Hmga2 regulates self-renewal of retinal progenitors

Sowmya Parameswaran, Xiaohuan Xia, Ganapati Hegde, Iqbal Ahmad

Research output: Contribution to journalArticlepeer-review

29 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

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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