Rapid and Efficient Generation of Myelinating Human Oligodendrocytes in Organoids

Mohammed R Shaker; Giovanni Pietrogrande; Sally Martin; Ju-Hyun Lee; Woong Sun; Ernst J Wolvetang

doi:10.3389/fncel.2021.631548

Rapid and Efficient Generation of Myelinating Human Oligodendrocytes in Organoids

Front Cell Neurosci. 2021 Mar 17:15:631548. doi: 10.3389/fncel.2021.631548. eCollection 2021.

Authors

Mohammed R Shaker¹, Giovanni Pietrogrande¹, Sally Martin^{1

2}, Ju-Hyun Lee³, Woong Sun³, Ernst J Wolvetang¹

Affiliations

¹ Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, Australia.
² School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, Australia.
³ Department of Anatomy, Brain Korea 21 Plus Program for Biomedical Science, Korea University College of Medicine, Seoul, South Korea.

Abstract

Human stem cell derived brain organoids are increasingly gaining attention as an ideal model system for investigating neurological diseases, particularly those that involve myelination defects. However, current protocols for generating brain organoids with sufficiently mature oligodendrocytes that deposit myelin on endogenously produced neurons are lengthy and complicated. Taking advantage of a human pluripotent stem cell line that reports on SOX10 expression, we developed a protocol that involves a 42 day exposure of neuroectoderm-derived organoids to a cocktail of growth factors and small molecules that collectively foster oligodendrocyte specification and survival. Importantly, the resulting day 42 brain organoids contain both myelinating oligodendrocytes, cortical neuronal cells and astrocytes. These oligodendrocyte brain organoids therefore constitute a valuable and tractable platform for functional neurogenomics and drug screening for white matter diseases.

Keywords: induced pluripotent stem cells; myelination; oligodendrocyte; organoid; reporter cell line.