Modeling early retinal development with human embryonic and induced pluripotent stem cells

JS Meyer, RL Shearer, EE Capowski… - Proceedings of the …, 2009 - National Acad Sciences
JS Meyer, RL Shearer, EE Capowski, LS Wright, KA Wallace, EL McMillan, SC Zhang…
Proceedings of the National Academy of Sciences, 2009National Acad Sciences
Human pluripotent stem cells have the potential to provide comprehensive model systems
for the earliest stages of human ontogenesis. To serve in this capacity, these cells must
undergo a targeted, stepwise differentiation process that follows a normal developmental
timeline. Here we demonstrate the ability of both human embryonic stem cells (hESCs) and
induced pluripotent stem (iPS) cells to meet these requirements for human retinogenesis.
Upon differentiation, hESCs initially yielded a highly enriched population of early eye field …
Human pluripotent stem cells have the potential to provide comprehensive model systems for the earliest stages of human ontogenesis. To serve in this capacity, these cells must undergo a targeted, stepwise differentiation process that follows a normal developmental timeline. Here we demonstrate the ability of both human embryonic stem cells (hESCs) and induced pluripotent stem (iPS) cells to meet these requirements for human retinogenesis. Upon differentiation, hESCs initially yielded a highly enriched population of early eye field cells. Thereafter, a subset of cells acquired features of advancing retinal differentiation in a sequence and time course that mimicked in vivo human retinal development. Application of this culture method to a human iPS cell line also generated retina-specific cell types at comparable times in vitro. Lastly, altering endogenous signaling during differentiation affected lineage-specific gene expression in a manner consistent with established mechanisms of early neural and retinal cell fate determination. These findings should aid in the investigation of the molecular events governing retinal specification from human pluripotent stem cells.
National Acad Sciences