Label‐retaining, quiescent globose basal cells are found in the olfactory epithelium

Jang, Wooseung; Chen, Xueyan; Flis, Daniel W.; Harris, Margaret; Schwob, James E.

doi:10.1002/cne.23530

Cited by 13 publications

(25 citation statements)

References 70 publications

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“…This antibody has been rigorously shown to stain immature OSNs (Schwob et al, ; Roskams, Cai, & Ronnett, ). The BioLegend antibody used in this study is the same Covance Tuj1 antibody used by our lab previously (Krolewski et al, ; Jang, Chen, Flis, Harris, & Schwob, ).…”

Section: Methodsmentioning

confidence: 99%

Dissecting LSD1‐Dependent Neuronal Maturation in the Olfactory Epithelium

Coleman

Lin

Schwob

2017

J of Comparative Neurology

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Neurons in the olfactory epithelium (OE) each express a single dominant olfactory receptor (OR) allele from among roughly 1,000 different OR genes. While monogenic and monoallelic OR expression has been appreciated for over two decades, regulators of this process are still being described; most recently, epigenetic modifiers have been of high interest as silent OR genes are decorated with transcriptionally repressive trimethylated histone 3 lysine 9 (H3K9me3) whereas active OR genes are decorated with transcriptionally activating trimethylated histone 3 lysine 4 (H3K4me3). The lysine specific demethylase 1 (LSD1) demethylates at both of these lysine residues and has been shown to disrupt neuronal maturation and OR expression in the developing embryonic OE. Despite the growing literature on LSD1 expression in the OE, a complete characterization of the timing of LSD1 expression relative to neuronal maturation and of the function of LSD1 in the adult OE have yet to be reported. To fill this gap, the present study determined that LSD1 (1) is expressed in early dividing cells before OR expression and neuronal maturation and decreases at the time of OR stabilization; (2) colocalizes with the repressor CoREST (also known as RCOR1) and histone deacetylase 2 in these early dividing cells; and (3) is required for neuronal maturation during a distinct time window between activating reserve stem cells (horizontal basal cells) and Neurogenin1 (+) immediate neuronal precursors. Thus, this study clarifies the role of LSD1 in olfactory neuronal maturation.

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Section: Methodsmentioning

confidence: 99%

Dissecting LSD1‐Dependent Neuronal Maturation in the Olfactory Epithelium

Coleman

Lin

Schwob

2017

J of Comparative Neurology

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“…Published data indicate that GBCs of the normal OE constitute a heterogeneous population, which includes relatively quiescent, long-lived stem cells (GBC Q ), dividing, Sox2/Pax6 + multipotent progenitors (GBC MPP ), rapidly dividing transit-amplifying cells (GBC TA ), and immediate neuronal progenitors (GBC INP ) (17,18,(31)(32)(33). The similarity of the composition of the HBC-derived clones at 4 d and 4 wk after recombination and p63 deletion suggests that the GBCs function similarly over that time period (Fig.…”

Section: An In Vivo Cfu Assay Identifies Activated Hbcs and Correlatementioning

confidence: 99%

Transcription factor p63 controls the reserve status but not the stemness of horizontal basal cells in the olfactory epithelium

Schnittke

Herrick

Lin

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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115

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Adult tissue stem cells can serve two broad functions: to participate actively in the maintenance and regeneration of a tissue or to wait in reserve and participate only when activated from a dormant state. The adult olfactory epithelium, a site for ongoing, life-long, robust neurogenesis, contains both of these functional stem cell types. Globose basal cells (GBCs) act as the active stem cell population and can give rise to all the differentiated cells found in the normal tissue. Horizontal basal cells (HBCs) act as reserve stem cells and remain dormant unless activated by tissue injury. Here we show that HBC activation following injury by the olfactotoxic gas methyl bromide is coincident with the down-regulation of protein 63 (p63) but anticipates HBC proliferation. Gain- and loss-of-function studies show that this down-regulation of p63 is necessary and sufficient for HBC activation. Moreover, activated HBCs give rise to GBCs that persist for months and continue to act as bona fide stem cells by participating in tissue maintenance and regeneration over the long term. Our analysis provides mechanistic insight into the dynamics between tissue stem cell subtypes and demonstrates that p63 regulates the reserve state but not the stem cell status of HBCs.

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“…Subsets of GBCs express differing levels of transcriptional regulators, likely reflecting lineage decisions or functional status as either a reserve stem cell, a transit amplifying cell, or an immediate neuronal precursor (Cau et al, 1997;Gokoffski et al, 2011;Jang et al, 2014). Our sorting technique, purifying OE c-KIT + cells for culture starting material, enriches for a GBC population.…”

Section: Phenotype Of Expansion-competent Gbc Cultures: Sustaining Thmentioning

confidence: 99%

Contribution of Polycomb group proteins to olfactory basal stem cell self-renewal in a novel c-KIT+ culture model and in vivo

et al. 2016

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Olfactory epithelium (OE) has a lifelong capacity for neurogenesis due to the presence of basal stem cells. Despite the ability to generate short-term cultures, the successful in vitro expansion of purified stem cells from adult OE has not been reported. We sought to establish expansion-competent OE stem cell cultures to facilitate further study of the mechanisms and cell populations important in OE renewal. Successful cultures were prepared using adult mouse basal cells selected for expression of c-KIT. We show that c-KIT signaling regulates self-renewal capacity and prevents neurodifferentiation in culture. Inhibition of TGFβ family signaling, a known negative regulator of embryonic basal cells, is also necessary for maintenance of the proliferative, undifferentiated state in vitro. Characterizing successful cultures, we identified expression of BMI1 and other Polycomb proteins not previously identified in olfactory basal cells but known to be essential for self-renewal in other stem cell populations. Inducible fate mapping demonstrates that BMI1 is expressed in vivo by multipotent OE progenitors, validating our culture model. These findings provide mechanistic insights into the renewal and potency of olfactory stem cells.

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Label‐retaining, quiescent globose basal cells are found in the olfactory epithelium

Cited by 13 publications

References 70 publications

Dissecting LSD1‐Dependent Neuronal Maturation in the Olfactory Epithelium

Dissecting LSD1‐Dependent Neuronal Maturation in the Olfactory Epithelium

Transcription factor p63 controls the reserve status but not the stemness of horizontal basal cells in the olfactory epithelium

Contribution of Polycomb group proteins to olfactory basal stem cell self-renewal in a novel c-KIT+ culture model and in vivo

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