4.6 Article

PAX6-positive microglia evolve locally in hiPSC-derived ocular organoids

Journal

STEM CELL REPORTS
Volume 17, Issue 2, Pages 221-230

Publisher

CELL PRESS
DOI: 10.1016/j.stemcr.2021.12.009

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Funding

  1. AMED [20gm1210004]
  2. JSPS KAKENHI [JP17K11475]
  3. Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University

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The study found that cells with characteristics resembling microglia naturally develop in eye-like SEAM organoids derived from human-induced pluripotent stem cells. These unique cells are PAX6-positive and possess some mesoderm characteristics.
Microglia are the resident immune cells of the central nervous system (CNS). They govern the immunogenicity of the retina, which is considered to be part of the CNS; however, it is not known how microglia develop in the eye. Here, we studied human-induced pluripotent stem cells (hiPSCs) that had been expanded into a self-formed ectodermal autonomous multi-zone (SEAM) of cells that partially mimics human eye development. Our results indicated that microglia-like cells, which have characteristics of yolk-sac-like linage cells, naturally develop in 2D eye-like SEAM organoids, which lack any vascular components. These cells are unique in that they are paired box protein 6 (PAX6)-positive, yet they possess some characteristics of mesoderm. Collectively, the data support the notion of the existence of an isolated, locally developing immune system in the eye, which is independent of the body's vasculature and general immune system.

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