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

Mohammed R. Shaker, Giovanni Pietrogrande, Sally Martin, Ju Hyun Lee, Woong Sun, Ernst J. Wolvetang

Department of Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

33 Citations (Scopus)

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.

Original language	English
Article number	631548
Journal	Frontiers in Cellular Neuroscience
Volume	15
DOIs	https://doi.org/10.3389/fncel.2021.631548
Publication status	Published - 2021 Mar 17

Bibliographical note

Funding Information:
Bruce Conklin (Department of Medicine Gladstone Institute of Cardiovascular Disease) is greatly acknowledged for providing the original WTC iPSC. The authors acknowledge the facilities, and the scientific and technical assistance, of the Microscopy Australia Facility at the Center for Microscopy and Microanalysis (CMM) of The University of Queensland. This work was performed in part at the Queensland node of the Australian National Fabrication Facility, a company established under the National Collaborative Research Infrastructure Strategy to provide nano- and micro-fabrication facilities for Australia's researchers. Funding. MS and GP are supported by the Medical Research Future Fund- Accelerated Research, Leukodystrophy flagship Massimo's Mission EPCD000034. SM is supported by the Perry Cross Spinal Research Foundation. EW is supported by the Australian National Health and Medical Research Council (applications 1138795, 1127976, 1144806, and 1130168), BrAshA-T foundation, Perry Cross Spinal Research Foundation and the Australian Research Council.

Funding Information:
MS and GP are supported by the Medical Research Future Fund-Accelerated Research, Leukodystrophy flagship Massimo’s Mission EPCD000034. SM is supported by the Perry Cross Spinal Research Foundation. EW is supported by the Australian National Health and Medical Research Council (applications 1138795, 1127976, 1144806, and 1130168), BrAshA-T foundation, Perry Cross Spinal Research Foundation and the Australian Research Council.

Publisher Copyright:
© Copyright © 2021 Shaker, Pietrogrande, Martin, Lee, Sun and Wolvetang.

Keywords

induced pluripotent stem cells
myelination
oligodendrocyte
organoid
reporter cell line

ASJC Scopus subject areas

Cellular and Molecular Neuroscience

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3389/fncel.2021.631548

Cite this

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title = "Rapid and Efficient Generation of Myelinating Human Oligodendrocytes in Organoids",

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.",

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author = "Shaker, {Mohammed R.} and Giovanni Pietrogrande and Sally Martin and Lee, {Ju Hyun} and Woong Sun and Wolvetang, {Ernst J.}",

note = "Funding Information: Bruce Conklin (Department of Medicine Gladstone Institute of Cardiovascular Disease) is greatly acknowledged for providing the original WTC iPSC. The authors acknowledge the facilities, and the scientific and technical assistance, of the Microscopy Australia Facility at the Center for Microscopy and Microanalysis (CMM) of The University of Queensland. This work was performed in part at the Queensland node of the Australian National Fabrication Facility, a company established under the National Collaborative Research Infrastructure Strategy to provide nano- and micro-fabrication facilities for Australia's researchers. Funding. MS and GP are supported by the Medical Research Future Fund- Accelerated Research, Leukodystrophy flagship Massimo's Mission EPCD000034. SM is supported by the Perry Cross Spinal Research Foundation. EW is supported by the Australian National Health and Medical Research Council (applications 1138795, 1127976, 1144806, and 1130168), BrAshA-T foundation, Perry Cross Spinal Research Foundation and the Australian Research Council. Funding Information: MS and GP are supported by the Medical Research Future Fund-Accelerated Research, Leukodystrophy flagship Massimo{\textquoteright}s Mission EPCD000034. SM is supported by the Perry Cross Spinal Research Foundation. EW is supported by the Australian National Health and Medical Research Council (applications 1138795, 1127976, 1144806, and 1130168), BrAshA-T foundation, Perry Cross Spinal Research Foundation and the Australian Research Council. Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2021 Shaker, Pietrogrande, Martin, Lee, Sun and Wolvetang.",

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N1 - Funding Information: Bruce Conklin (Department of Medicine Gladstone Institute of Cardiovascular Disease) is greatly acknowledged for providing the original WTC iPSC. The authors acknowledge the facilities, and the scientific and technical assistance, of the Microscopy Australia Facility at the Center for Microscopy and Microanalysis (CMM) of The University of Queensland. This work was performed in part at the Queensland node of the Australian National Fabrication Facility, a company established under the National Collaborative Research Infrastructure Strategy to provide nano- and micro-fabrication facilities for Australia's researchers. Funding. MS and GP are supported by the Medical Research Future Fund- Accelerated Research, Leukodystrophy flagship Massimo's Mission EPCD000034. SM is supported by the Perry Cross Spinal Research Foundation. EW is supported by the Australian National Health and Medical Research Council (applications 1138795, 1127976, 1144806, and 1130168), BrAshA-T foundation, Perry Cross Spinal Research Foundation and the Australian Research Council. Funding Information: MS and GP are supported by the Medical Research Future Fund-Accelerated Research, Leukodystrophy flagship Massimo’s Mission EPCD000034. SM is supported by the Perry Cross Spinal Research Foundation. EW is supported by the Australian National Health and Medical Research Council (applications 1138795, 1127976, 1144806, and 1130168), BrAshA-T foundation, Perry Cross Spinal Research Foundation and the Australian Research Council. Publisher Copyright: © Copyright © 2021 Shaker, Pietrogrande, Martin, Lee, Sun and Wolvetang.

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KW - reporter cell line

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Rapid and Efficient Generation of Myelinating Human Oligodendrocytes in Organoids

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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