Abstract
In vertebrate retina, histogenesis occurs over an extended period. To sustain the temporal generation of diverse cell types, retinal progenitor cells (RPCs) must self-renew. However, self-renewal and regulation of RPCs remain poorly understood. Here, we demonstrate that cellextrinsic factors coordinate with the epigenetic regulator high-mobility group AT-hook 2 (Hmga2) to regulate self-renewal of late retinal progenitor cells (RPCs).We observed that a small subset of RPCswas capable of clonal propagation and retained multipotentiality of parents in the presence of endothelial cells (ECs), known self-renewal regulators in various stem cell niches. The self-renewing effects, also observed in vivo, involve multiple intercellular signaling pathways, engaging Hmga2. As progenitors exhaust during retinal development, expression of Hmga2 progressively decreases. Analyses of Hmga2- expression perturbation, in vitro and in vivo, revealed that Hmga2 functionally helps to mediate cell-extrinsic influences on late-retinal progenitor self-renewal. Our results provide a framework for integrating the diverse intercellular influences elicited by epigenetic regulators for self-renewal in a dynamic stem cell niche: the developing vertebrate retina.
Original language | English (US) |
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Pages (from-to) | 4087-4097 |
Number of pages | 11 |
Journal | Development (Cambridge) |
Volume | 141 |
Issue number | 21 |
DOIs | |
State | Published - Nov 1 2014 |
Keywords
- Epigenetic
- Hmga2
- Progenitors
- Rat
- Retina
- Self-renewal
- Stem cells
ASJC Scopus subject areas
- Molecular Biology
- Developmental Biology