Big Congrats 🎉 to Rui Li & collaborators from the lab of Stefan Offermanns at @mpi_hlr
for this great #NatureComms paper showing that FAT1 controls YAP/TAZ degradation via the E3 ligase MIB2 during #angiogenesis.
Happy of my small contribution!
https://doi.org/10.1038/s41467-023-37671-x
IL-11 as a therapeutic target for lung #Fibrosis #Emphysema in #MarfanSyndrome
In Marfan🐭🫁, IL11-GFP reporter is active in #EndothelialCell #SmoothMuscleCell Fibroblast but not alveolar epithelia
Dr. Stuart A Cook & Wei Wen Lim lab ATVB 2023
https://www.ahajournals.org/doi/10.1161/ATVBAHA.122.318802
Also don't miss the story on IL-11 as mediator of Mafan #Aortopathy from Circ Res 2022
https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.121.320381
Human Meniscus single-cell RNAseq atlas
4 normal+4 #OsteoArthritis
5 #Chondroncyte subtypes
Emerging proliferative chondrocyte in degenerated tissue
OA-related #EndothelialCell/#MuralCell-Chondrocyte crosstalks🤓
Dr. W Fu & X Zhang labs @eLife 2023
https://elifesciences.org/articles/79585
A single-cell transcriptome atlas reveals meniscal microenvironment variations during degeneration and cellular heterogeneity foundations of the inner–outer zone differences, suggesting novel cell subtypes as potential therapeutic targets.
Amh+ #SertoliCell is a major (80%) cellular source of #StemCellFactor in🐭Testis
Sertoli, Not #EndothelialCell SCF->
#Spermatogonia maintenance+differentiation
Cell-specific SCF Glycosylation? Proximity?🧐
Dr Hongfang Shao, Bo Zhou lab @Dev_journal 2023
https://journals.biologists.com/dev/article/doi/10.1242/dev.200706/293491/Sertoli-cells-are-the-unique-source-of-stem-cell
Several cell types have been proposed to create the microenvironment for spermatogenesis. However, the expression patterns of the key growth factors produced by these somatic cells have not been systematically studied and no such factor has been conditionally deleted from its primary source(s), raising the question of which cell type(s) are the physiological sources of these growth factors. Here, using single-cell RNA sequencing and a series of fluorescent reporter mice, we found that, Stem cell factor (Scf), one of the essential growth factors for spermatogenesis, was broadly expressed in testicular stromal cells, including Sertoli, endothelial, Leydig, smooth muscle cells and Tcf21-CreER+ stromal cells. Both undifferentiated and differentiating spermatogonia were associated with SCF-expressing Sertoli cells in the seminiferous tubule. Conditional deletion of Scf from Sertoli cells, but not any other SCF-expressing cells, blocked the differentiation of spermatogonia, leading to complete male infertility. Conditional overexpression of Scf in Sertoli cells, but not endothelial cells, significantly increased spermatogenesis. Our data revealed the importance of anatomical localization for Sertoli cells in regulating spermatogenesis. Sertoli cells are the unique source of SCF that is essential for spermatogenesis.
AP-1 transcription factors ATF3/FOSL1/FOSL2/c-JUN reshape Chromatin Accessibility landscape during #EndothelialCell #Senescence
HUVEC PD 8vs24vs36
1038 & 964 increased & decreased accessibility regions
>94% >2 kb from TSS
Dr. Wei Tao lab Aging Cell 2021
https://onlinelibrary.wiley.com/doi/10.1111/acel.13315
AP-1 TFs also play pioneering roles in fibroblast #Senescence 🤠
AP-1 imprints a reversible transcriptional programme of senescent cells
Dr. Oliver Bischof lab Nature Cell Bio 2020
https://www.nature.com/articles/s41556-020-0529-5
Low #OscillatoryShearStress->
⏫Osteopontin-CD44 in #EndothelialCell->
⏫EndMT->
⏫24% of neointimal cells at rat aortocaval junction
A cascade independent of #HyaluronicAcid🤓
Dr. Yung-Hsin Yeh lab Kidney Int 2023
https://www.kidney-international.org/article/S0085-2538(23)00011-X/fulltext
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
Patients with Marfan syndrome (MFS) develop thoracic aortic aneurysms as the aorta presents excessive elastin breaks, fibrosis, and vascular smooth muscle cell (vSMC) death due to mutations in the FBN1 gene. Despite elaborate vSMC to aortic endothelial cell (EC) signaling, the contribution of ECs to the development of aortic pathology remains largely unresolved. The aim of this study is to investigate the EC properties in Fbn1C1041G/+ MFS mice. Using en face immunofluorescence confocal microscopy, we showed that EC alignment with blood flow was reduced, EC roundness was increased, individual EC surface area was larger, and EC junctional linearity was decreased in aortae of Fbn1C1041G/+ MFS mice. This modified EC phenotype was most prominent in the ascending aorta and occurred before aortic dilatation. To reverse EC morphology, we performed treatment with resveratrol. This restored EC blood flow alignment, junctional linearity, phospho-eNOS expression, and improved the structural integrity of the internal elastic lamina of Fbn1C1041G/+ mice. In conclusion, these experiments identify the involvement of ECs and underlying internal elastic lamina in MFS aortic pathology, which could act as potential target for future MFS pharmacotherapies.
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? 🧐
Francoise Helmbacher
Hao Yin