Biology subjects

Estridge, R. C.

Publications and source records attributed to Estridge, R. C..

2 recordsLinked to original sources

bioRxiv2024

Loss of UBE3A impacts both neuronal and non-neuronal cells in human cerebral organoids

Angelman syndrome is a neurodevelopmental disorder caused by (epi)genetic lesions of maternal UBE3A. Research has focused largely on the role of UBE3A in neurons due to its imprinting in that cell type. Yet, evidence suggests there may be broader neurodevelopmental impacts of UBE3A dysregulation. Human cerebral organoids might reveal these understudied aspects of UBE3A as they recapitulate diverse cell types of the developing human brain. We performed scRNAseq on organoids to reveal the effects of UBE3A disruption on cell type-specific compositions and transcriptomic alterations. In the absence of UBE3A, progenitor proliferation and structures were disrupted while organoid composition shifted away from proliferative cell types. We observed impacts on non-neuronal cells, including choroid plexus enrichment. Furthermore, EMX1+ cortical progenitors were negatively impacted, disrupting corticogenesis, and potentially delaying excitatory neuron maturation. This work reveals novel impacts of UBE3A on understudied cell types and related neurodevelopmental processes and elucidates potential new therapeutic targets. TeaserHuman cerebral organoids exhibit compositional and transcriptomic alterations in both neuronal and non-neuronal cells in the absence of UBE3A.

developmental biology↗

bioRxiv2023

Single cell assessment of human stem cell derived mesolimbic models and their responses to substances of abuse.

The mesolimbic pathway connects ventral tegmental area dopaminergic neurons and striatal medium spiny neurons, playing a critical role in reward and stress behaviors. Exposure to substances of abuse during development and adulthood has been linked to adverse outcomes and molecular changes. The rise of human cell repositories and whole genome sequences enables human functional genomics in a dish, offering insights into human-specific responses to substances of abuse. Characterizations of in vitro models are necessary to ensure appropriate experimental designs and accurate interpretation of results. This study provides a comprehensive characterization of these models and their responses to substances of abuse, introducing new culture conditions for generating medium spiny neurons and dopaminergic neurons from human pluripotent stem cells. Single cell analysis reveals cell type-specific transcriptomic responses to dopamine, cocaine, and morphine, including compound and cell type-specific transcriptomic signatures related to neuroinflammation and alterations in signaling pathways. These findings offer a resource for future genomics studies leveraging human stem cell-derived models. TeaserGeneration and characterization of a novel mesolimbic pathway model and its response to acute dopamine, morphine, and cocaine.

cell biology↗