دورية أكاديمية
أعرض في EDS

Quantitative proteomics reveal lineage-specific protein profiles in iPSC-derived Marfan syndrome smooth muscle cells.

التفاصيل البيبلوغرافية
العنوان: Quantitative proteomics reveal lineage-specific protein profiles in iPSC-derived Marfan syndrome smooth muscle cells.
المؤلفون: Iosef C; Department of Cardiothoracic Surgery, Stanford University, 300 Pasteur Dr, Falk CVRB, Stanford, CA, 94305, USA., Pedroza AJ; Department of Cardiothoracic Surgery, Stanford University, 300 Pasteur Dr, Falk CVRB, Stanford, CA, 94305, USA., Cui JZ; Department of Cardiothoracic Surgery, Stanford University, 300 Pasteur Dr, Falk CVRB, Stanford, CA, 94305, USA., Dalal AR; Department of Cardiothoracic Surgery, Stanford University, 300 Pasteur Dr, Falk CVRB, Stanford, CA, 94305, USA., Arakawa M; Department of Cardiothoracic Surgery, Stanford University, 300 Pasteur Dr, Falk CVRB, Stanford, CA, 94305, USA., Tashima Y; Department of Cardiothoracic Surgery, Stanford University, 300 Pasteur Dr, Falk CVRB, Stanford, CA, 94305, USA., Koyano TK; Department of Cardiothoracic Surgery, Stanford University, 300 Pasteur Dr, Falk CVRB, Stanford, CA, 94305, USA., Burdon G; Department of Cardiothoracic Surgery, Stanford University, 300 Pasteur Dr, Falk CVRB, Stanford, CA, 94305, USA., Churovich SMP; Department of Cardiothoracic Surgery, Stanford University, 300 Pasteur Dr, Falk CVRB, Stanford, CA, 94305, USA., Orrick JO; Department of Cardiothoracic Surgery, Stanford University, 300 Pasteur Dr, Falk CVRB, Stanford, CA, 94305, USA., Pariani M; Department of Pediatrics-Genetics, Stanford University, Stanford, CA, USA., Fischbein MP; Department of Cardiothoracic Surgery, Stanford University, 300 Pasteur Dr, Falk CVRB, Stanford, CA, 94305, USA. mfischbe@stanford.edu.
المصدر: Scientific reports [Sci Rep] 2020 Nov 23; Vol. 10 (1), pp. 20392. Date of Electronic Publication: 2020 Nov 23.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH: Aorta/*metabolism , Aortic Aneurysm, Thoracic/*genetics , Induced Pluripotent Stem Cells/*metabolism , Marfan Syndrome/*genetics , Neural Crest/*metabolism , Proteomics/*methods, Aorta/pathology ; Aortic Aneurysm, Thoracic/metabolism ; Aortic Aneurysm, Thoracic/pathology ; Case-Control Studies ; Cell Adhesion ; Cell Differentiation ; Cell Lineage/genetics ; Female ; Fibrillin-1/genetics ; Fibrillin-1/metabolism ; Fibronectins/genetics ; Fibronectins/metabolism ; Gene Expression Profiling ; Gene Expression Regulation ; Humans ; Induced Pluripotent Stem Cells/pathology ; Integrins/genetics ; Integrins/metabolism ; Laminin/genetics ; Laminin/metabolism ; Leukocytes, Mononuclear/metabolism ; Leukocytes, Mononuclear/pathology ; Mannose-Binding Lectins/genetics ; Mannose-Binding Lectins/metabolism ; Marfan Syndrome/metabolism ; Marfan Syndrome/pathology ; Membrane Glycoproteins/genetics ; Membrane Glycoproteins/metabolism ; Mesoderm/metabolism ; Mesoderm/pathology ; Neural Crest/pathology ; Primary Cell Culture ; Receptors, Cell Surface/genetics ; Receptors, Cell Surface/metabolism ; Young Adult
مستخلص: Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the FBN1 gene that produces wide disease phenotypic variability. The lack of ample genotype-phenotype correlation hinders translational study development aimed at improving disease prognosis. In response to this need, an induced pluripotent stem cell (iPSC) disease model has been used to test patient-specific cells by a proteomic approach. This model has the potential to risk stratify patients to make clinical decisions, including timing for surgical treatment. The regional propensity for aneurysm formation in MFS may be related to distinct smooth muscle cell (SMC) embryologic lineages. Thus, peripheral blood mononuclear cell (PBMC)-derived induced pluripotent stem cells (iPSC) were differentiated into lateral mesoderm (LM, aortic root) and neural crest (NC, ascending aorta/transverse arch) SMC lineages to model MFS aortic pathology. Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) proteomic analysis by tandem mass spectrometry was applied to profile LM and NC iPSC SMCs from four MFS patients and two healthy controls. Analysis revealed 45 proteins with lineage-dependent expression in MFS patients, many of which were specific to diseased samples. Single protein-level data from both iPSC SMCs and primary MFS aortic root aneurysm tissue confirmed elevated integrin αV and reduced MRC2 in clinical disease specimens, validating the iPSC iTRAQ findings. Functionally, iPSC SMCs exhibited defective adhesion to a variety of extracellular matrix proteins, especially laminin-1 and fibronectin, suggesting altered cytoskeleton dynamics. This study defines the aortic embryologic origin-specific proteome in a validated iPSC SMC model to identify novel protein markers associated with MFS aneurysm phenotype. Translating iPSC findings into clinical aortic aneurysm tissue samples highlights the potential for iPSC-based methods to model MFS disease for mechanistic studies and therapeutic discovery in vitro.
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معلومات مُعتمدة: R25 HL147666 United States HL NHLBI NIH HHS; R38 HL143615 United States HL NHLBI NIH HHS; R01 AR066629 United States AR NIAMS NIH HHS
المشرفين على المادة: 0 (FBN1 protein, human)
0 (Fibrillin-1)
0 (Fibronectins)
0 (ITGA5 protein, human)
0 (Integrins)
0 (Laminin)
0 (MRC2 protein, human)
0 (Mannose-Binding Lectins)
0 (Membrane Glycoproteins)
0 (Receptors, Cell Surface)
0 (laminin 1)
تواريخ الأحداث: Date Created: 20201124 Date Completed: 20210416 Latest Revision: 20240310
رمز التحديث: 20240310
مُعرف محوري في PubMed: PMC7683538
DOI: 10.1038/s41598-020-77274-w
PMID: 33230159
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-2322
DOI:10.1038/s41598-020-77274-w