Injury Activates Transient Olfactory Stem Cell States with Diverse Lineage Capacities

Abstract

Summary 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.

Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia

“…The presence of Ace2 and Tmprss2 transcripts in mouse WOM and their absence in purified OSNs suggest that the molecular components that enable CoV-2 entry into cells are largely expressed in non-neuronal cell types in the mouse nasal epithelium. To identify the specific cell types that express Ace2 and Tmprss2, we examined two recently published mouse OE scSeq datasets 49,50 . This analysis confirmed our results from bulk RNA-seq, as mature OSNs from either dataset did not express Ace2 (zero cells express Ace2 out of 5337 and 51 OSNs, respectively, Figures 2C, 2D).…”

“…Single-cell RNA-seq data from HBC-derived cells from Fletcher et al and Gadye et al 37,49 , labeled via Krt5-CreER driver mice, were downloaded from GEO at accession GSE99251 using the file "GSE95601_oeHBCdiff_Cufflinks_eSet_counts_table.txt.gz". Processing was performed as described above, including total counts normalization and filtering for highly variable genes using the SPRING gene filtering function "filter_genes" with parameters (75,20,10).…”

“…It therefore remains unclear whether any cell types in the OE express ACE2, TMPRSS2 or other molecules involved in coronavirus entry, which would render them susceptible to direct infection by CoV-2. To address the hypothesis that CoV-2 causes anosmia through primary effects on the OE, we queried publicly available mouse, nonhuman primate and human RNA sequencing (RNASeq) and scSeq datasets that include definitive OE populations to assess CoV-2-related gene expression 37,46,[48][49][50][51][52][53][54][55] . We also mapped scSeq data across different datasets to compare observed gene expression levels from nasal samples to samples obtained from other airway tissues.…”

Hepatocyte growth factor plays a dual role in tendon‐derived stem cell proliferation, migration, and differentiation

“…of tendon function (Bi et al, 2007). However, similar to other stem cells (Gadye et al, 2017;Lin et al, 2017), the detailed mechanisms underlying the self-renewal and differentiation potential of TDSCs are not fully understood (Lui & Chan, 2011;Zhou et al, 2010).…”

Performance Assessment and Selection of Normalization Procedures for Single-Cell RNA-seq

“…We wish to emphasize that although scone has demonstrated its usefulness in published studies (e.g., Fletcher et al [38], Afik et al [39], Gadye et al [40], and Martin-Gayo et al [41]) and normalization can help remove unwanted variation from the data, a careful experimental design is the most important aspect of a successful use of scRNA-seq. In fact, if the biological effects of interest are completely confounded with unwanted technical effects, no statistical method will be able to extract meaningful signal from the data [5].…”