Transcription factor TAp73 and microRNA-449 complement each other to support multiciliogenesis

Wildung, Merit; Esser, Tilman Uli; Grausam, Katie B.; Wiedwald, Cornelia; Volceanov-Hahn, Larisa; Riedel, Dietmar; Beuermann, Sabine; Li, Li; Zylla, Jessica Lynn Simcox; Guenther, Ann Kathrin; Wienken, Magdalena; Ercetin, Evrim; Han, Zhiyuan; Bremmer, Felix; Shomroni, Orr; Andreas, Stefan; Zhao, Haotian; Lizé, Muriel

doi:10.1038/s41418-019-0332-7

Cited by 25 publications

(24 citation statements)

References 76 publications

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“…More than half of the highly active TF regulons identified in our dataset (shared and subtype-specific) had also been described in a previous study ( Mack et al., 2018 ). In addition, SCENIC suggested additional TF regulons within the PF-Ependymal-like metaprogram, including RFX2 and TP73 , both of which are implicated in ciliogenesis ( Figure 2 E) ( Nemajerova et al., 2016 ; Wildung et al., 2019 ; Chung et al., 2014 ). TF signatures of PF-NSC-like cells included JUN , FOS , and ATF3 , all of which are also top signature genes of this subpopulation ( Figure 2 E).…”

Section: Resultsmentioning

confidence: 99%

Single-Cell RNA-Seq Reveals Cellular Hierarchies and Impaired Developmental Trajectories in Pediatric Ependymoma

et al. 2020

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Summary Ependymoma is a heterogeneous entity of central nervous system tumors with well-established molecular groups. Here, we apply single-cell RNA sequencing to analyze ependymomas across molecular groups and anatomic locations to investigate their intratumoral heterogeneity and developmental origins. Ependymomas are composed of a cellular hierarchy initiating from undifferentiated populations, which undergo impaired differentiation toward three lineages of neuronal-glial fate specification. While prognostically favorable groups of ependymoma predominantly harbor differentiated cells, aggressive groups are enriched for undifferentiated cell populations. The delineated transcriptomic signatures correlate with patient survival and define molecular dependencies for targeted treatment approaches. Taken together, our analyses reveal a developmental hierarchy underlying ependymomas relevant to biological and clinical behavior.

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Section: Resultsmentioning

confidence: 99%

Single-Cell RNA-Seq Reveals Cellular Hierarchies and Impaired Developmental Trajectories in Pediatric Ependymoma

et al. 2020

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“…FOXJ1, CBE1, GemC1, TAp73, and TAp79 are key drivers of multimotile ciliogenesis in differentiating AECs by upregulating the expression of downstream genes involved in cilia assembly, motility, and structure ( 6 , 62 , 76 , 81 , 144 , 214 ). In vivo studies of knockout mice showed a pronounced loss of cilia and an absence of airway MCC ( 6 , 28 , 144 , 202 ). Interestingly, infection by common respiratory viruses such as respiratory syncytial virus (RSV), rhinovirus, and influenza can downregulate the expression of critical genes involved in development of motile cilia, although the pathophysiology remains undefined ( 40 , 117 , 145a ).…”

Section: Respiratory Cilia: Structure Function and Expressionmentioning

confidence: 99%

First contact: the role of respiratory cilia in host-pathogen interactions in the airways

Kuek

Lee

2020

American Journal of Physiology-Lung Cellular and Molecular Phys

128

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Respiratory cilia are the driving force of the mucociliary escalator, working in conjunction with secreted airway mucus to clear inhaled debris and pathogens from the conducting airways. Respiratory cilia are also one of the first contact points between host and inhaled pathogens. Impaired ciliary function is a common pathological feature in patients with chronic airway diseases, increasing susceptibility to respiratory infections. Common respiratory pathogens including viruses, bacteria and fungi have been shown to target cilia and/or ciliated airway epithelial cells, resulting in a disruption of mucociliary clearance that may facilitate host infection. Despite being an integral component of airway innate immunity, the role of respiratory cilia and their clinical significance during airway infections is still poorly understood. This review examines the expression, structure, and function of respiratory cilia during pathogenic infection of the airways. This review also discusses specific known points of interaction of bacteria, fungi, and viruses with respiratory cilia function. The emerging biological functions of motile cilia relating to intracellular signaling and their potential immuno-regulatory roles during infection will also be discussed.

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“…Previous studies indicated that the distal end of the FT had a higher proliferation rate and self-renewal ability, with basal stem cells enriched in this region [ 8 ]. p73 is expressed in progenitor and ciliated cells and was shown to be necessary for ciliogenesis [ 28 , 29 , 30 ]. To identify the progenitor basal stem cells in the epithelial sheet, we stained the FT with anti-Ki67 and p73 antibodies.…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies reported that p73 was co-expressed with Foxj1 in basal cells of mice trachea, and was necessary for ependymal cell maturation, suggesting that p73 is needed for MCCs differentiation [ 28 , 36 ]. In p73 knockout mice, the FT showed defective ciliogenesis [ 28 , 30 , 37 ]. Thus, p73 and Ki67 have been shown to provide useful markers for identifying basal stem cells in FT.…”

Section: Discussionmentioning

confidence: 99%

Fallopian Tube Basal Stem Cells Reproducing the Epithelial Sheets In Vitro—Stem Cell of Fallopian Epithelium

2020

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The fallopian tube (FT) is an important reproductive organ in females. The luminal epithelium of the FT is composed of highly polarized secretory and ciliated cells. Recently, accumulating lines of evidence have suggested that the origin of high-grade serous ovarian carcinoma (HGSC) is fallopian tube epithelial cells (FTECs). Due to the lack of a high-fidelity model for FTECs in vitro, homeostasis, differentiation, as well as the transformation of FTECs are still enigmatic. In this study, we optimized the culture condition for the stable expansion of basal stem cells, as well as inducing differentiation of basal cells into polarized secretory and ciliated cells in the air–liquid interface (ALI) condition suitable for long-term culture. This storable culture method of FTECs provides a versatile platform for studying differentiation mechanisms, intercellular communication, and transformation to HGSC, as well as the physiological function of the FT in vitro.

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Transcription factor TAp73 and microRNA-449 complement each other to support multiciliogenesis

Cited by 25 publications

References 76 publications

Single-Cell RNA-Seq Reveals Cellular Hierarchies and Impaired Developmental Trajectories in Pediatric Ependymoma

Single-Cell RNA-Seq Reveals Cellular Hierarchies and Impaired Developmental Trajectories in Pediatric Ependymoma

First contact: the role of respiratory cilia in host-pathogen interactions in the airways

Fallopian Tube Basal Stem Cells Reproducing the Epithelial Sheets In Vitro—Stem Cell of Fallopian Epithelium

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