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Exploratory Studies of Induced Pluripotent Stem (iPS) Cells from Healthy and Patient Populations

NAMHC Concept Clearance


David Panchision, Ph.D.
Chief, Developmental Neurobiology Program
Molecular, Cellular & Genomic Neuroscience Research Branch
Division of Neuroscience and Basic Behavioral Science


This initiative will support exploratory studies to generate and characterize induced pluripotent stem (iPS) cells from healthy and/or patient populations.


The study of thought, mood and social disorders currently suffers from a gap in understanding basic molecular and developmental defects that occur at the cellular level. The ability to generate tractable animal models, which could address this gap, is hindered by the absence of an obvious human lesion or single gene defect that can be replicated in animals. The recent development of induced pluripotent stem (iPS) cells may provide a unique opportunity to resolve this experimental dilemma. iPS cells are similar to embryonic stem (ES) cells in that they exhibit pluripotency, the ability to generate all body cell types – including neurons and glia. However, they differ from ES cells in that somatic cells from an adult can be readily induced to pluripotency by in vitro genetic manipulation, thereby generating an individualized tool to study (and perhaps eventually treat) a patient’s disorder. We propose to support exploratory studies to generate iPS cells from human control and/or patient populations with cognitive/affective/social disorders, particularly those in which a genetic linkage has been inferred. For this relatively new area, it is recognized that the scientific community is essentially in the discovery phase and there is substantial basic research that remains to be done. An emphasis should be placed on appropriate validation of iPS cells and their derivatives (as with ES cells), evaluating the hetero/homogeneity of cell populations to be screened and comparison of results with predicted biological outcomes relevant to brain function and mental disorders. These studies will provide novel insights into neuronal and glial development and function in control and patient populations, which can bridge the gap between animal models and the clinical manifestations of mental disorders.

Studies can include:

  • Techniques to improve or maximize iPS cell differentiation to cells of interest (e.g. dopaminergic, GABAergic, glutamatergic neurons).
  • Differences in the developmental trajectory of neuronal and glial differentiation from iPS cells of human control versus psychiatric patient populations.
  • Pharmacological and electrophysiological characterization of iPS cell derivatives.
  • Genomic, epigenomic, proteomic profiling of iPS cell derivatives, including neural progenitors, neuronal and/or non-neuronal cell types.

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