Deconstructing Olfactory Stem Cell Trajectories at Single Cell Resolution
Cell Stem Cell, 2017
Russell B. Fletcher*, Diya Das*, Levi Gadye, Kelly N. Street, Ariane Baudhuin, Allon Wagner, Michael B. Cole, Quetzal Flores, Yoon Gi Choi, Nir Yosef, Elizabeth Purdom, Sandrine Dudoit, Davide Risso and John Ngai. (2017). Deconstructing Olfactory Stem Cell Trajectories at Single Cell Resolution. Cell Stem Cell 20, 817-830.e8. http://www.cell.com/cell-stem-cell/fulltext/S1934-5909(17)30127-3
Abstract
A detailed understanding of the paths that stem cells traverse to generate mature progeny is vital for elucidating the mechanisms governing cell fate decisions and tissue homeostasis. Adult stem cells maintain and regenerate multiple mature cell lineages in the olfactory epithelium. Here we integrate single-cell RNA sequencing and robust statistical analyses with in vivo lineage tracing to define a detailed map of the postnatal olfactory epithelium, revealing cell fate potentials and branchpoints in olfactory stem cell lineage trajectories. Olfactory stem cells produce support cells via direct fate conversion in the absence of cell division, and their multipotency at the population level reflects collective unipotent cell fate decisions by single stem cells. We further demonstrate that Wnt signaling regulates stem cell fate by promoting neuronal fate choices. This integrated approach reveals the mechanisms guiding olfactory lineage trajectories and provides a model for deconstructing similar hierarchies in other stem cell niches.
Data and Code
The GEO accession number for the RNA-sequencing data reported in this paper is GSE95601.
The code can be found at https://github.com/rufletch/p63-HBC-diff.
Press Release
A press release is available from the UC Berkeley News Center