The development and application of iPS technology promises to revolutionize the understanding and treatment of disease. In particular, it has previously been extremely difficult to obtain sufficient amounts of the relevant human cell types, including cardiac myocytes, endothelial cells and vascular smooth muscle cells, to explore the mechanisms underlying cardiovascular diseases. As such, the ability to reprogram patient specific iPS cells to create cell based disease models represents a major and important paradigm shift for our community. We successfully generated in excess of 30 human iPS cell lines, including approximately 10 patient specific cell lines. To date, these patient specific cell lines have included individuals with Jobs syndrome, as well as an additional rare syndrome characterized by a circulating monocyte deficiency. We have been successful using both lentiviral and retroviral delivery of the four requisite pluripotent factors. We have also extensively characterized many of the human iPS cell lines generated. Our iPS cell lines exhibit characteristics of human embryonic stem cells (ESC) including the ability to form embroid bodies. In addition, these cells express high levels of alkaline phosphatase , Oct4, and Nanog, as well as the human ESC markers SSEA4 and Tra-1-60. Furthermore, we have confirmed that these cells manifest a normal karyotyp and have already begun to develop protocols for differentiation of these iPS cells down various ectodermal, mesodermal and endodermal lineages as assessed by the respective expression of Nestin, Runx1 and GATA4. Successful differentiation of iPS cells towards lineages that are relevant for cardiovascular disease, including endothelial cells, has already been achieved.

Project Start
Project End
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Budget End
Support Year
1
Fiscal Year
2010
Total Cost
$396,348
Indirect Cost
Name
National Heart, Lung, and Blood Institute
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Type
DUNS #
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Vallabhaneni, Haritha; Lynch, Patrick J; Chen, Guibin et al. (2018) High Basal Levels of ?H2AX in Human Induced Pluripotent Stem Cells Are Linked to Replication-Associated DNA Damage and Repair. Stem Cells :
Zhou, Qing; Yu, Xiaomin; Demirkaya, Erkan et al. (2016) Biallelic hypomorphic mutations in a linear deubiquitinase define otulipenia, an early-onset autoinflammatory disease. Proc Natl Acad Sci U S A 113:10127-32
Jin, Hui; St Hilaire, Cynthia; Huang, Yuting et al. (2016) Increased activity of TNAP compensates for reduced adenosine production and promotes ectopic calcification in the genetic disease ACDC. Sci Signal 9:ra121
Hox, Valerie; O'Connell, Michael P; Lyons, Jonathan J et al. (2016) Diminution of signal transducer and activator of transcription 3 signaling inhibits vascular permeability and anaphylaxis. J Allergy Clin Immunol 138:187-99
Janecke, Andreas R; Li, Ben; Boehm, Manfred et al. (2016) The phenotype of the musculocontractural type of Ehlers-Danlos syndrome due to CHST14 mutations. Am J Med Genet A 170A:103-15
Lubick, Kirk J; Robertson, Shelly J; McNally, Kristin L et al. (2015) Flavivirus Antagonism of Type I Interferon Signaling Reveals Prolidase as a Regulator of IFNAR1 Surface Expression. Cell Host Microbe 18:61-74
Zhou, Qing; Yang, Dan; Ombrello, Amanda K et al. (2014) Early-onset stroke and vasculopathy associated with mutations in ADA2. N Engl J Med 370:911-20
Negro, Alejandra; Boehm, Manfred (2014) Cardiomyocyte maturation: It takes a village to raise a kid. J Mol Cell Cardiol 74:193-5
Sangaré, Modibo; Hendrickson, Brant; Sango, Hammadoun Ali et al. (2014) Genetics of low spinal muscular atrophy carrier frequency in sub-Saharan Africa. Ann Neurol 75:525-32
Efthymiou, Anastasia G; Chen, Guibin; Rao, Mahendra et al. (2014) Self-renewal and cell lineage differentiation strategies in human embryonic stem cells and induced pluripotent stem cells. Expert Opin Biol Ther 14:1333-44

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