High-resolution transcriptional landscape of xeno-free human induced pluripotent stem cell-derived cerebellar organoids
- Author(s)
- Nayler, S; Agarwal, D; Curion, F; Bowden, R; Becker, EBE;
- Details
- Publication Year 2021-06-21,Volume 11,Issue #1,Page 12959
- Journal Title
- Scientific Reports
- Abstract
- Current protocols for producing cerebellar neurons from human pluripotent stem cells (hPSCs) often rely on animal co-culture and mostly exist as monolayers, limiting their capability to recapitulate the complex processes in the developing cerebellum. Here, we employed a robust method, without the need for mouse co-culture to generate three-dimensional cerebellar organoids from hPSCs that display hallmarks of in vivo cerebellar development. Single-cell profiling followed by comparison to human and mouse cerebellar atlases revealed the presence and maturity of transcriptionally distinct populations encompassing major cerebellar cell types. Encapsulation with Matrigel aimed to provide more physiologically-relevant conditions through recapitulation of basement-membrane signalling, influenced both growth dynamics and cellular composition of the organoids, altering developmentally relevant gene expression programmes. We identified enrichment of cerebellar disease genes in distinct cell populations in the hPSC-derived cerebellar organoids. These findings ascertain xeno-free human cerebellar organoids as a unique model to gain insight into cerebellar development and its associated disorders.
- Research Division(s)
- Advanced Technology And Biology
- PubMed ID
- 34155230
- Publisher's Version
- https://doi.org/10.1038/s41598-021-91846-4
- Open Access at Publisher's Site
https://doi.org/ 10.1038/s41598-021-91846-4- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2021-06-25 01:41:43
Last Modified: 2021-11-09 11:20:59