High-resolution transcriptional landscape of xeno-free human induced pluripotent stem cell-derived cerebellar organoids

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, witho...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Samuel Nayler, Devika Agarwal, Fabiola Curion, Rory Bowden, Esther B. E. Becker
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bef6046921e74ab3991c714a8e11396e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:bef6046921e74ab3991c714a8e11396e
record_format	dspace
spelling	oai:doaj.org-article:bef6046921e74ab3991c714a8e11396e2021-12-02T16:06:09ZHigh-resolution transcriptional landscape of xeno-free human induced pluripotent stem cell-derived cerebellar organoids10.1038/s41598-021-91846-42045-2322https://doaj.org/article/bef6046921e74ab3991c714a8e11396e2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91846-4https://doaj.org/toc/2045-2322Abstract 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.Samuel NaylerDevika AgarwalFabiola CurionRory BowdenEsther B. E. BeckerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Samuel Nayler Devika Agarwal Fabiola Curion Rory Bowden Esther B. E. Becker High-resolution transcriptional landscape of xeno-free human induced pluripotent stem cell-derived cerebellar organoids
description	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.
format	article
author	Samuel Nayler Devika Agarwal Fabiola Curion Rory Bowden Esther B. E. Becker
author_facet	Samuel Nayler Devika Agarwal Fabiola Curion Rory Bowden Esther B. E. Becker
author_sort	Samuel Nayler
title	High-resolution transcriptional landscape of xeno-free human induced pluripotent stem cell-derived cerebellar organoids
title_short	High-resolution transcriptional landscape of xeno-free human induced pluripotent stem cell-derived cerebellar organoids
title_full	High-resolution transcriptional landscape of xeno-free human induced pluripotent stem cell-derived cerebellar organoids
title_fullStr	High-resolution transcriptional landscape of xeno-free human induced pluripotent stem cell-derived cerebellar organoids
title_full_unstemmed	High-resolution transcriptional landscape of xeno-free human induced pluripotent stem cell-derived cerebellar organoids
title_sort	high-resolution transcriptional landscape of xeno-free human induced pluripotent stem cell-derived cerebellar organoids
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/bef6046921e74ab3991c714a8e11396e
work_keys_str_mv	AT samuelnayler highresolutiontranscriptionallandscapeofxenofreehumaninducedpluripotentstemcellderivedcerebellarorganoids AT devikaagarwal highresolutiontranscriptionallandscapeofxenofreehumaninducedpluripotentstemcellderivedcerebellarorganoids AT fabiolacurion highresolutiontranscriptionallandscapeofxenofreehumaninducedpluripotentstemcellderivedcerebellarorganoids AT rorybowden highresolutiontranscriptionallandscapeofxenofreehumaninducedpluripotentstemcellderivedcerebellarorganoids AT estherbebecker highresolutiontranscriptionallandscapeofxenofreehumaninducedpluripotentstemcellderivedcerebellarorganoids
_version_	1718385112404459520

High-resolution transcriptional landscape of xeno-free human induced pluripotent stem cell-derived cerebellar organoids

Ejemplares similares