Details

Autor(en) / Beteiligte

• Brandt, Emma Becky

Titel

Dysregulation of P53 during Cardiac Differentiation of Human Induced Pluripotent Stem Cells

Ort / Verlag

ProQuest Dissertations & Theses

Erscheinungsjahr

2018

Link zum Volltext

• ProQuest

Quelle

ProQuest Dissertations & Theses A&I

Beschreibungen/Notizen

• Congenital heart defects represent the most common birth defects seen in infants, but only 15–20% of these defects have known genetic causes. Most congenital heart defects are attributed to interplay between genetics and the environment. Thus, it is critical to determine how the developing heart responds to stressful stimuli so we have better insights into how congenital heart defects arise and derive new therapies for treatment. This thesis highlights the importance of understanding how different stages of cardiogenesis respond to stress signaling modulators such as p53 and their subsequent contribution to the pathogenesis of congenital heart defects. Chapter 1 reviews the current knowledge of p53 activity in heart development, the adult heart, and in cardiac differentiation of pluripotent stem cells. Chapter II summarizes the materials and methods utilized in these studies. Chapter III characterizes the expression levels and localization of p53 during human cardiac differentiation of induced pluripotent stem cells. Chapter IV reveals differential stage-specific responses to p53 activation during cardiac differentiation and uncovers a new potential role for p53 in cardiomyocyte redox metabolism. Chapter V highlights p53’s role in the disease pathogenesis of a proband with Hypoplastic Left Heart Syndrome. Chapter VI summarizes and expands on the results of this thesis and discusses further experimentation regarding p53’s biology in the developing heart.