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  1. Article ; Online: Generation of a GPR146 knockout human induced pluripotent stem cell line (ITXi001-A-1).

    Bray, Lise / Caillaud, Amandine / Girardeau, Aurore / Patitucci, Murielle / Le May, Cédric / Cariou, Bertrand / Rimbert, Antoine

    Stem cell research

    2022  Volume 60, Page(s) 102721

    Abstract: Dyslipidemia is a key modifiable causal risk factor involved in the development of atherosclerotic cardiovascular disease. Recently, the G protein-coupled receptor 146 (GPR146), a member of the G-coupled protein receptors' family, has been shown to be a ... ...

    Abstract Dyslipidemia is a key modifiable causal risk factor involved in the development of atherosclerotic cardiovascular disease. Recently, the G protein-coupled receptor 146 (GPR146), a member of the G-coupled protein receptors' family, has been shown to be a regulator of plasma cholesterol. Inhibition of hepatic GPR146 in mice displays protective effect against both hypercholesterolemia and atherosclerosis. Here, we characterize a genetically engineered human induced pluripotent stem cell (hiPSC) model invalidated for GPR146 (ITXi001-A-1) using CRISPR-Cas9 editing technology. Differentiation of ITXi001-A-1 towards hepatic fate will provide a suitable model for deciphering the molecular mechanisms sustaining the beneficial metabolic effects of GPR146 inhibition.
    MeSH term(s) Animals ; CRISPR-Cas Systems/genetics ; Cell Differentiation ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Liver ; Mice
    Language English
    Publishing date 2022-02-25
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2393143-7
    ISSN 1876-7753 ; 1873-5061
    ISSN (online) 1876-7753
    ISSN 1873-5061
    DOI 10.1016/j.scr.2022.102721
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Generation of an induced pluripotent stem cell line (ITXi012-A) from a patient with genetically determined high-lipoprotein(a) plasma levels.

    Caillaud, Amandine / Bray, Lise / Girardeau, Aurore / Begué-Racapé, Zoé / Vince, Lucie / Patitucci, Murielle / Le May, Cédric / Lambert, Gilles / Cariou, Bertrand / Rimbert, Antoine

    Stem cell research

    2023  Volume 72, Page(s) 103205

    Abstract: Elevated circulating lipoprotein(a) (Lp(a)) is a genetically determined risk factor for coronary artery disease and aortic valve stenosis (Tsimikas, 2017). Importantly, the LPA gene, which encodes the apolipoprotein(a) (protein-component of Lp(a)), is ... ...

    Abstract Elevated circulating lipoprotein(a) (Lp(a)) is a genetically determined risk factor for coronary artery disease and aortic valve stenosis (Tsimikas, 2017). Importantly, the LPA gene, which encodes the apolipoprotein(a) (protein-component of Lp(a)), is missing in most species, and human liver cell-lines do not secrete Lp(a). There is a need for the development of human in vitro models suitable for investigating biological mechanisms involved in Lp(a) metabolism. We here generated and characterized iPSCs from a patient with extremely high Lp(a) plasma levels genetically determined (Coassin et al., 2022). This unique cellular model offers great opportunities and new perspectives for investigations on biological mechanisms involved in Lp(a) metabolism.
    MeSH term(s) Humans ; Lipoprotein(a)/genetics ; Lipoprotein(a)/metabolism ; Aortic Valve/metabolism ; Induced Pluripotent Stem Cells/metabolism ; Aortic Valve Stenosis/etiology ; Aortic Valve Stenosis/genetics ; Coronary Artery Disease/etiology ; Coronary Artery Disease/genetics ; Risk Factors
    Chemical Substances Lipoprotein(a)
    Language English
    Publishing date 2023-09-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 2393143-7
    ISSN 1876-7753 ; 1873-5061
    ISSN (online) 1876-7753
    ISSN 1873-5061
    DOI 10.1016/j.scr.2023.103205
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Generation of a GPR146 knockout human induced pluripotent stem cell line (ITXi001-A-1)

    Lise Bray / Amandine Caillaud / Aurore Girardeau / Murielle Patitucci / Cédric Le May / Bertrand Cariou / Antoine Rimbert

    Stem Cell Research, Vol 60, Iss , Pp 102721- (2022)

    2022  

    Abstract: Dyslipidemia is a key modifiable causal risk factor involved in the development of atherosclerotic cardiovascular disease. Recently, the G protein-coupled receptor 146 (GPR146), a member of the G-coupled protein receptors’ family, has been shown to be a ... ...

    Abstract Dyslipidemia is a key modifiable causal risk factor involved in the development of atherosclerotic cardiovascular disease. Recently, the G protein-coupled receptor 146 (GPR146), a member of the G-coupled protein receptors’ family, has been shown to be a regulator of plasma cholesterol. Inhibition of hepatic GPR146 in mice displays protective effect against both hypercholesterolemia and atherosclerosis. Here, we characterize a genetically engineered human induced pluripotent stem cell (hiPSC) model invalidated for GPR146 (ITXi001-A-1) using CRISPR-Cas9 editing technology. Differentiation of ITXi001-A-1 towards hepatic fate will provide a suitable model for deciphering the molecular mechanisms sustaining the beneficial metabolic effects of GPR146 inhibition.
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2022-04-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Generation of an induced pluripotent stem cell line (ITXi012-A) from a patient with genetically determined high-lipoprotein(a) plasma levels

    Amandine Caillaud / Lise Bray / Aurore Girardeau / Zoé Begué-Racapé / Lucie Vince / Murielle Patitucci / Cédric Le May / Gilles Lambert / Bertrand Cariou / Antoine Rimbert

    Stem Cell Research, Vol 72, Iss , Pp 103205- (2023)

    2023  

    Abstract: Elevated circulating lipoprotein(a) (Lp(a)) is a genetically determined risk factor for coronary artery disease and aortic valve stenosis (Tsimikas, 2017). Importantly, the LPA gene, which encodes the apolipoprotein(a) (protein-component of Lp(a)), is ... ...

    Abstract Elevated circulating lipoprotein(a) (Lp(a)) is a genetically determined risk factor for coronary artery disease and aortic valve stenosis (Tsimikas, 2017). Importantly, the LPA gene, which encodes the apolipoprotein(a) (protein-component of Lp(a)), is missing in most species, and human liver cell-lines do not secrete Lp(a). There is a need for the development of human in vitro models suitable for investigating biological mechanisms involved in Lp(a) metabolism. We here generated and characterized iPSCs from a patient with extremely high Lp(a) plasma levels genetically determined (Coassin et al., 2022). This unique cellular model offers great opportunities and new perspectives for investigations on biological mechanisms involved in Lp(a) metabolism.
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2023-10-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Les organoïdes hépatiques - Quels sont les enjeux ?

    Luce, Eléanor / Messina, Antonietta / Caillaud, Amandine / Si-Tayeb, Karim / Cariou, Bertrand / Bur, Etienne / Dubart-Kupperschmitt, Anne / Duclos-Vallée, Jean-Charles

    Medecine sciences : M/S

    2021  Volume 37, Issue 10, Page(s) 902–909

    Abstract: The study and understanding of liver organogenesis have allowed the development of protocols for pluripotent stem cells differentiation to overcome the lack of primary cells, providing an almost unlimited source of liver cells. However, as their ... ...

    Title translation Hepatic organoids: What are the challenges?
    Abstract The study and understanding of liver organogenesis have allowed the development of protocols for pluripotent stem cells differentiation to overcome the lack of primary cells, providing an almost unlimited source of liver cells. However, as their differentiation in conventional 2D culture systems has shown serious limits, hepatic organoids derived from human pluripotent stem cells represent a promising alternative. These complex and organized structures, containing one or more cell types, make it possible to recapitulate in vitro some of the organ functions, thus enabling numerous applications such as the study of the liver development, the mass production of functional liver cells for transplantation or the development of bioartificial livers, as well as the in vitro modeling of hepatic pathologies allowing high throughput applications in drug screening or toxicity studies. Economic and ethical issues must also be taken into account before using these organoids in therapeutic applications.
    MeSH term(s) Cell Differentiation ; Hepatocytes ; Humans ; Induced Pluripotent Stem Cells ; Liver ; Organoids ; Pluripotent Stem Cells
    Language French
    Publishing date 2021-10-14
    Publishing country France
    Document type Journal Article
    ZDB-ID 632733-3
    ISSN 1958-5381 ; 0767-0974
    ISSN (online) 1958-5381
    ISSN 0767-0974
    DOI 10.1051/medsci/2021119
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.B 2872: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  6. Article ; Online: APOB

    Vanhoye, Xavier / Janin, Alexandre / Caillaud, Amandine / Rimbert, Antoine / Venet, Fabienne / Gossez, Morgane / Dijk, Wieneke / Marmontel, Oriane / Nony, Séverine / Chatelain, Charlotte / Durand, Christine / Lindenbaum, Pierre / Rieusset, Jennifer / Cariou, Bertrand / Moulin, Philippe / Di Filippo, Mathilde

    International journal of molecular sciences

    2022  Volume 23, Issue 8

    Abstract: Hypobetalipoproteinemia is characterized by LDL-cholesterol and apolipoprotein B (apoB) plasma levels below the fifth percentile for age and sex. Familial hypobetalipoproteinemia (FHBL) is mostly caused by premature termination codons in ... ...

    Abstract Hypobetalipoproteinemia is characterized by LDL-cholesterol and apolipoprotein B (apoB) plasma levels below the fifth percentile for age and sex. Familial hypobetalipoproteinemia (FHBL) is mostly caused by premature termination codons in the
    MeSH term(s) Apolipoproteins B/metabolism ; CRISPR-Cas Systems ; Fatty Liver/genetics ; Humans ; Hypobetalipoproteinemia, Familial, Apolipoprotein B/genetics ; Hypobetalipoproteinemias/diagnosis ; Hypobetalipoproteinemias/genetics ; Hypobetalipoproteinemias/metabolism
    Chemical Substances Apolipoproteins B
    Language English
    Publishing date 2022-04-13
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23084281
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  7. Article ; Online: Generation of three human induced pluripotent stem cell lines with IRX5 knockout and knockin genetic editions using CRISPR-Cas9 system

    Robin Canac / Amandine Caillaud / Bastien Cimarosti / Aurore Girardeau / Hanan Hamamy / Bruno Reversade / Carine Bonnard / Zeina R. Al Sayed / Laurent David / Jeremie Poschmann / Patricia Lemarchand / Guillaume Lamirault / Nathalie Gaborit

    Stem Cell Research, Vol 58, Iss , Pp 102627- (2022)

    2022  

    Abstract: Studies on animal models have shown that Irx5 is an important regulator of cardiac development and that it regulates ventricular electrical repolarization gradient in the adult heart. Mutations in IRX5 have also been linked in humans to cardiac ... ...

    Abstract Studies on animal models have shown that Irx5 is an important regulator of cardiac development and that it regulates ventricular electrical repolarization gradient in the adult heart. Mutations in IRX5 have also been linked in humans to cardiac conduction defects. In order to fully characterize the role of IRX5 during cardiac development and in cardiomyocyte function, we generated three genetically-modified human induced pluripotent stem cell lines: two knockout lines (heterozygous and homozygous) and a knockin HA-tagged line (homozygous).
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: FACS-assisted CRISPR-Cas9 genome editing of human induced pluripotent stem cells.

    Caillaud, Amandine / Lévêque, Antoine / Thédrez, Aurélie / Girardeau, Aurore / Canac, Robin / Bray, Lise / Baudic, Manon / Barc, Julien / Gaborit, Nathalie / Lamirault, Guillaume / Gardie, Betty / Idriss, Salam / Rimbert, Antoine / Le May, Cédric / Cariou, Bertrand / Si-Tayeb, Karim

    STAR protocols

    2022  Volume 3, Issue 4, Page(s) 101680

    Abstract: This manuscript proposes an efficient and reproducible protocol for the generation of genetically modified human induced pluripotent stem cells (hiPSCs) by genome editing using CRISPR-Cas9 technology. Here, we describe the experimental strategy for ... ...

    Abstract This manuscript proposes an efficient and reproducible protocol for the generation of genetically modified human induced pluripotent stem cells (hiPSCs) by genome editing using CRISPR-Cas9 technology. Here, we describe the experimental strategy for generating knockout (KO) and knockin (KI) clonal populations of hiPSCs using single-cell sorting by flow cytometry. We efficiently achieved up to 15 kb deletions, molecular tag insertions, and single-nucleotide editing in hiPSCs. We emphasize the efficacy of this approach in terms of cell culture time. For complete details on the use and execution of this protocol, please refer to Canac et al. (2022) and Bray et al. (2022).
    MeSH term(s) Humans ; Gene Editing/methods ; CRISPR-Cas Systems ; Induced Pluripotent Stem Cells ; Clone Cells ; Cell Culture Techniques
    Language English
    Publishing date 2022-09-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2666-1667
    ISSN (online) 2666-1667
    DOI 10.1016/j.xpro.2022.101680
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: PCSK9 regulates the NODAL signaling pathway and cellular proliferation in hiPSCs.

    Roudaut, Meryl / Idriss, Salam / Caillaud, Amandine / Girardeau, Aurore / Rimbert, Antoine / Champon, Benoite / David, Amandine / Lévêque, Antoine / Arnaud, Lucie / Pichelin, Matthieu / Prieur, Xavier / Prat, Annik / Seidah, Nabil G / Zibara, Kazem / Le May, Cedric / Cariou, Bertrand / Si-Tayeb, Karim

    Stem cell reports

    2021  Volume 16, Issue 12, Page(s) 2958–2972

    Abstract: Proprotein convertase subtilisin kexin type 9 (PCSK9) is a key regulator of low-density lipoprotein (LDL) cholesterol metabolism and the target of lipid-lowering drugs. PCSK9 is mainly expressed in hepatocytes. Here, we show that PCSK9 is highly ... ...

    Abstract Proprotein convertase subtilisin kexin type 9 (PCSK9) is a key regulator of low-density lipoprotein (LDL) cholesterol metabolism and the target of lipid-lowering drugs. PCSK9 is mainly expressed in hepatocytes. Here, we show that PCSK9 is highly expressed in undifferentiated human induced pluripotent stem cells (hiPSCs). PCSK9 inhibition in hiPSCs with the use of short hairpin RNA (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. In fact, 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 transforming growth factor (TGF) β-R1 lysosomal degradation. Using different PCSK9 constructs, we show that PCSK9 interacts with DACT2 through its Cys-His-rich domain (CHRD) domain. Altogether these data highlight a new role of PCSK9 in cellular proliferation and development.
    MeSH term(s) Adaptor Proteins, Signal Transducing/metabolism ; Cell Differentiation ; Cell Line ; Cell Membrane/metabolism ; Cell Proliferation ; Gene Expression Regulation ; Humans ; Induced Pluripotent Stem Cells/cytology ; Induced Pluripotent Stem Cells/metabolism ; Loss of Function Mutation ; Nodal Protein/genetics ; Nodal Protein/metabolism ; Phosphorylation ; Proprotein Convertase 9/chemistry ; Proprotein Convertase 9/deficiency ; Proprotein Convertase 9/genetics ; Proprotein Convertase 9/metabolism ; Protein Binding ; Protein Domains ; Receptors, Transforming Growth Factor beta/metabolism ; Signal Transduction ; Smad2 Protein/metabolism ; Up-Regulation
    Chemical Substances Adaptor Proteins, Signal Transducing ; DACT2 protein, human ; Nodal Protein ; Receptors, Transforming Growth Factor beta ; Smad2 Protein ; Proprotein Convertase 9 (EC 3.4.21.-)
    Language English
    Publishing date 2021-11-04
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2720528-9
    ISSN 2213-6711 ; 2213-6711
    ISSN (online) 2213-6711
    ISSN 2213-6711
    DOI 10.1016/j.stemcr.2021.10.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Generation of three human induced pluripotent stem cell lines with IRX5 knockout and knockin genetic editions using CRISPR-Cas9 system.

    Canac, Robin / Caillaud, Amandine / Cimarosti, Bastien / Girardeau, Aurore / Hamamy, Hanan / Reversade, Bruno / Bonnard, Carine / Al Sayed, Zeina R / David, Laurent / Poschmann, Jeremie / Lemarchand, Patricia / Lamirault, Guillaume / Gaborit, Nathalie

    Stem cell research

    2021  Volume 58, Page(s) 102627

    Abstract: Studies on animal models have shown that Irx5 is an important regulator of cardiac development and that it regulates ventricular electrical repolarization gradient in the adult heart. Mutations in IRX5 have also been linked in humans to cardiac ... ...

    Abstract Studies on animal models have shown that Irx5 is an important regulator of cardiac development and that it regulates ventricular electrical repolarization gradient in the adult heart. Mutations in IRX5 have also been linked in humans to cardiac conduction defects. In order to fully characterize the role of IRX5 during cardiac development and in cardiomyocyte function, we generated three genetically-modified human induced pluripotent stem cell lines: two knockout lines (heterozygous and homozygous) and a knockin HA-tagged line (homozygous).
    MeSH term(s) Animals ; CRISPR-Cas Systems/genetics ; Heterozygote ; Homeodomain Proteins/genetics ; Homeodomain Proteins/metabolism ; Homozygote ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Myocytes, Cardiac/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism
    Chemical Substances Homeodomain Proteins ; IRX5 protein, human ; Transcription Factors
    Language English
    Publishing date 2021-12-13
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2393143-7
    ISSN 1876-7753 ; 1873-5061
    ISSN (online) 1876-7753
    ISSN 1873-5061
    DOI 10.1016/j.scr.2021.102627
    Database MEDical Literature Analysis and Retrieval System OnLINE

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