Midbrain-like Organoids from Human Pluripotent Stem Cells Contain Functional Dopaminergic and Neuromelanin-Producing Neurons

Junghyun Jo, Yixin Xiao, Alfred Xuyang Sun, Engin Cukuroglu, Hoang Dai Tran, Jonathan Göke, Zi Ying Tan, Tzuen Yih Saw, Cheng Peow Tan, Hidayat Lokman, Younghwan Lee, Donghoon Kim, Han Seok Ko, Seong Oh Kim, Jae Hyeon Park, Nam Joon Cho, Thomas M. Hyde, Joel E. Kleinman, Joo Heon Shin, Daniel R. WeinbergerEng King Tan, Hyunsoo Shawn Je, Huck Hui Ng

Research output: Contribution to journalArticlepeer-review

Abstract

Recent advances in 3D culture systems have led to the generation of brain organoids that resemble different human brain regions; however, a 3D organoid model of the midbrain containing functional midbrain dopaminergic (mDA) neurons has not been reported. We developed a method to differentiate human pluripotent stem cells into a large multicellular organoid-like structure that contains distinct layers of neuronal cells expressing characteristic markers of human midbrain. Importantly, we detected electrically active and functionally mature mDA neurons and dopamine production in our 3D midbrain-like organoids (MLOs). In contrast to human mDA neurons generated using 2D methods or MLOs generated from mouse embryonic stem cells, our human MLOs produced neuromelanin-like granules that were structurally similar to those isolated from human substantia nigra tissues. Thus our MLOs bearing features of the human midbrain may provide a tractable in vitro system to study the human midbrain and its related diseases.

Original languageEnglish (US)
Pages (from-to)248-257
Number of pages10
JournalCell stem cell
Volume19
Issue number2
DOIs
StatePublished - Aug 4 2016

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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