#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

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

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

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