Deconstructing Olfactory Stem Cell Trajectories at Single-Cell Resolution

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; John Ngai

doi:10.1016/j.stem.2017.04.003

Deconstructing Olfactory Stem Cell Trajectories at Single-Cell Resolution

Cell Stem Cell. 2017 Jun 1;20(6):817-830.e8. doi: 10.1016/j.stem.2017.04.003. Epub 2017 May 11.

Authors

Russell B Fletcher¹, Diya Das¹, Levi Gadye², Kelly N Street³, Ariane Baudhuin¹, Allon Wagner⁴, Michael B Cole⁵, Quetzal Flores¹, Yoon Gi Choi⁶, Nir Yosef⁴, Elizabeth Purdom⁷, Sandrine Dudoit⁸, Davide Risso⁹, John Ngai¹⁰

Affiliations

¹ Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
² Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720, USA.
³ Division of Biostatistics, University of California, Berkeley, CA 94720, USA; Center for Computational Biology, University of California, Berkeley, CA 94720, USA.
⁴ Department of Electrical Engineering and Computer Science, University of California, Berkeley, CA 94720, USA; Center for Computational Biology, University of California, Berkeley, CA 94720, USA.
⁵ Department of Physics, University of California, Berkeley, CA 94720, USA; Center for Computational Biology, University of California, Berkeley, CA 94720, USA.
⁶ QB3 Functional Genomics Laboratory, University of California, Berkeley, CA 94720, USA.
⁷ Department of Statistics, University of California, Berkeley, CA 94720, USA; Center for Computational Biology, University of California, Berkeley, CA 94720, USA.
⁸ Division of Biostatistics, University of California, Berkeley, CA 94720, USA; Department of Statistics, University of California, Berkeley, CA 94720, USA; Center for Computational Biology, University of California, Berkeley, CA 94720, USA.
⁹ Division of Biostatistics, University of California, Berkeley, CA 94720, USA.
¹⁰ Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA; Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720, USA; QB3 Functional Genomics Laboratory, University of California, Berkeley, CA 94720, USA. Electronic address: jngai@berkeley.edu.

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.

Keywords: HBC; Wnt; branching lineage; horizontal basal cell; lineage trajectory; olfactory epithelium; scRNA-seq; stem cells.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Adult Stem Cells* / cytology
Adult Stem Cells* / metabolism
Animals
Cell Division / physiology*
Mice
Mice, Transgenic
Multipotent Stem Cells* / cytology
Multipotent Stem Cells* / metabolism
Olfactory Mucosa* / cytology
Olfactory Mucosa* / metabolism
Wnt Signaling Pathway / physiology*

Abstract

Publication types

MeSH terms

Grants and funding