De Bock @cell_metabolism 2021

#SkeletalMuscle ATF3/4+ Capillary #EndothelialCell, preferably surrounding oxidative myofibers, as a major cellular origin of Exercise-induced #Angiogenesis😎

https://www.sciencedirect.com/science/article/pii/S1550413121003314