Rapid and Efficient Generation of Myelinating Human Oligodendrocytes in Organoids

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.

Automated summary

A protocol has been developed to generate brain organoids containing myelinating oligodendrocytes, cortical neuronal cells, and astrocytes within 42 days from human pluripotent stem cells. These organoids serve as a valuable platform for studying neurological diseases and drug screening for white matter diseases.