Regeneration associated transcriptional signature of retinal microglia and macrophages

Sci Rep. 2019 Mar 18;9(1):4768. doi: 10.1038/s41598-019-41298-8.

Abstract

Zebrafish have the remarkable capacity to regenerate retinal neurons following a variety of damage paradigms. Following initial tissue insult and a period of cell death, a proliferative phase ensues that generates neuronal progenitors, which ultimately regenerate damaged neurons. Recent work has revealed that Müller glia are the source of regenerated neurons in zebrafish. However, the roles of another important class of glia present in the retina, microglia, during this regenerative phase remain elusive. Here, we examine retinal tissue and perform QuantSeq. 3'mRNA sequencing/transcriptome analysis to reveal localization and putative functions, respectively, of mpeg1 expressing cells (microglia/macrophages) during Müller glia-mediated regeneration, corresponding to a time of progenitor proliferation and production of new neurons. Our results indicate that in this regenerative state, mpeg1-expressing cells are located in regions containing regenerative Müller glia and are likely engaged in active vesicle trafficking. Further, mpeg1+ cells congregate at and around the optic nerve head. Our transcriptome analysis reveals several novel genes not previously described in microglia. This dataset represents the first report, to our knowledge, to use RNA sequencing to probe the microglial transcriptome in such context, and therefore provides a resource towards understanding microglia/macrophage function during successful retinal (and central nervous tissue) regeneration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cell Differentiation / physiology
  • Cell Proliferation
  • Ependymoglial Cells / cytology*
  • Gene Expression Profiling
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Microglia / cytology*
  • Nerve Regeneration / physiology*
  • Neural Stem Cells / cytology*
  • Retina / cytology
  • Retinal Neurons / cytology*
  • Retinal Neurons / physiology
  • Zebrafish
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism

Substances

  • Membrane Proteins
  • Zebrafish Proteins
  • mpeg1.1 protein, zebrafish