Injury Activates Transient Olfactory Stem Cell States With Diverse Lineage Capacities

Cell Stem Cell, 2017

Recommended citation: Levi Gadye*, Diya Das*, Michael A. Sanchez*, Kelly Street, Davide Risso, Ariane Baudhuin, Michael B. Cole, Allon Wagner, Yoon Gi Choi, Elizabeth Purdom, Sandrine Dudoit, Nir Yosef, John Ngai and Russell B. Fletcher. (2017). Injury Activates Transient Olfactory Stem Cell States With Diverse Lineage Capacities. Cell Stem Cell 21, 775-790.e9. https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(17)30452-6

Abstract

Tissue homeostasis and regeneration are mediated by programs of adult stem cell renewal and differentiation. However, the mechanisms that regulate stem cell fates under such widely varying conditions are not fully understood. Using single-cell techniques, we assessed the transcriptional changes associated with stem cell self-renewal and differentiation and followed the maturation of stem cell-derived clones using sparse lineage tracing in the regenerating mouse olfactory epithelium. Following injury, quiescent olfactory stem cells rapidly shift to activated, transient states unique to regeneration and tailored to meet the demands of injury-induced repair, including barrier formation and proliferation. Multiple cell fates, including renewed stem cells and committed differentiating progenitors, are specified during this early window of activation. We further show that Sox2 is essential for cells to transition from the activated to neuronal progenitor states. Our study highlights strategies for stem cell-mediated regeneration that may be conserved in other adult stem cell niches.

Data and Code

The GEO accession numbers for the RNA-sequencing data reported in this paper are GSE95601 and GSE99251.

The code can be found at https://github.com/diyadas/HBC-regen.

Interview

My co-author, Levi Gadye, describes this paper in an interview with his former graduate program.