Notch1 maintains dormancy of olfactory horizontal basal cells, a reserve neural stem cell

Herrick, Daniel B.; Lin, Brian M.; Peterson, Julia; Schnittke, Nikolai; Schwob, James E.

doi:10.1073/pnas.1701333114

Cited by 67 publications

(93 citation statements)

References 81 publications

(85 reference statements)

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“…An interesting observation from the cellular trajectory of gene Trp63 shows that the expression levels of cells in S 10 (HBC1) change from high to low and they become rather low before the cells transit into other cellular states, which was also observed in the previous study (Schnittke et al, 2015) ( Figure 6D). The pathway enrichment analysis indicates that p53 signaling pathway plays an important role during the cellular transition from HBCs to GBCs, which is consistent with the previous observations (Herrick et al, 2017) (Figure 6E). It also shows that the pseudotime ordering of cells generated by SOMSC is consistent with previous study (Schnittke et al, 2015).…”

Section: Somsc On Scrna-seq Data Of Mouse Haematopoietic Stem Cell DIsupporting

confidence: 92%

SOMSC: Self-Organization-Map for High-Dimensional Single-Cell Data of Cellular States and Their Transitions

Peng

Nie

2017

Preprint

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Measurement of gene expression levels for multiple genes in single cells provides a powerful approach to study heterogeneity of cell populations and cellular plasticity. While the expression levels of multiple genes in each cell are available in such data, the potential connections among the cells (e.g. the cellular state transition relationship) are not directly evident from the measurement. Classifying the cellular states, identifying their transitions among those states, and extracting the pseudotime ordering of cells are challenging due to the noise in the data and the high-dimensionality in the number of genes in the data. In this paper we adapt the classical self-organizing-map (SOM) approach for single-cell gene expression data (SOMSC), such as those based on single cell qPCR and single cell RNA-seq. In SOMSC, a cellular state map (CSM) is derived and employed to identify cellular states inherited in the population of the measured single cells. Cells located in the same basin of the CSM are considered as in one cellular state while barriers among the basins in CSM provide information on transitions among the cellular states. A cellular state transitions path (e.g. differentiation) and a temporal ordering of the measured single cells are consequently obtained. In addition, SOMSC could estimate the cellular state replication probability and transition probabilities. Applied to a set of synthetic data, one single-cell qPCR data set on mouse early embryonic development and two single-cell RNA-seq data sets, SOMSC shows effectiveness in capturing cellular states and their transitions presented in the high-dimensional single-cell data. This approach will have broader applications to analyzing cellular fate specification and cell

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Section: Somsc On Scrna-seq Data Of Mouse Haematopoietic Stem Cell DIsupporting

confidence: 92%

SOMSC: Self-Organization-Map for High-Dimensional Single-Cell Data of Cellular States and Their Transitions

Peng

Nie

2017

Preprint

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“…Notably, injury models involving the direct loss of SUSs have been shown to activate the HBCs which in turn proliferate and replenish the lost cells, thereby reconstituting the olfactory epithelium homeostasis [ 68 ]. Mechanistically, loss of Notch signaling pathways between SUSs and HBCs leads to the breakdown of mitotic dormancy of HBCs by downregulating tumor protein p63 [ 69 ]. In light of these critical functional roles, we speculate that the apparent loss of smell could be a result of viral load in SUSs, BGCs and OSCs.…”

Section: Discussion and Future Directionsmentioning

confidence: 99%

The Cellular basis of loss of smell in 2019-nCoV-infected individuals

Gupta

Mohanty

Mittal

et al. 2020

Briefings in Bioinformatics

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A prominent clinical symptom of 2019-novel coronavirus (nCoV) infection is hyposmia/anosmia (decrease or loss of sense of smell), along with general symptoms such as fatigue, shortness of breath, fever and cough. The identity of the cell lineages that underpin the infection-associated loss of olfaction could be critical for the clinical management of 2019-nCoV-infected individuals. Recent research has confirmed the role of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) as key host-specific cellular moieties responsible for the cellular entry of the virus. Accordingly, the ongoing medical examinations and the autopsy reports of the deceased individuals indicate that organs/tissues with high expression levels of ACE2, TMPRSS2 and other putative viral entry-associated genes are most vulnerable to the infection. We studied if anosmia in 2019-nCoV-infected individuals can be explained by the expression patterns associated with these host-specific moieties across the known olfactory epithelial cell types, identified from a recently published single-cell expression study. Our findings underscore selective expression of these viral entry-associated genes in a subset of sustentacular cells (SUSs), Bowman’s gland cells (BGCs) and stem cells of the olfactory epithelium. Co-expression analysis of ACE2 and TMPRSS2 and protein–protein interaction among the host and viral proteins elected regulatory cytoskeleton protein-enriched SUSs as the most vulnerable cell type of the olfactory epithelium. Furthermore, expression, structural and docking analyses of ACE2 revealed the potential risk of olfactory dysfunction in four additional mammalian species, revealing an evolutionarily conserved infection susceptibility. In summary, our findings provide a plausible cellular basis for the loss of smell in 2019-nCoV-infected patients.

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“…Loss of the Notch1 receptor in HBCs under homeostatic conditions induces their differentiation. Following ablation of sustentacular cells in the olfactory epithelium, Notch signaling in HBCs is found to be downregulated, coinciding with their proliferation (Herrick et al, ). Notch ligands from the airway basal cells are required for maintenance of their daughter secretory progenitors; without Notch signaling, secretory progenitors undergo terminal differentiation into ciliated cells (Pardo‐Saganta et al, ).…”

Section: Conserved Signaling Pathways Maintain Tissue Homeostasismentioning

confidence: 99%

“…Notch plays dual roles in the olfactory epithelium, where it inhibits differentiation of stem cells during homeostatic maintenance and also promotes sustentacular (support) cell fates after injury (Herrick, Guo, Jang, Schnittke, & Schwob, 2018;Herrick, Lin, Peterson, Schnittke, & Schwob, 2017). Loss of the Notch1 receptor in HBCs under homeostatic conditions induces their differentiation.…”

Section: Self-renewal and Differentiationmentioning

confidence: 99%

Cellular mechanisms of epithelial stem cell self‐renewal and differentiation during homeostasis and repair

Das

Fletcher

Ngai

2019

WIREs Developmental Biology

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Epithelia in adult mammals exhibit remarkable regenerative capacities owing to the presence of adult stem cells, which self‐renew and differentiate to replace cells lost to normal turnover or injury. The mechanisms supporting tissue homeostasis and injury‐induced repair often differ from each other as well as from those used in embryonic development. Recent studies have also highlighted the phenomenon of cellular plasticity in adult tissues, in which differentiated cells can change fate and even give rise to new stem cell populations to complement the canonical stem cells in promoting repair following injury. Signaling pathways such as WNT, bone morphogenetic protein, and Sonic Hedgehog play critical roles in stem cell maintenance and cell fate decisions across diverse epithelia and conditions, suggesting that conserved mechanisms underlie the regenerative capacity of adult epithelial structures. This article is categorized under: Gene Expression and Transcriptional Hierarchies > Regulatory Mechanisms Adult Stem Cells, Tissue Renewal, and Regeneration > Tissue Stem Cells and Niches Adult Stem Cells, Tissue Renewal, and Regeneration > Stem Cell Differentiation and Reversion Adult Stem Cells, Tissue Renewal, and Regeneration > Regeneration

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Notch1 maintains dormancy of olfactory horizontal basal cells, a reserve neural stem cell

Cited by 67 publications

References 81 publications

SOMSC: Self-Organization-Map for High-Dimensional Single-Cell Data of Cellular States and Their Transitions

SOMSC: Self-Organization-Map for High-Dimensional Single-Cell Data of Cellular States and Their Transitions

The Cellular basis of loss of smell in 2019-nCoV-infected individuals

Cellular mechanisms of epithelial stem cell self‐renewal and differentiation during homeostasis and repair

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