The effect of Hmga2 GOF/LOF on photoreceptor differentiationThere are few questions regarding retinal development that have intrigued us. First, are retinal progenitor cells (RPCs) irreversibly committed to a certain fate? Using the neurosphere assay we observed that late RPC when cultured in conditions simulating early histogenesis could generate early born neurons (e.g., retinal ganglion cells). With the caveat of in vitro conditions, this observation demonstrates the plasticity inherent in RPCs and suggests that these cells, constrained by older niches, can be rejuvenated for therapeutic purposes. Currently, we are examining small molecule-based rejuvenation of late RPCs.

Second, do RPCs lack self-renewal capacity? If yes, how do we explain the sustenance of these cells over long duration of histogenesis that extends well into the postnatal stages? We observed that RPCs possess self-renewal property, the cardinal feature of stem cells, however, this property, unlike other neural stem cells’, is non-cell autonomous, facilitated by Hmga2, a DNA architectural protein that influences transcriptional regulation in response to cell-cell interactions. Currently, we are examining network regulated by Hmga2 in concert with Lin28 and miRNAs for the maintenance and differentiation of RPCs.  The figure shows the effect of Hmga2 GOF/LOF on photoreceptor differentiation (image: Sowmya Parameswaran)