CENTRE HOSPITALIER UNIVERSITAIRE DE NANTES;CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS);UNIVERSITÉ DE NANTES;NSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE);HCS PHARMA
发明人:
Karim SI TAYEB,Salam IDRISS,Bertrand CARIOU,Méryl ROUDAUT,Cédric LE MAY,Amandine CAILLAUD
申请号：
US16349337
公开号：
US20190345500A1
申请日:
2017.11.14
申请国别(地区):
US
年份:
2019
代理人:
摘要：
The present invention relates to a method for modulating stem cells proliferation or differentiation comprising a step of contacting said stem cells with an effective amount of an activator or inhibitor of a proprotein convertase subtilisin kexin 9 (PCSK9). Inventors performed a global transcriptomic analyses in hiPSCs and showed that PCSK9 inhibition by shRNA and the intracellular PCSK9-R104C/V114A mutation negatively regulate the NODAL signaling pathway and its targets. This regulation was manifested in drastic reduction P-SMAD2/total SMAD2 protein level. This was accompanied by reduced proliferation rate where hiPSC-shPCSK9 and hiPSC-R104C/V114A demanded >；1.3-fold more time to double compared to their control counterparts. They showed that PCSK9 was regulating this signaling pathway through direct physical interaction with DACT2, an intracellular attenuator of NODAL receptor and favoring its protein degradation. Thus, these findings allow to understand the differentiation and proliferation of cells.
