Single-cell multimodal transcriptomics to study neuronal diversity in human stem cell-derived brain tissue and organoid models

Abstract

Advances in human cell reprogramming and induced pluripotent stem cell technologies generate tremendous potential for neuroscience studies in health and disease, while the neuroscientist toolbox for engineering a range of brain tissues and neuronal cell types is rapidly expanding. Here, we discuss how the emergence of new single-cell genomics methods may help benchmarking and optimizing the tissue engineering process. The inherent heterogeneity and variability of reprogrammed brain tissue may conceal important disease mechanisms if not accounted for by rigorous experimental design. Single-cell genomics methods may address this technical challenge and ultimately improve the development of new therapeutics for neurological and psychiatric disorders.

Keywords: Brain organoids; Cellular heterogeneity; Human neuron transcriptome; Induced pluripotent stem cell (iPSC); Neuronal tissue; Single-cell RNA-seq; Single-cell multimodal genomics.