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Series GSE181610 Query DataSets for GSE181610
Status Public on Aug 07, 2021
Title PCSK9 is involved in human induced pluripotent stem cell proliferation through the regulation of the NODAL signaling pathway II
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Proprotein convertase subtilisin kexin type 9 (PCSK9) is a key regulator of LDL cholesterol metabolism and the target of lipid-lowering drugs. PCSK9 is mainly expressed in hepatocyte. Here, we show that PCSK9 is highly expressed in undifferentiated hiPSCs. PCSK9 inhibition in hiPSCs with the use of shRNA, CRISPR/cas9-mediated knockout or endogenous PCSK9 loss-of-function mutation R104C/V114A unveiled its new role as a potential cell cycle regulator through the NODAL signaling pathway. Indeed, PCSK9 inhibition leads to a decrease of SMAD2 phosphorylation and hiPSCs proliferation. Conversely, PCSK9 overexpression stimulates hiPSCs proliferation. PCSK9 can interfere with the NODAL pathway by regulating the expression of its endogenous inhibitor DACT2, which is involved in the TGFß-R1 lysosomal degradation. Using different PCSK9 constructs we show that PCSK9 interacts with DACT2 through its CHRD domain. Altogether these data highlight a new role of PCSK9 in cellular proliferation and development, beyond its canonical effect on lipid metabolism.
Overall design PCSK9 gene expression has been silenced upon lentiviral transduction of specific shRNA (Sigma). The clone TRCN0000075236 cloned into the pLKO.1-Puro vector has been used to target PCSK9 (N=3) while an unspecific shRNA sequence has been used as control (N=3). Upon transduction, K3 hiPSC (Si-Tayeb et al., 2010) were subjected to Puromycin (TOCRIS Bioscience 4089/50) selection using a concentration up to 8µg/ml.
Contributor(s) Si-Tayeb K, Rimbert A
Citation(s) 34739847
Submission date Aug 06, 2021
Last update date Nov 09, 2021
Contact name Antoine Rimbert
Organization name Institut du thorax inserm-U1087
Street address 8 quai moncousu
City Nantes
ZIP/Postal code 44300
Country France
Platforms (1)
GPL13607 Agilent-028004 SurePrint G3 Human GE 8x60K Microarray (Feature Number version)
Samples (6)
GSM5508132 FhiPS_shCt_1_N4B
GSM5508133 FhiPS_shCt_2_N5B
GSM5508134 FhiPS_shCt_3_N6B
BioProject PRJNA752648

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Supplementary file Size Download File type/resource
GSE181610_RAW.tar 133.2 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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