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MIA Talks

Lineage tracing on transcriptional landscapes links state to fate during differentiation

May 8, 2019
Dept. of Systems Biology, Harvard Medical School

A challenge in stem cell biology is to associate molecular differences among progenitor cells with their capacity to generate mature cell types. Dynamic inference from static snapshots provides some insight, but there are fundamental limits on how well dynamics can be inferred from single-cell transcriptomes alone. Here, we use expressed DNA barcodes to clonally trace single cells during differentiation and apply this approach to the study of hematopoiesis. Our analysis identifies functional boundaries of cell potential early in the hematopoietic hierarchy and locates them on a continuous transcriptional landscape. We use our approach to benchmark methods of dynamic inference from single-cell snapshots, and provide evidence of strong early fate biases dependent on cellular properties hidden from single-cell RNA sequencing.