Exploration of the Cell-Cycle Genes Found Within the RIKEN FANTOM2 Data Set

Forrest, Alan

doi:10.1101/gr.1012403

Cited by 14 publications

(12 citation statements)

References 40 publications

(32 reference statements)

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“…Analyses of cell cycle regulation genes in these two cell types may identify differences between mammalian and lower vertebrate SCs and illuminate a road map for targeted manipulation of genes to induce SC conversion to HCs in mammals. It is estimated that the mammalian cells may have up to 1,000 genes that are involved in cell cycle regulation (Forrest et al, 2003 ). We examined the expression of 223 genes commonly assayed in a PCR array for cell cycle regulation.…”

Section: Resultsmentioning

confidence: 99%

Cell-Specific Transcriptome Analysis Shows That Adult Pillar and Deiters' Cells Express Genes Encoding Machinery for Specializations of Cochlear Hair Cells

Liu

Chen

Giffen

et al. 2018

Front. Mol. Neurosci.

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The mammalian auditory sensory epithelium, the organ of Corti, is composed of hair cells and supporting cells. Hair cells contain specializations in the apical, basolateral and synaptic membranes. These specializations mediate mechanotransduction, electrical and mechanical activities and synaptic transmission. Supporting cells maintain homeostasis of the ionic and chemical environment of the cochlea and contribute to the stiffness of the cochlear partition. While spontaneous proliferation and transdifferentiation of supporting cells are the source of the regenerative response to replace lost hair cells in lower vertebrates, supporting cells in adult mammals no longer retain that capability. An important first step to revealing the basic biological properties of supporting cells is to characterize their cell-type specific transcriptomes. Using RNA-seq, we examined the transcriptomes of 1,000 pillar and 1,000 Deiters' cells, as well as the two types of hair cells, individually collected from adult CBA/J mouse cochleae using a suction pipette technique. Our goal was to determine whether pillar and Deiters' cells, the commonly targeted cells for hair cell replacement, express the genes known for encoding machinery for hair cell specializations in the apical, basolateral, and synaptic membranes. We showed that both pillar and Deiters' cells express these genes, with pillar cells being more similar to hair cells than Deiters' cells. The fact that adult pillar and Deiters' cells express the genes cognate to hair cell specializations provides a strong molecular basis for targeting these cells for mammalian hair cell replacement after hair cells are lost due to damage.

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Section: Resultsmentioning

confidence: 99%

Cell-Specific Transcriptome Analysis Shows That Adult Pillar and Deiters' Cells Express Genes Encoding Machinery for Specializations of Cochlear Hair Cells

Liu

Chen

Giffen

et al. 2018

Front. Mol. Neurosci.

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“…To identify the possible genes regulating the cell cycling of Lgr5+ progenitors, we took advantage of microarray analysis to compare the expression of genes regulating the cell cycle and cell proliferation in ALPs and BLPs. It is reported that over 1,000 cell cycle genes might exist in the mammalian cell [29]. We examined the expression of 60 genes known to be involved in the cell cycle and that are commonly assayed in cell cycle PCR arrays.…”

Section: Resultsmentioning

confidence: 99%

Characterization of Lgr5+ progenitor cell transcriptomes in the apical and basal turns of the mouse cochlea

et al. 2016

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Lgr5+ supporting cells (SCs) are enriched hair cell (HC) progenitors in the cochlea, and several studies have shown a difference in the proliferation and HC regeneration ability of SCs between the apical and basal turns. However, the detailed differences between the transcriptomes of the apical and basal Lgr5+ SCs have not yet been investigated. We found that when isolated by FACS, Lgr5+ cells from the apex generated significantly more HCs and had significantly higher proliferation and mitotic HC regeneration ability compared to those from the base. Next, we used microarray analysis to determine the transcriptome expression profiles of Lgr5+ progenitors from the apex and the base. We first analyzed the genes that were enriched and differentially expressed in Lgr5+ progenitors from the apex and the base. Then we analyzed the cell cycle genes and the transcription factors that might regulate the proliferation and differentiation of Lgr5+ progenitors. Lastly, to further analyze the role of differentially expressed genes and to gain an overall view of the gene network in cochlear HC regeneration, we created a protein-protein interaction network. Our datasets suggest the possible genes that might regulate the proliferation and HC regeneration ability of Lgr5+ progenitors, and these genes might provide new therapeutic targets for HC regeneration in the future.

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“…The first mammalian NIMA-related kinases, Nek1, Nek2 and Nek3, were described by the Pawson and Nigg groups in the early 1990s [ 11 , 12 ]. However, sequencing of the human and mouse genomes unexpectedly revealed the presence of eleven genes that encode a distinct clade of mammalian serine/threonine kinases related to NIMA [ 13 ]. Hence, this family, termed Nek1 to Nek11, constitutes approximately 2% of the entire human kinome (Figure 1 ).…”

Section: Introductionmentioning

confidence: 99%

Mitotic regulation by NIMA-related kinases

2007

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The NIMA-related kinases represent a family of serine/threonine kinases implicated in cell cycle control. The founding member of this family, the NIMA kinase of Aspergillus nidulans, as well as the fission yeast homologue Fin1, contribute to multiple aspects of mitotic progression including the timing of mitotic entry, chromatin condensation, spindle organization and cytokinesis. Mammals contain a large family of eleven NIMA-related kinases, named Nek1 to Nek11. Of these, there is now substantial evidence that Nek2, Nek6, Nek7 and Nek9 also regulate mitotic events. At least three of these kinases, as well as NIMA and Fin1, have been localized to the microtubule organizing centre of their respective species, namely the centrosome or spindle pole body. Here, they have important functions in microtubule organization and mitotic spindle assembly. Other Nek kinases have been proposed to play microtubule-dependent roles in non-dividing cells, most notably in regulating the axonemal microtubules of cilia and flagella. In this review, we discuss the evidence that NIMA-related kinases make a significant contribution to the orchestration of mitotic progression and thereby protect cells from chromosome instability. Furthermore, we highlight their potential as novel chemotherapeutic targets.

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Exploration of the Cell-Cycle Genes Found Within the RIKEN FANTOM2 Data Set

Cited by 14 publications

References 40 publications

Cell-Specific Transcriptome Analysis Shows That Adult Pillar and Deiters' Cells Express Genes Encoding Machinery for Specializations of Cochlear Hair Cells

Cell-Specific Transcriptome Analysis Shows That Adult Pillar and Deiters' Cells Express Genes Encoding Machinery for Specializations of Cochlear Hair Cells

Characterization of Lgr5+ progenitor cell transcriptomes in the apical and basal turns of the mouse cochlea

Mitotic regulation by NIMA-related kinases

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