Uzquiano A, Kedaigle AJ, Pigoni M, Paulsen B, Adiconis X, Kim K, Faits T, Nagaraja S, Antón-Bolaños N, Gerhardinger C, Tucewicz A, Murray E, Jin X, Buenrostro J, Chen F, Velasco S, Regev A, Levin JZ, Arlotta P. 2022. Proper acquisition of cell class identity in organoids allows definition of fate specification programs of the human cerebral cortex. Cell. 185(20):3770-3788.e27. Pubmed: 36179669 DOI:S0092-8674(22)01168-0


Realizing the full utility of brain organoids to study human development requires understanding whether organoids precisely replicate endogenous cellular and molecular events, particularly since acquisition of cell identity in organoids can be impaired by abnormal metabolic states. We present a comprehensive single-cell transcriptomic, epigenetic, and spatial atlas of human cortical organoid development, comprising over 610,000 cells, from generation of neural progenitors through production of differentiated neuronal and glial subtypes. We show that processes of cellular diversification correlate closely to endogenous ones, irrespective of metabolic state, empowering the use of this atlas to study human fate specification. We define longitudinal molecular trajectories of cortical cell types during organoid development, identify genes with predicted human-specific roles in lineage establishment, and uncover early transcriptional diversity of human callosal neurons. The findings validate this comprehensive atlas of human corticogenesis in vitro as a resource to prime investigation into the mechanisms of human cortical development.
Copyright © 2022 Elsevier Inc. All rights reserved.

Related Faculty

Photo of Jason Buenrostro

The Buenrostro lab is broadly dedicated to advancing our knowledge of gene regulation and the downstream consequences on cell fate decisions.

Photo of Paola Arlotta

Dr. Arlotta is interested in understanding the molecular laws that govern the birth, differentiation and assembly of the cerebral cortex, the part of the brain that controls how we sense, move and think. She integrates developmental and evolutionary knowledge to investigate therapies for brain repair and for modeling neuropsychiatric disease.

Search Menu