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| 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
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| 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.
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| 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.
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| 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 |
| E-mail(s) |
antoine.rimbert3@gmail.com
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| Organization name |
Institut du thorax inserm-U1087
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| Street address |
8 quai moncousu
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| City |
Nantes |
| ZIP/Postal code |
44300 |
| Country |
France |
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| Platforms (1) |
| GPL13607 |
Agilent-028004 SurePrint G3 Human GE 8x60K Microarray (Feature Number version) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA752648 |
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