Generation of Marfan syndrome-specific induced pluripotent stem cells harboring FBN1 mutations
Francesca Vacante1, Ravichandra Venkateshappa1, Min Htet2
1Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Abstract:
Marfan syndrome (MFS) is a hereditary condition caused by mutations in the FBN1 gene. Genetic mutations in the FBN1 locus impact the function of the encoded protein, Fibrillin 1, a structural molecule forming microfibrils found in the connective tissue. MFS patients develop severe cardiovascular complications including thoracic aortic aneurysm and aortic dissection, which predispose them to an enhanced risk of premature death. Here, we generated two induced pluripotent stem cell (iPSC) lines harboring mutations in the FBN1 gene (p.C1942C>A and c.1954 T>C), directly derived from MFS patients. We have shown that both iPSC lines displayed expression of pluripotency markers, normal karyotype and ability of trilineage differentiation, representing a valuable tool for the identification of new therapeutic strategies for intervening in this disease.
Insights
Researchers created Marfan syndrome (MFS) patient-derived induced pluripotent stem cells (iPSCs) with FBN1 gene mutations. These MFS iPSC lines are valuable for developing new therapeutic strategies for this connective tissue disorder.
Area of Science:
- Genetics
- Stem Cell Biology
- Cardiovascular Research
Background:
- Marfan syndrome (MFS) is an inherited connective tissue disorder caused by FBN1 gene mutations.
- FBN1 mutations affect Fibrillin 1, crucial for connective tissue integrity.
- MFS leads to life-threatening cardiovascular issues like aortic aneurysms and dissections.
Purpose of the Study:
- To generate and characterize induced pluripotent stem cell (iPSC) lines from Marfan syndrome patients.
- To establish a cellular model for studying FBN1-related connective tissue disorders.
- To provide a tool for identifying novel therapeutic interventions for Marfan syndrome.
Main Methods:
- Isolation of patient-derived cells and reprogramming into induced pluripotent stem cells (iPSCs).
- Generation of two distinct iPSC lines with specific FBN1 mutations (p.C1942C>A and c.1954 T>C).
- Assessment of pluripotency markers, karyotype stability, and trilineage differentiation potential.
Main Results:
- Successfully generated two Marfan syndrome patient-derived iPSC lines.
- Confirmed expression of pluripotency markers in both iPSC lines.
- Demonstrated normal karyotype and successful trilineage differentiation capacity.
Conclusions:
- The developed Marfan syndrome iPSC lines are genetically relevant and functionally validated.
- These iPSC lines serve as a robust in vitro model for Marfan syndrome research.
- The established cell lines offer a valuable platform for discovering and testing new therapeutic strategies for MFS.
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