Pluripotent Stem Cell-Derived Cerebral Organoids Reveal Human Oligodendrogenesis with Dorsal and Ventral Origins

Hyosung Kim, Ranjie Xu, Ragunathan Padmashri, Anna Dunaevsky, Ying Liu, Cheryl F. Dreyfus, Peng Jiang

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

The process of oligodendrogenesis has been relatively well delineated in the rodent brain. However, it remains unknown whether analogous developmental processes are manifested in the human brain. Here we report oligodendrogenesis in forebrain organoids, generated by using OLIG2-GFP knockin human pluripotent stem cell (hPSC)reporter lines. OLIG2/GFP exhibits distinct temporal expression patterns in ventral forebrain organoids (VFOs)versus dorsal forebrain organoids (DFOs). Interestingly, oligodendrogenesis can be induced in both VFOs and DFOs after neuronal maturation. Assembling VFOs and DFOs to generate fused forebrain organoids (FFOs)promotes oligodendroglia maturation. Furthermore, dorsally derived oligodendroglial cells outcompete ventrally derived oligodendroglia and become dominant in FFOs after long-term culture. Thus, our organoid models reveal human oligodendrogenesis with ventral and dorsal origins. These models will serve to study the phenotypic and functional differences between human ventrally and dorsally derived oligodendroglia and to reveal mechanisms of diseases associated with cortical myelin defects.

Original languageEnglish (US)
Pages (from-to)890-905
Number of pages16
JournalStem Cell Reports
Volume12
Issue number5
DOIs
StatePublished - May 14 2019

Keywords

  • OLIG2
  • forebrain organoids
  • fused organoids
  • human pluripotent stem cells
  • oligodendrogenesis
  • oligodendroglial heterogeneity

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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