CDC20B is required for deuterosome-mediated centriole production in multiciliated cells

Revinski, Diego R.; Zaragosi, Laure-Emmanuelle; Boutin, Camille; Ruiz-Garcia, Sandra; Deprez, Marie; Rosnet, Olivier; Thomé, Virginie; Mercey, Olivier; Paquet, Agnès; Pons, Nicolas; Marcet, Brice; Kodjabachian, Laurent; Barbry, Pascal

doi:10.1101/218750

Cited by 28 publications

(51 citation statements)

References 57 publications

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“…Our study has also provided a first extensive gene signature of the deuterosomal population, which play a key role during differentiation of multicilated cells. In line with what has been shown recently by our group and others [32,35], cell-cycle related genes become re-expressed in this population on non-cycling cells. We have confirmed the very specific expression of CDC20B, a key player of centriole amplification [32], and have identified, both in human and mouse, a novel isoform of this transcript which displays higher expression than the annotated long isoform.…”

Section: Discussionsupporting

confidence: 90%

“…In line with what has been shown recently by our group and others [32,35], cell-cycle related genes become re-expressed in this population on non-cycling cells. We have confirmed the very specific expression of CDC20B, a key player of centriole amplification [32], and have identified, both in human and mouse, a novel isoform of this transcript which displays higher expression than the annotated long isoform. As the pre-mRNA corresponding to this short isoform comprises the miR-449-encoding intron, we suggest that this isoform should indeed be the major source of miR-449 in deuterosomal cells.…”

Section: Discussionsupporting

confidence: 90%

“…We confirmed the deuterosomal-specific expression of CDC20B, the miR-449 host gene. We have recently shown that CDC20B is a key regulator of centriole amplification by deuterosomes [32]. Incidentally, we noticed the existence of a novel and short isoform of this gene, arising from alternative splicing and results in the inclusion of a novel exon after the location of the miR-449 family ( Fig.…”

Section: Refining Cell Clustering Identifies 6 Additional Clusters Imentioning

confidence: 85%

“…Cells isolated with the C1 were visually inspected, and these experimental settings ensured the absence of cell doublets. We found that 4 cells out of 74 expressed GC specific genes (namely MUC5AC, MUC5B and TFF3), together with MCC specific genes (FOXJ1), and more specifically, immature MCC genes (PLK4, MYB and CDC20B) [32] (Supplemental Figure S5a, b). The result was further confirmed after reanalyzing a recent dataset published by others [29] (Supplemental Figure S5c).…”

Section: Goblet Cells Can Act As Differentiation Intermediates For Mumentioning

confidence: 92%

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Single-cell RNA sequencing reveals novel cell differentiation dynamics during human airway epithelium regeneration

García-Ruiz

Deprez

Lebrigand

et al. 2018

Preprint

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Background:It is usually considered that the upper airway epithelium is composed of multiciliated, goblet, secretory and basal cells, which collectively constitute an efficient first line of defense against inhalation of noxious substances. Upon injury, regeneration of this epithelium through proliferation and differentiation can restore a proper mucociliary function. However, in chronic airway diseases, the injured epithelium frequently displays defective repair leading to tissue remodeling, characterized by a loss of multiciliated cells and mucus hyper-secretion. Delineating drivers of differentiation dynamics and cell fate in the human airway epithelium is important to preserve homeostasis. Results:We have used single cell transcriptomics to characterize the sequence of cellular and molecular processes taking place during human airway epithelium regeneration. We have characterized airway subpopulations with high resolution and lineage inference algorithms have unraveled cell trajectories from basal to luminal cells, providing markers for specific cell populations, such as deuterosomal cells, i.e. precursors of multiciliated cells. We report that goblet cells, like secretory cells, can act as precursors of multiciliated cells. Our study provides a repertoire of molecules involved in key steps of the regeneration process, either keratins or components of the Notch, Wnt or BMP/TGFβ signaling pathways. Our findings were confirmed in independent experiments performed on fresh human and pig airway samples, and on mouse tracheal epithelial cells. Conclusions:Our single-cell RNA-seq study provides novel insights about airway epithelium differentiation dynamics, clarifies cell trajectories between secretory, goblet and multiciliated cells, identifies novel cell subpopulations, and maps the activation and repression of key signaling pathways.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 90%

Section: Refining Cell Clustering Identifies 6 Additional Clusters Imentioning

confidence: 85%

Section: Goblet Cells Can Act As Differentiation Intermediates For Mumentioning

confidence: 92%

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Single-cell RNA sequencing reveals novel cell differentiation dynamics during human airway epithelium regeneration

García-Ruiz

Deprez

Lebrigand

et al. 2018

Preprint

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“…populations could not be clustered separately and essentially differed by the level of expression of MUC5AC and MUC5B ( Figure E4) (12). We detected clusters of multiciliated cells (expressing high levels of FOXJ1, TPPP3, and SNTN) and deuterosomal cells, which correspond to precursors of multiciliated cells and express several specific markers: CCDC67/DEUP1, FOXN4 and CDC20B ( Figure 1C and 1D) (12,13). The suprabasal, secretory and multiciliated clusters each comprised a sub-cluster of cells that were only detected in nasal samples.…”

Section: Methodsmentioning

confidence: 91%

A single-cell atlas of the human healthy airways

Deprez

Zaragosi

Truchi

et al. 2019

Preprint

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184

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248 words) Rationale: The respiratory tract constitutes an elaborated line of defense based on a unique cellular ecosystem. Single-cell profiling methods enable the investigation of cell population distributions and transcriptional changes along the airways. Methods:We have explored cellular heterogeneity of the human airway epithelium in 10 healthy living volunteers by single-cell RNA profiling. 77,969 cells were collected by bronchoscopy at 35 distinct locations, from the nose to the 12 th division of the airway tree. Results:The resulting atlas is composed of a high percentage of epithelial cells (89.1%), but also immune (6.2%) and stromal (4.7%) cells with peculiar cellular proportions in different sites of the airways. It reveals differential gene expression between identical cell types (suprabasal, secretory, and multiciliated cells) from the nose (MUC4, PI3, SIX3) and tracheobronchial (SCGB1A1, TFF3) airways. By contrast, cell-type specific gene expression was stable across all tracheobronchial samples. Our atlas improves the description of ionocytes, pulmonary neuroendocrine (PNEC) and brush cells, which are likely derived from a common population of precursor cells. We also report a population of KRT13 positive cells with a high percentage of dividing cells which are reminiscent of "hillock" cells previously described in mouse. Conclusions:Robust characterization of this unprecedented large single-cell cohort establishes an important resource for future investigations. The precise description of the continuum existing from nasal epithelium to successive divisions of lung airways and the stable gene expression profile of these regions better defines conditions under which relevant tracheobronchial proxies of human respiratory diseases can be developed. Results Building a molecular cell atlas of the airways in healthy volunteers Data collectionCells were analyzed by droplet-based single-cell RNA sequencing (scRNA-seq), after isolation from 4 distinct locations using 2 sampling methods: (i) nasal biopsies (3 samples) and (ii) nasal brushings (4 samples), (iii) tracheal biopsies (carina, 1 st division, 9 samples), (iv) intermediate bronchial biopsies (5-6 th divisions, 10 samples), (v) distal brushings (9-12 th divisions, 9 samples) in 10 healthy volunteers ( Figure 1A, 1B, Figure E1A, Table E1). Optimized handling and dissociation protocols allowed the profiling of 77,969 single cells which were collected at 35 distinct positions of the airways, resulting in the detection of an average of 1,892 expressed genes per cell with 7,070 UMI per cell ( Figure E2A).Following batch correction and graph-based clustering, cell types were assigned to each cluster using well-established sets of marker genes ( Figure 1C, Figure E3). We identified 14 epithelial cell types, including 12 for the surface epithelium and 2 for submucosal glands, which collectively represented 89.1% of total cells ( Figure 1C-1E, Table E2; See also our interactive web tool https://www.genomique.eu/cellbrowser/HCA/?ds=HCA_airway_epithelium).Strom...

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5q11.2 deletion syndrome revisited—Further narrowing of the smallest region of overlap for the main clinical characteristics of the syndrome

Bayat

Broers

et al. 2021

American J of Med Genetics Pt A

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Microdeletions at 5q11.2 are rare. Subjects show a phenotypic spectrum that overlaps CHARGE syndrome and 22q11.2 deletion syndrome. A growing number of subjects present with learning difficulty and/or intellectual disability, immune deficiency, congenital heart malformation, and dysmorphism. DHX29 and IL6ST have been proposed as candidate genes for the development of the major clinical manifestations.We present a new case and narrow down the shortest region of overlap to evaluate possible candidate genes. Our case does not present developmental delay or immune deficiency indicating a reduced penetrance for some of the main clinical manifestations. The shortest region of overlap between subjects with deletions at 5q11.2 is approximately 450 kb (position 54.3-54.7 Mb). The narrowed region comprises 10 protein coding genes, including DHX29. DHX29 is a strong candidate gene for the main features of 5q11.2-microdeletion syndrome; however, our findings suggest a joined impact of several genes as the cause of the syndrome.

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CDC20B is required for deuterosome-mediated centriole production in multiciliated cells

Cited by 28 publications

References 57 publications

Single-cell RNA sequencing reveals novel cell differentiation dynamics during human airway epithelium regeneration

Single-cell RNA sequencing reveals novel cell differentiation dynamics during human airway epithelium regeneration

A single-cell atlas of the human healthy airways

5q11.2 deletion syndrome revisited—Further narrowing of the smallest region of overlap for the main clinical characteristics of the syndrome

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