Differential growth and transcriptomic profile of stem cell-derived midbrain astrocytes

Li, Zongze ORCID: https://orcid.org/0000-0002-9923-7205, Fernandez Cardo, Lucia, Rokicki, Michal, Monzon Sandoval, Jimena, Volpato, Viola, Wessely, Frank, Webber, Caleb ORCID: https://orcid.org/0000-0001-8063-7674 and Li, Meng ORCID: https://orcid.org/0000-0002-4803-4643 2024. Differential growth and transcriptomic profile of stem cell-derived midbrain astrocytes. eLife 13 , RP96423. 10.7554/eLife.96423.1

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Abstract

Regional specificity of stem cell-derived astrocytes is believed to be an important prerequisite for their applications in disease modelling and cell-based therapies. The regional identity of these astrocytes is often defined by the positional characteristics of their antecedent, stem cell-derived neural progenitors patterned to a fate of interest, with the assumption that the positional specification is to be preserved by the derived astrocytes. Using a human induced pluripotent stem cell line designed for tracing midbrain floor plate derivatives, here we show that lineage composition of the derived astrocytes is not a faithful recapitulation of the founder progenitor population, as demonstrated by the loss of floor plate differentiated progeny in the final astrocyte products. Using deep single cell RNA sequencing, we identified distinct transcriptomic signatures of midbrain floor plate-derived astrocytes. Our study highlights the need for rigorous characterisation of pluripotent stem cell-derived regional astrocytes and provides a valuable resource for assessing midbrain floor plate-derived human astrocytes.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Advanced Research Computing @ Cardiff (ARCCA) MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Medicine Neuroscience and Mental Health Research Institute (NMHRI)
Publisher:	eLife Sciences Publications
ISSN:	2050-084X
Funders:	MRC
Date of First Compliant Deposit:	28 February 2024
Date of Acceptance:	27 February 2024
Last Modified:	20 Nov 2024 15:02
URI:	https://orca.cardiff.ac.uk/id/eprint/166613

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