A Single-Cell Atlas of the Human Healthy Airways Deprez, Marie; Zaragosi, Laure-Emmanuelle; Truchi, Marin ...
American journal of respiratory and critical care medicine,
12/2020, Letnik:
202, Številka:
12
Journal Article
Recenzirano
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The respiratory tract constitutes an elaborate line of defense that is based on a unique cellular ecosystem.
We aimed to investigate cell population distributions and transcriptional changes along ...the airways by using single-cell RNA profiling.
We have explored the cellular heterogeneity of the human airway epithelium in 10 healthy living volunteers by single-cell RNA profiling. A total of 77,969 cells were collected at 35 distinct locations, from the nose to the 12th division of the airway tree.
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 distinct cellular proportions in different regions of the airways. It reveals differential gene expression between identical cell types (suprabasal, secretory, and multiciliated cells) from the nose (
,
,
) and tracheobronchial (
,
) airways. By contrast, cell-type-specific gene expression is stable across all tracheobronchial samples. Our atlas improves the description of ionocytes, pulmonary neuroendocrine cells, and brush cells and identifies a related population of
-positive cells. We also report the association of
with dividing cells that are reminiscent of previously described mouse "hillock" cells and with squamous cells expressing
and
.
Robust characterization of a single-cell cohort in healthy airways establishes a valuable resource for future investigations. The precise description of the continuum existing from the nasal epithelium to successive divisions of the 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.
Extensive outcrops of serpentinized peridotite in melt‐starved spreading corridors of the ultraslow easternmost Southwest Indian Ridge are hypothesized to be due to slip on successive long‐offset ...normal faults that alternate polarity (flip‐flop detachment faults). We investigate the nature of the oceanic crust which forms under these conditions, using seismic reflection data acquired during the SISMOSMOOTH 2014 cruise. Using 3‐D binning, the seismic profiles were binned elastically, while three of the profiles shot closely were merged into one to take advantage of the larger air gun source volume. Using a poststack imaging sequence, we observe several types of reflectors at crustal and infracrustal depths, in the axial valley and off‐axis. Correlating our seismic observations with Residual Mantle Bouguer gravity anomalies and seafloor observations, we find that our results are explicable in the framework of the flip‐flop hypothesis of detachment faulting. Reflectors imaged down to 5 km into the basement and interpreted as due to damaged zones outlining the detachment faults dip 50° at the early stages, while at late stages after developing offsets >10 km, they dip 25°. Other reflectors observed in the crust are interpreted as moderate offset (<200 m) normal faults accommodating deformation and alteration in the hanging wall and channeling the sparse melt to the seafloor. We interpret these and other observed seismic reflectors in the frame of a two‐phase evolutionary sequence over the lifetime of two successive flip‐flop detachment faults: exhumation, footwall flexure, damage, serpentinization, and incipient magmatism in the footwall of one detachment fault; followed by further tectonic damage, alteration, and incipient magmatism in the hanging wall of the next detachment fault.
Key Points
Seismic reflectivity structure of amagmatic spreading corridor reveals signatures of possible flip‐flop detachment faults
Detachment faults are steep‐dipping (>45°) in the upper 5 km of the ultramafic basement at the early stages and more shallow dipping (25°) after developing offsets >10 km
Seismic reflectivity structure consistent with two‐phase accretion history: (1) tectonic exhumation in the footwall of a detachment fault, and (2) further faulting, alteration, and magmatic infiltration in the hanging wall of the next detachment fault
Breaking the lithosphere in extension without exceeding the driving far-field forces available on Earth is a tough quantitative modeling problem. One can tear it apart by propagation of an existing ...oceanic basin or weakness zone or one must assist rifting with magmatic processes, which drop the effective stress and weakens locally the lithosphere. While previous 3D models have demonstrated that non-cylindrical plumes produce almost cylindrical rift structures in a lithosphere under slight far-field loading, our contribution goes one step further by producing models of complete continental break-up. We investigate in details how the rheological stratification of the continental lithosphere interacting with active mantle plume influences the geometry and dynamics of rifting to continental break-up in 3D. We find that, irrespective of the rheological stratification, a plume-induced rifting process always occurs in two stages: an early crustal rifting stage and a late lithospheric necking (breakup) stage. In case of a rheologically decoupled lithosphere, initial brittle deformation is concentrated in the upper crust and strongly localized due to compensating ductile flow of lower-crustal material (core complex extension mode). On the contrary, rheological coupling between upper crust and lithospheric mantle results in highly distributed brittle deformation in the crust above mantle plume head (wide rift mode). Both core complex-like and wide rifting are followed by an abrupt transition to narrow rift stage when a localized ascent of mantle plume material focuses high strain along faults zones breaking through the entire lithosphere. The Main Ethiopian Rift, the Basin and Range province, and the East Shetland Basin may be natural examples of regions that have passed through these two stages of extension. Across-strike and along-strike asymmetry of break-up patterns arising spontaneously within initially symmetrical and laterally homogenous environment seems to be an intrinsic characteristic of plume-induced rifting.
Display omitted
•Rheological coupling favors wide rift mode of initial extension.•Mechanically decoupled lithosphere is extended according to core complex mode.•Localized uplift of the mantle plume invokes a rapid transfer to the narrow rifting.•Asymmetry of break-up seems to be intrinsic characteristic of plume-induced rifting.
Given the polymicrobial nature of pulmonary infections in patients with cystic fibrosis (CF), it is essential to enhance our knowledge on the composition of the microbial community to improve patient ...management. In this study, we developed a pyrosequencing approach to extensively explore the diversity and dynamics of fungal and prokaryotic populations in CF lower airways.
Fungi and bacteria diversity in eight sputum samples collected from four adult CF patients was investigated using conventional microbiological culturing and high-throughput pyrosequencing approach targeting the ITS2 locus and the 16S rDNA gene. The unveiled microbial community structure was compared to the clinical profile of the CF patients. Pyrosequencing confirmed recently reported bacterial diversity and observed complex fungal communities, in which more than 60% of the species or genera were not detected by cultures. Strikingly, the diversity and species richness of fungal and bacterial communities was significantly lower in patients with decreased lung function and poor clinical status. Values of Chao1 richness estimator were statistically correlated with values of the Shwachman-Kulczycki score, body mass index, forced vital capacity, and forced expiratory volume in 1 s (p = 0.046, 0.047, 0.004, and 0.001, respectively for fungal Chao1 indices, and p = 0.010, 0.047, 0.002, and 0.0003, respectively for bacterial Chao1 values). Phylogenetic analysis showed high molecular diversities at the sub-species level for the main fungal and bacterial taxa identified in the present study. Anaerobes were isolated with Pseudomonas aeruginosa, which was more likely to be observed in association with Candida albicans than with Aspergillus fumigatus.
In light of the recent concept of CF lung microbiota, we viewed the microbial community as a unique pathogenic entity. We thus interpreted our results to highlight the potential interactions between microorganisms and the role of fungi in the context of improving survival in CF.
Airway transplantation could be an option for patients with proximal lung tumor or with end-stage tracheobronchial disease. New methods for airway transplantation remain highly controversial.
To ...establish the feasibility of airway bioengineering using a technique based on the implantation of stented aortic matrices.
Uncontrolled single-center cohort study including 20 patients with end-stage tracheal lesions or with proximal lung tumors requiring a pneumonectomy. The study was conducted in Paris, France, from October 2009 through February 2017; final follow-up for all patients occurred on November 2, 2017.
Radical resection of the lesions was performed using standard surgical techniques. After resection, airway reconstruction was performed using a human cryopreserved (-80°C) aortic allograft, which was not matched by the ABO and leukocyte antigen systems. To prevent airway collapse, a custom-made stent was inserted into the allograft. In patients with proximal lung tumors, the lung-sparing intervention of bronchial transplantation was used.
The primary outcome was 90-day mortality. The secondary outcome was 90-day morbidity.
Twenty patients were included in the study (mean age, 54.9 years; age range, 24-79 years; 13 men 65%). Thirteen patients underwent tracheal (n = 5), bronchial (n = 7), or carinal (n = 1) transplantation. Airway transplantation was not performed in 7 patients for the following reasons: medical contraindication (n = 1), unavoidable pneumonectomy (n = 1), exploratory thoracotomy only (n = 2), and a lobectomy or bilobectomy was possible (n = 3). Among the 20 patients initially included, the overall 90-day mortality rate was 5% (1 patient underwent a carinal transplantation and died). No mortality at 90 days was observed among patients who underwent tracheal or bronchial reconstruction. Among the 13 patients who underwent airway transplantation, major 90-day morbidity events occurred in 4 (30.8%) and included laryngeal edema, acute lung edema, acute respiratory distress syndrome, and atrial fibrillation. There was no adverse event directly related to the surgical technique. Stent removal was performed at a postoperative mean of 18.2 months. At a median follow-up of 3 years 11 months, 10 of the 13 patients (76.9%) were alive. Of these 10 patients, 8 (80%) breathed normally through newly formed airways after stent removal. Regeneration of epithelium and de novo generation of cartilage were observed within aortic matrices from recipient cells.
In this uncontrolled study, airway bioengineering using stented aortic matrices demonstrated feasibility for complex tracheal and bronchial reconstruction. Further research is needed to assess efficacy and safety.
clinicaltrials.gov Identifier: NCT01331863.
The East African Rift system （EARS） provides a unique system with the juxtaposition of two contrasting yet simultaneously formed rift branches, the eastern, magma-rich, and the western, magma-poor, ...on either sides of the old thick Tanzanian craton embedded in a younger lithosphere. Data on the pre-rifr, syn-rift and post-rift far-field volcanic and tectonic activity show that the EARS formed in the context of the interaction between a deep mantle plume and a horizontally and vertically heterogeneous lithosphere under far-field tectonic extension. We bring quantitative insights into this evolution by implementing high-resolution 3D thermo-mechanical numerical deformation models of a lithosphere of realistic rheology. The models focus on the central part of the EARS. We explore scenarios of plumelithosphere interaction with plumes of various size and initial position rising beneath a tectonically pre-stretched lithosphere. We test the impact of the inherited rheological discontinuities （suture zones） along the craton borders, of the rheological structure, of lithosphere plate thickness variations, and of physical and mechanical contrasts between the craton and the embedding lithosphere. Our experiments indicate that the ascending plume material is deflected by the cratonic keel and preferentially channeled along one of its sides, leading to the formation of a large rift zone along the eastern side of the craton, with significant magmatic activity and substantial melt amount derived from the mantle plume material. We show that the observed asymmetry of the central EARS, with coeval amagmatic （western） and magmatic （eastern） branches, can be explained by the splitting of warm material rising from a broad plume head whose initial position is slightly shifted to the eastern side of the craton. In that case, neither a mechanical weakness of the contact between the craton and the embedding lithosphere nor the presence of second plume are required to produce simulations that match observations. This result reconciles the passive and active rift models and demonstrates the possibility of development of both magmatic and amagmatic rifts in identical geotectonic environments.
Tracheobronchial injury is a heterogeneous entity comprising multiple rare and potentially life-threatening scenarios. We performed a systematic literature review focusing on post-intubation tracheal ...injuries (PiTIs) and post-traumatic tracheobronchial injuries (PTTBIs).PiTIs are often longitudinal lacerations of the middle third of the membranous trachea. Subcutaneous emphysema of the face and trunk following tracheal intubation should immediately trigger the diagnosis. Diagnosis may be suspected on the chest computed tomography (CT) and should be confirmed by bronchoscopic examination. Conservative management is encouraged for a spontaneously breathing or stable patient on noninvasive ventilation. Surgical repair is mandatory when mechanical ventilation is required and if bridging of the injury is impossible.PTTBIs are often associated with other severe injuries. Patients often present with massive subcutaneous emphysema and intractable pneumothorax. Diagnosis may be suspected on the chest CT and should be confirmed by bronchoscopic examination. Early surgical repair is indicated. In selected patients, conservative management can be considered.
During the evolution of continental rift systems, extension is thought to progressively focus in‐rift to the future breakup boundary while faults along the rift margins progressively deactivate. ...However, observational constraints on how strain is partitioned between rift axis and rift margins are still lacking. The Afar rift records the latest stages of rifting and incipient continental breakup. Here, we analyzed the recent MW 5.2 earthquake on the Western Afar Margin on March 24, 2018 and the associated seismic sequence of >500 earthquakes using 24 temporary seismic stations deployed during 2017–2018. We show seismicity occurring at lower crustal depths, from ∼15 to ∼30 km, with focal mechanisms and relocated earthquakes highlighting both west‐dipping and east‐dipping normal faults. We tested earthquake depth using InSAR by processing six independent interferograms using Sentinel‐1 data acquired from both ascending and descending tracks. None of them shows evidence of surface deformation. We tested possible ranges of depth by producing forward models for a fault located at progressively increasing depths. Models show that surface deformation is not significant for fault slip at depths greater than 15 km, in agreement with the hypocentral depth of 19 km derived from seismic data for the largest earthquake. Due to the localized nature of deep earthquakes near hot springs coupled with subsurface evidence for magmatism, we favor an interpretation of seismicity induced by migrating fluids such as magma or CO2. We suggest that deep fluid migration can occur at the rifted‐margin influencing seismicity during incipient continental rupture.
Plain Language Summary
The Earth's continents are thinned and broken by extensional forces along rift valleys. Rift valleys are bounded by big fractures (called border faults) that form at the inception of extension and that slip causing earthquakes. As thinning proceeds, molten rock (magma) can rise making its way through the crust. It is not well understood where and how the molten rocks migrate through the crust, and whether, e.g., the large border faults are exploited as pathways. The migration of magma, and the gasses and fluids it releases, can fracture rock causing earthquakes. In this study, we analyzed earthquakes occurring along border faults of the Afar rift of Ethiopia. We found that they occur deep in the crust where previous studies indicate the presence of magma. Our results could suggest that border faults could keep slipping and causing earthquakes as a result of the migration of magma into the deep parts of the crust.
Key Points
We studied fault activity and kinematics at the Western Afar Margin using seismicity and InSAR
We observed a seismic sequence occurring in the lower crust along both west‐dipping and east‐dipping faults
Deep seismicity could be caused by fluid migration in the lower crust
Imaging the lithosphere is key to understand mechanisms of extension as rifting progresses. Continental rifting results in a combination of mechanical stretching and thinning of the lithosphere, ...decompression upwelling, heating, sometimes partial melting of the asthenosphere, and potentially partial melting of the mantle lithosphere. The northern East African Rift system is an ideal locale to study these processes as it exposes the transition from tectonically active continental rifting to incipient seafloor spreading. Here we use S‐to‐P receiver functions to image the lithospheric structure beneath the northernmost East African Rift system where it forms a triple junction between the Main Ethiopian rift, the Red Sea rift, and the Gulf of Aden rift. We image the Moho at 31 ± 6 km beneath the Ethiopian plateau. The crust is 28 ± 3 km thick beneath the Main Ethiopian rift and thins to 23 ± 2 km in northern Afar. We identify a negative phase, a velocity decrease with depth, at 67 ± 3 km depth beneath the Ethiopian plateau, likely associated with the lithosphere‐asthenosphere boundary (LAB), and a lack of a LAB phase beneath the rift. Using observations and waveform modeling, we show that the LAB phase beneath the plateau is likely defined by a small amount of partial melt. The lack of a LAB phase beneath the rift suggests melt percolation through the base of the lithosphere beneath the northernmost East African Rift system.
Key Points
S‐to‐P receiver functions image lithospheric discontinuities beneath northern East African Rift
The Moho shallows from 28 km in the MER along the rift to 23 km in the northern Afar triple junction
The LAB is strong beneath the Ethiopian plateau but not imaged beneath the rift valley in Afar or MER
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