Transcriptomics

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Lineage tracing on transcriptional landscapes links state to fate during differentiation


ABSTRACT: A challenge in biology is to associate molecular differences among progenitor cells with their capacity to generate mature cell types. Here, we use expressed DNA barcodes to clonally trace transcriptomes over time, applied to study fate determination in hematopoiesis. We identify states of primed fate potential, and locate them on a continuous transcriptional landscape. We identify two routes of monocyte differentiation that leave an imprint on mature cells. Clonal analysis also reveals fate biases into multiple lineages that depend on stable cellular properties hidden from single-cell RNA sequencing. Finally, we benchmark computational methods of dynamic inference from single-cell snapshots, showing that fate choice occurs earlier than is detected by state-of the-art algorithms, and that cells progress steadily through pseudotime with precise and consistent dynamics.

ORGANISM(S): Mus musculus

PROVIDER: GSE140802 | GEO | 2019/11/22

REPOSITORIES: GEO

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