Skin wound analysis from Sox9 conditional knock-out mice demonstrates a significant reduction in pathological EndMT resulting in reduced scar area. The converse was observed with Rbpj conditionally knocked-out from the murine vasculature or inhibition of Notch signaling in human endothelial colony forming cells, resulting in enhanced Sox9 and EndMT related gene
[Nature Communications]
6445218
{6445218:ZEFT6DBL}
apa
50
1
162025
https://www.stemcellsciencenews.com/wp-content/plugins/zotpress/
%7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3A%22zotpress-788cb380b2f38e33d2800244bf1c184e%22%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%22ZEFT6DBL%22%2C%22library%22%3A%7B%22id%22%3A6445218%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Zhao%20et%20al.%22%2C%22parsedDate%22%3A%222021-05-07%22%2C%22numChildren%22%3A2%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EZhao%2C%20J.%2C%20Patel%2C%20J.%2C%20Kaur%2C%20S.%2C%20Sim%2C%20S.-L.%2C%20Wong%2C%20H.%20Y.%2C%20Styke%2C%20C.%2C%20Hogan%2C%20I.%2C%20Kahler%2C%20S.%2C%20Hamilton%2C%20H.%2C%20Wadlow%2C%20R.%2C%20Dight%2C%20J.%2C%20Hashemi%2C%20G.%2C%20Sormani%2C%20L.%2C%20Roy%2C%20E.%2C%20Yoder%2C%20M.%20C.%2C%20Francois%2C%20M.%2C%20%26amp%3B%20Khosrotehrani%2C%20K.%20%282021%29.%20Sox9%20and%20Rbpj%20differentially%20regulate%20endothelial%20to%20mesenchymal%20transition%20and%20wound%20scarring%20in%20murine%20endovascular%20progenitors.%20%3Ci%3ENature%20Communications%3C%5C%2Fi%3E%2C%20%3Ci%3E12%3C%5C%2Fi%3E%281%29%2C%202564.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41467-021-22717-9%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41467-021-22717-9%3C%5C%2Fa%3E%20%3Ca%20title%3D%27Cite%20in%20RIS%20Format%27%20class%3D%27zp-CiteRIS%27%20href%3D%27https%3A%5C%2F%5C%2Fwww.stemcellsciencenews.com%5C%2Fwp-content%5C%2Fplugins%5C%2Fzotpress%5C%2Flib%5C%2Frequest%5C%2Frequest.cite.php%3Fapi_user_id%3D6445218%26amp%3Bitem_key%3DZEFT6DBL%27%3ECite%3C%5C%2Fa%3E%20%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Sox9%20and%20Rbpj%20differentially%20regulate%20endothelial%20to%20mesenchymal%20transition%20and%20wound%20scarring%20in%20murine%20endovascular%20progenitors%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jilai%22%2C%22lastName%22%3A%22Zhao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jatin%22%2C%22lastName%22%3A%22Patel%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Simranpreet%22%2C%22lastName%22%3A%22Kaur%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Seen-Ling%22%2C%22lastName%22%3A%22Sim%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ho%20Yi%22%2C%22lastName%22%3A%22Wong%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Cassandra%22%2C%22lastName%22%3A%22Styke%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Isabella%22%2C%22lastName%22%3A%22Hogan%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sam%22%2C%22lastName%22%3A%22Kahler%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Hamish%22%2C%22lastName%22%3A%22Hamilton%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Racheal%22%2C%22lastName%22%3A%22Wadlow%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22James%22%2C%22lastName%22%3A%22Dight%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ghazaleh%22%2C%22lastName%22%3A%22Hashemi%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Laura%22%2C%22lastName%22%3A%22Sormani%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Edwige%22%2C%22lastName%22%3A%22Roy%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mervin%20C.%22%2C%22lastName%22%3A%22Yoder%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mathias%22%2C%22lastName%22%3A%22Francois%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Kiarash%22%2C%22lastName%22%3A%22Khosrotehrani%22%7D%5D%2C%22abstractNote%22%3A%22Endothelial%20to%20mesenchymal%20transition%20%28EndMT%29%20is%20a%20leading%20cause%20of%20fibrosis%20and%20disease%2C%20however%20its%20mechanism%20has%20yet%20to%20be%20elucidated.%20The%20endothelium%20possesses%20a%20profound%20regenerative%20capacity%20to%20adapt%20and%20reorganize%20that%20is%20attributed%20to%20a%20population%20of%20vessel-resident%20endovascular%20progenitors%20%28EVP%29%20governing%20an%20endothelial%20hierarchy.%20Here%2C%20using%20fate%20analysis%2C%20we%20show%20that%20two%20transcription%20factors%20SOX9%20and%20RBPJ%20specifically%20affect%20the%20murine%20EVP%20numbers%20and%20regulate%20lineage%20specification.%20Conditional%20knock-out%20of%20Sox9%20from%20the%20vasculature%20%28Sox9fl%5C%2Ffl%5C%2FCdh5-CreER%20RosaYFP%29%20depletes%20EVP%20while%20enhancing%20Rbpj%20expression%20and%20canonical%20Notch%20signalling.%20Additionally%2C%20skin%20wound%20analysis%20from%20Sox9%20conditional%20knock-out%20mice%20demonstrates%20a%20significant%20reduction%20in%20pathological%20EndMT%20resulting%20in%20reduced%20scar%20area.%20The%20converse%20is%20observed%20with%20Rbpj%20conditionally%20knocked-out%20from%20the%20murine%20vasculature%20%28Rbpjfl%5C%2Ffl%5C%2FCdh5-CreER%20RosaYFP%29%20or%20inhibition%20of%20Notch%20signaling%20in%20human%20endothelial%20colony%20forming%20cells%2C%20resulting%20in%20enhanced%20Sox9%20and%20EndMT%20related%20gene%20%28Snail%2C%20Slug%2C%20Twist1%2C%20Twist2%2C%20TGF-%5Cu03b2%29%20expression.%20Similarly%2C%20increased%20endothelial%20hedgehog%20signaling%20%28Ptch1fl%5C%2Ffl%5C%2FCdh5-CreER%20RosaYFP%29%2C%20that%20upregulates%20the%20expression%20of%20Sox9%20in%20cells%20undergoing%20pathological%20EndMT%2C%20also%20results%20in%20excess%20fibrosis.%20Endothelial%20cells%20transitioning%20to%20a%20mesenchymal%20fate%20express%20increased%20Sox9%2C%20reduced%20Rbpj%20and%20enhanced%20EndMT.%20Importantly%2C%20using%20topical%20administration%20of%20siRNA%20against%20Sox9%20on%20skin%20wounds%20can%20substantially%20reduce%20scar%20area%20by%20blocking%20pathological%20EndMT.%20Overall%2C%20here%20we%20report%20distinct%20fates%20of%20EVPs%20according%20to%20the%20relative%20expression%20of%20Rbpj%20or%20Notch%20signalling%20and%20Sox9%2C%20highlighting%20their%20potential%20plasticity%20and%20opening%20exciting%20avenues%20for%20more%20effective%20therapies%20in%20fibrotic%20diseases.%22%2C%22date%22%3A%222021-05-07%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1038%5C%2Fs41467-021-22717-9%22%2C%22ISSN%22%3A%222041-1723%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.nature.com%5C%2Farticles%5C%2Fs41467-021-22717-9%22%2C%22collections%22%3A%5B%5D%2C%22dateModified%22%3A%222021-05-07T22%3A58%3A04Z%22%7D%7D%5D%7D
Zhao, J., Patel, J., Kaur, S., Sim, S.-L., Wong, H. Y., Styke, C., Hogan, I., Kahler, S., Hamilton, H., Wadlow, R., Dight, J., Hashemi, G., Sormani, L., Roy, E., Yoder, M. C., Francois, M., & Khosrotehrani, K. (2021). Sox9 and Rbpj differentially regulate endothelial to mesenchymal transition and wound scarring in murine endovascular progenitors. Nature Communications, 12(1), 2564. https://doi.org/10.1038/s41467-021-22717-9 Cite
