Modeling Developmental Brain Diseases Using Human Pluripotent Stem Cells-Derived Brain Organoids - Progress and Perspective

Afrin Bhattacharya; Wendy W Y Choi; Julien Muffat; Yun Li

doi:10.1016/j.jmb.2021.167386

Modeling Developmental Brain Diseases Using Human Pluripotent Stem Cells-Derived Brain Organoids - Progress and Perspective

J Mol Biol. 2022 Feb 15;434(3):167386. doi: 10.1016/j.jmb.2021.167386. Epub 2021 Dec 6.

Authors

Afrin Bhattacharya¹, Wendy W Y Choi², Julien Muffat³, Yun Li⁴

Affiliations

¹ Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G 0A4, Canada; The University of Toronto, Department of Molecular Genetics, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
² Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G 0A4, Canada; The University of Toronto, Department of Molecular Genetics, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Program in Genetics and Genome Biology, The Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G 0A4, Canada.
³ Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G 0A4, Canada; The University of Toronto, Department of Molecular Genetics, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Program in Neurosciences and Mental Health, The Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G 0A4, Canada.
⁴ Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G 0A4, Canada; The University of Toronto, Department of Molecular Genetics, 1 King's College Circle, Toronto, ON M5S 1A8, Canada. Electronic address: yun.li@sickkids.ca.

PMID: 34883115
DOI: 10.1016/j.jmb.2021.167386

Abstract

Developmental brain diseases encompass a group of conditions resulting from genetic or environmental perturbations during early development. Despite the increased research attention in recent years following recognition of the prevalence of these diseases, there is still a significant lack of knowledge of their etiology and treatment options. The genetic and clinical heterogeneity of these diseases, in addition to the limitations of experimental animal models, contribute to this difficulty. In this regard, the advent of brain organoid technology has provided a new means to study the cause and progression of developmental brain diseases in vitro. Derived from human pluripotent stem cells, brain organoids have been shown to recapitulate key developmental milestones of the early human brain. Combined with technological advancements in genome editing, tissue engineering, electrophysiology, and multi-omics analysis, brain organoids have expanded the frontiers of human neurobiology, providing valuable insight into the cellular and molecular mechanisms of normal and pathological brain development. This review will summarize the current progress of applying brain organoids to model human developmental brain diseases and discuss the challenges that need to be overcome to further advance their utility.

Keywords: brain; development; disorder; organoids; technology.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Brain Diseases* / embryology
Brain* / abnormalities
Cell Culture Techniques
Humans
Organoids* / abnormalities
Pluripotent Stem Cells*