Profiling intermediate cell states in high resolution

MacLean, Adam L.

doi:10.1016/j.crmeth.2022.100204

Cited by 1 publication

(1 citation statement)

References 15 publications

(17 reference statements)

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“…Consequently, lineage approaches can be used to order cells along differentiation trajectories and to study cell fate decisions ( Luecken and Theis, 2019 ). Recent algorithms that model the dynamics of biological processes use the time-series or even snapshot scRNA-seq data to place the cells in the temporal order of lineage development using their gene expression profiles and also identify the intermediate states which are more plastic in nature and important for fate switches ( Maclean, 2022 ). Hence, using state-of-the-art algorithms of lineage evolution and identifying their high-confidence regulatory genetic drivers is an efficient method for selecting novel candidates contributing toward fate transitions.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional networks of transient cell states during human prefrontal cortex development

Singh

Tiwari

2023

Front. Mol. Neurosci.

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The human brain is divided into various anatomical regions that control and coordinate unique functions. The prefrontal cortex (PFC) is a large brain region that comprises a range of neuronal and non-neuronal cell types, sharing extensive interconnections with subcortical areas, and plays a critical role in cognition and memory. A timely appearance of distinct cell types through embryonic development is crucial for an anatomically perfect and functional brain. Direct tracing of cell fate development in the human brain is not possible, but single-cell transcriptome sequencing (scRNA-seq) datasets provide the opportunity to dissect cellular heterogeneity and its molecular regulators. Here, using scRNA-seq data of human PFC from fetal stages, we elucidate distinct transient cell states during PFC development and their underlying gene regulatory circuitry. We further identified that distinct intermediate cell states consist of specific gene regulatory modules essential to reach terminal fate using discrete developmental paths. Moreover, using in silico gene knock-out and over-expression analysis, we validated crucial gene regulatory components during the lineage specification of oligodendrocyte progenitor cells. Our study illustrates unique intermediate states and specific gene interaction networks that warrant further investigation for their functional contribution to typical brain development and discusses how this knowledge can be harvested for therapeutic intervention in challenging neurodevelopmental disorders.

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Section: Introductionmentioning

confidence: 99%