Vlot, A. H. C. | Search bioRxiv

bioRxiv2020

SEMITONES: Single-cEll Marker IdentificaTiON by Enrichment Scoring

Identification of markers is an essential step in single-cell analytic. Current marker identification strategies typically rely on cluster assignments of cells. Cluster assignment, in particular of development data, is non-trivial, potentially arbitrary and commonly relies on prior knowledge. Yet, cluster uncertainty is not commonly taken into account. In response, we present SEMITONES, a principled method for cluster-free marker identification. We showcase its application on healthy haematopoiesis data as 1) a robust alternative to highly variable gene selection, 2) for marker gene and regulatory region identification, and 3) for the construction of co-enrichment networks that reveal regulators of cell identity.

systems biology↗

bioRxiv2020

A single cell Arabidopsis root atlas reveals developmental trajectories in wild type and cell identity mutants

SummaryCell fate acquisition is a fundamental developmental process in all multicellular organisms. Yet, much is unknown regarding how a cell traverses the pathway from stem cell to terminal differentiation. Advances in single cell genomics1 hold promise for unraveling developmental mechanisms2–3 in tissues4, organs5–6, and organisms7–8. However, lineage tracing can be challenging for some tissues9 and integration of high-quality datasets is often necessary to detect rare cell populations and developmental states10,11. Here, we harmonized single cell mRNA sequencing data from over 110,000 cells to construct a comprehensive atlas for a stereotypically developing organ with indeterminate growth, the Arabidopsis root. To test the utility of the atlas to interpret new datasets, we profiled mutants for two key transcriptional regulators at single cell resolution, shortroot and scarecrow. Although both transcription factors are required for early specification of cell identity12, our results suggest the existence of an alternative pathway acting in mature cells to specify endodermal identity, for which SHORTROOT is required. Uncovering the architecture of this pathway will provide insight into specification and stabilization of the endodermis, a tissue analogous to the mammalian epithelium. Thus, the atlas is a pivotal advance for unraveling the transcriptional programs that specify and maintain cell identity to regulate organ development in space and time.Competing Interest StatementPNB is the co-founder and Chair of the Scientific Advisory Board of Hi Fidelity Genetics, Inc, a company that works on crop root growth.View Full Text

plant biology↗