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bioRxiv · 10.1101/2024.01.22.575551

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

Li, Z.·Cardo, L. F.·Rokicki, M.·Monzon-Sandoval, J.·Volpato, V.·Wessely, F.·Webber, C.·Li, M.
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Abstract

The regional specificity of stem cell-derived astrocytes is believed to be an important prerequisite for their application in disease modelling and cell-based therapies. Due to the lack of subtype-defining markers for astrocytes in different regions of the brain, the regional identity of in vitro-derived astrocytes is often declared by the dominant positional characteristics of their antecedent neural progenitors, patterned to a fate of interest, with the assumption that the positional trait is preserved by the derived astrocytes via linear descent. Using a human induced pluripotent stem cell line designed for tracing derivatives of LMX1A+ cells combined with a ventral midbrain induction paradigm, we show that astrocytes originating from LMX1A+ progenitors can only be generated if these progenitors are purified prior to the astrocyte differentiation process, or their progenies are gradually lost to progenies of LMX1A- progenitors. This finding indicates that the lineage composition of iPSC-derived astrocytes may not accurately recapitulate the founder progenitor population. Using deep single-cell RNA sequencing, we identified distinct transcriptomic signatures in astrocytes derived from the LMX1A+ progenitor cells. Our study highlights the need for rigorous characterization of pluripotent stem cell-derived regional astrocytes, and provides a resource for assessing LMX1A+ ventral midbrain progenitor-derived human astrocytes.

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Li, Z., Cardo, L. F., Rokicki, M., Monzon-Sandoval, J., Volpato, V., Wessely, F., Webber, C., Li, M.. 2024-01-22. Differential growth and transcriptomic profile in stem cell-derived midbrain astrocytes. https://doi.org/10.1101/2024.01.22.575551

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