Hmga2 regulates self-renewal of retinal progenitors

Sowmya Parameswaran, Xiaohuan Xia, Ganapati Hegde, Iqbal Ahmad

Research output: Contribution to journalArticle

26 Scopus citations

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 languageEnglish (US)
Pages (from-to)4087-4097
Number of pages11
JournalDevelopment (Cambridge)
Volume141
Issue number21
DOIs
StatePublished - Nov 1 2014

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Keywords

  • Epigenetic
  • Hmga2
  • Progenitors
  • Rat
  • Retina
  • Self-renewal
  • Stem cells

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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