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Stem Cells and Lung Regeneration

Kalpaj R. Parekh, Janna Nawroth, Albert Pai, Shana M. Busch, Christiana N. Senger, Amy L Ryan
2020 American Journal of Physiology - Cell Physiology  
Summary/Abstract The ability to replace defective cells in an airway with cells that can engraft, integrate and restore a functional epithelium could potentially cure a number of lung diseases.  ...  These advancements include novel lineage-traced animal models and single-cell RNA sequencing of human airway cells, which have provided critical information on the stem cell subtypes, transition states  ...  Ionocytes express higher levels of CFTR than any other large airway cell type in humans, and, in vitro, the relative abundance of human ionocytes indeed correlated with tissue-level CFTR function (133  ... 
doi:10.1152/ajpcell.00036.2020 pmid:32783658 fatcat:alqi6zts3bg5dibs24hq7zazva

Recent developments in mRNA-based Protein supplementation therapy to target Lung diseases

Itishri Sahu, AKM Ashiqul Haque, Brian Weidensee, Petra Weinmann, Michael SD. Kormann
2019 Molecular Therapy  
Many modifications have been made to produce high expressions of mRNA causing less immunogenicity and more stability.  ...  From the early ages of synthetic mRNA discovery, a great number of studies showed the versatile use of IVT mRNA as a novel approach to supplement faulty or absent protein and also as a vaccine.  ...  A revised airway epithelial hierarchy includes CFTR-expressing ionocytes. Nature 560, 319-324. 24. Castranova, V., Rabovsky, J., Tucker, J.H., and Miles, P.R. (1988).  ... 
doi:10.1016/j.ymthe.2019.02.019 pmid:30905577 pmcid:PMC6453549 fatcat:x4nqcakjcnh6bbh4lhktqrsdvy

Cigarette smoke triggers the expansion of a subpopulation of respiratory epithelial cells that express the SARS-CoV-2 receptor ACE2 [article]

Joan C Smith, Jason Meyer Sheltzer
2020 bioRxiv   pre-print
Using single-cell sequencing data, we demonstrate that ACE2 is expressed in a subset of epithelial cells that line the respiratory tract, including goblet cells, club cells, and alveolar type 2 cells.  ...  Chronic smoke exposure triggers a protective expansion of mucus-secreting goblet cells and a concomitant increase in ACE2 expression.  ...  A revised airway epithelial hierarchy includes CFTR-expressing ionocytes. Nature 560, 319-324 (2018). of the Surgeon General (US) & Office on Smoking and Health (US).  ... 
doi:10.1101/2020.03.28.013672 fatcat:cqmb5kbezfayzp3ogugqlsoedq

Can a Physiologic Insight "Resuscitate" Research in Cardiopulmonary Resuscitation?

Damon C. Scales, Brian P. Kavanagh
2019 American Journal of Respiratory and Critical Care Medicine  
A revised airway epithelial hierarchy includes CFTR-expressing ionocytes. Nature 2018;560:319-324. 11. Plasschaert LW, Žilionis R, Choo-Wing R, Savova V, Knehr J, Roma G, et al.  ...  Third, measuring the Airway Opening Index (or a version of it) should be easy, given that ETCO 2 monitors are now widely available, including in ambulances.  ... 
doi:10.1164/rccm.201810-1912ed pmid:30383400 pmcid:PMC6423109 fatcat:5aimerm36fg4bdebyq75azhosm

Chloride channels regulate differentiation and barrier functions of the mammalian airway

Mu He, Bing Wu, Wenlei Ye, Daniel D Le, Adriane W Sinclair, Valeria Padovano, Yuzhang Chen, Ke-Xin Li, Rene Sit, Michelle Tan, Michael J Caplan, Norma Neff (+3 others)
2020 eLife  
The conducting airway forms a protective mucosal barrier and is the primary target of airway disorders.  ...  by depleting epithelial progenitors.  ...  A revised airway epithelial hierarchy includes CFTR-544 expressing ionocytes.  ... 
doi:10.7554/elife.53085 fatcat:ap55us4lsrb4rdabibhol4uiwi

Single-cell analysis of human lung epithelia reveals concomitant expression of the SARS-CoV-2 receptor ACE2 with multiple virus receptors and scavengers in alveolar type II cells [article]

Guangchun Han, Ansam Sinjab, Warapen Treekitkarnmongkol, Patrick Brennan, Kieko Hara, Kyle Chang, Elena Bogatenkova, Beatriz Sanchez-Espiridion, Carmen Behrens, Boning Gao, Luc Girard, Jianjun Zhang (+20 others)
2020 bioRxiv   pre-print
We describe a population of ACE2-positive AT2 cells that co-express pathogen (including viral) receptors (e.g.  ...  Transcriptomic analysis revealed a diverse repertoire of airway lineages that included alveolar type I and II, bronchioalveolar, club/secretory, quiescent and proliferating basal, ciliated and malignant  ...  A revised airway epithelial hierarchy includes CFTR-expressing ionocytes. Nature 560, 319-324 (2018). 26. Laughney AM, et al.  ... 
doi:10.1101/2020.04.16.045617 fatcat:ror66bofirgknbtfbmxmcixnna

Cell-ID: gene signature extraction and cell identity recognition at individual cell level [article]

Akira Leo Cortal, Loredana Martignetti, Emmanuelle Six, Antonio Rausell
2020 bioRxiv   pre-print
We present here Cell-ID, a clustering-free multivariate statistical method for the robust extraction of per-cell gene signatures from single-cell RNA-seq.  ...  A single-cell atlas of the airway epithelium reveals the CFTR-rich pulmonary ionocyte, D. T. et al. A revised airway epithelial hierarchy includes CFTR-expressing ionocytes.  ...  A revised airway epithelial hierarchy includes CFTR-expressing ionocytes. Orit Rozenblatt-Rosen 4, The copyright holder for this preprint this version posted August 11, 2020.  ... 
doi:10.1101/2020.07.23.215525 fatcat:j4cv4ukll5aevbklqymfvo3a4a

3D cell culture models demonstrate a role for FGF and WNT signaling in regulation of lung epithelial cell fate and morphogenesis [article]

Anas Rabata, Radek Fedr, Karel Soucek, Ales Hampl, Zuzana Koledova
2020 bioRxiv   pre-print
We employed mouse 3D cell culture models and imaging to ex vivo study of a) the role of FGF ligands in lung epithelial morphogenesis and b) the interplay of FGF signaling with epithelial growth factor  ...  well as airway-like structures with club cells and ciliated cells.  ...  Evidence of an epithelial 575 stem/progenitor cell hierarchy in the adult mouse lung. Proc. Natl. Acad. Sci. 107, 1414-576 1419. doi:10.1073/pnas.0909207107. 577 Miller, L.-A. D., Wert, S.  ... 
doi:10.1101/2020.04.04.024943 fatcat:xgvxcklycnaxnjjdvpiq3jeb5u

The bitter end: T2R bitter receptor agonists elevate nuclear calcium and induce apoptosis in non-ciliated airway epithelial cells [article]

Derek B McMahon, Li Eon Kuek, Madeline E Johnson, Paige O Johnson, Rachel L.J. Horn, Ryan M Carey, Nithin D Adappa, James N Palmer, Robert J Lee
2021 bioRxiv   pre-print
Several airway diseases, including chronic rhinosinusitis, COPD, and cystic fibrosis, are characterized by epithelial remodeling, including loss of motile cilia and/or squamous metaplasia.  ...  This T2R-induced apoptosis may be a last-resort defense against infection, possibly when bacteria have breached the epithelial barrier and reach non-ciliated cells below.  ...  A revised airway epithelial hierarchy includes CFTR-expressing ionocytes. Nature 2018, 560(7718): 319-324. RR, Gerwin BI, Miyashita M, McMenamin M, Lechner JF, et al.  ... 
doi:10.1101/2021.05.16.444376 fatcat:tsftnjmoyvf3hcka7ujpxzdvoi

Progenitor identification and SARS-CoV-2 infection in human distal lung organoids

Ameen A. Salahudeen, Shannon S. Choi, Arjun Rustagi, Junjie Zhu, Vincent van Unen, Sean M. de la O, Ryan A. Flynn, Mar Margalef-Català, António J. M. Santos, Jihang Ju, Arpit Batish, Tatsuya Usui (+22 others)
2020 Nature  
model for human distal lung infections including COVID-19-associated pneumonia.  ...  We generated long-term feeder-free, chemically defined culture of distal lung progenitors as organoids derived from single adult human alveolar epithelial type II (AT2) or KRT5+ basal cells.  ...  A revised airway epithelial hierarchy includes CFTR-expressing ionocytes. Nature 560, 319-324 (2018). 36. Lukassen, S. et al.  ... 
doi:10.1038/s41586-020-3014-1 pmid:33238290 fatcat:lkjsd3sekzdube7n4ykdsrzcda

A Human Multi-Lineage Hepatic Organoid Model for Liver Fibrosis [article]

YUAN GUAN, Annik Enejder, Meiyue Wang, Zhuoqing Fang, Lu Cui, Shih-Yu Chen, Jingxiao Wang, Yalun Tan, Manhong Wu, Xinyu Chen, Patrik K. Johansson, Issra Osman (+4 others)
2020 bioRxiv   pre-print
Genome engineering and a hepatic organoid system was used to produce the first in vitro model for human liver fibrosis.  ...  The abnormal cholangiocytes promote the expansion of collagen-producing myofibroblasts with markedly increased PDGFRB; protein expression and an activated STAT3 signaling pathway.  ...  A revised airway epithelial hierarchy includes CFTR-expressing ionocytes. Nature 560, 319-324 (2018). 37. Plasschaert, L.W., et al.  ... 
doi:10.1101/2020.09.01.278473 fatcat:menicwwdqbc3diatsfztnumsyq

Identifying disease-critical cell types and cellular processes across the human body by integration of single-cell profiles and human genetics [article]

Karthik A. Jagadeesh, Kushal K Dey, Daniel T. Montoro, Steven Gazal, Jesse M Engreitz, Ramnik J Xavier, Alkes L. Price, Aviv Regev
2021 biorxiv/medrxiv  
Cellular dysfunction is a hallmark of disease.  ...  The inferred disease enrichments recapitulated known biology and highlighted novel relationships for different conditions, including GABAergic neurons in major depressive disorder (MDD), disease progression  ...  A revised airway epithelial hierarchy includes CFTR-expressing ionocytes. Nature 560, 319-324 (2018). 33. Peng, Y.-R. et al.  ... 
doi:10.1101/2021.03.19.436212 pmid:34845454 pmcid:PMC8629197 fatcat:mtt7gx3tgjgcpelgwtgzt2v4zy

Lineage tracing on transcriptional landscapes links state to fate during differentiation [article]

Caleb Weinreb, Alejo E Rodriguez-Fraticelli, Fernando D Camargo, Allon M Klein
2018 bioRxiv   pre-print
Our analysis identifies functional boundaries of cell potential early in the hematopoietic hierarchy and locates them on a continuous transcriptional landscape.  ...  Here, we use expressed DNA barcodes to clonally trace single cell transcriptomes dynamically during differentiation and apply this approach to the study of hematopoiesis.  ...  A revised airway epithelial hierarchy includes CFTR-expressing ionocytes. Nature 560, 319-324, doi:10.1038/s41586-018-0393-7 (2018). 15 Lu, R., Neff, N. F., Quake, S. R. & Weissman, I. L.  ... 
doi:10.1101/467886 fatcat:nc5vbsqpt5fptozrjxvbo7d5oq

Cell type classification and discovery across diseases, technologies and tissues reveals conserved gene signatures and enables standardized single-cell readouts [article]

Mathew Chamberlain, Richa Hanamsagar, Frank O. Nestle, Emanuele de Rinaldis, Virginia Savova
2021 bioRxiv   pre-print
Here, we present a novel machine learning approach, Signac, which uses neural networks trained with flow-sorted gene expression data to classify cellular phenotypes in single cell RNA-sequencing data.  ...  Autoimmune diseases are a major cause of mortality. Current treatments often yield severe insult to host tissue.  ...  A single-cell atlas of the airway epithelium reveals the CFTR-rich pulmonary ionocyte. 5 Nature 560, 377-381 (2018). 35.  ... 
doi:10.1101/2021.02.01.429207 fatcat:476fjjwbojdnxf2gqpgbq34gbe

Highly Efficient, Massively-Parallel Single-Cell RNA-Seq Reveals Cellular States and Molecular Features of Human Skin Pathology [article]

Travis K. Hughes, Marc H. Wadsworth, Todd M. Gierahn, Tran Do, David Weiss, Priscilla R. Andrade, Feiyang Ma, Bruno J. de Andrade Silva, Shuai Shao, Lam C. Tsoi, Jose Ordovas-Montanes, Johann E. Gudjonsson (+3 others)
2019 bioRxiv   pre-print
Our work presents an essential methodological advance as well as a valuable resource for studying the cellular and molecular features that inform human skin inflammation.  ...  Here, we describe a substantially improved massively-parallel scRNA-Seq protocol we term Seq-Well S^3 ("Second-Strand Synthesis") that increases the efficiency of transcript capture and gene detection  ...  A revised airway epithelial hierarchy includes CFTR-621 expressing ionocytes.  ... 
doi:10.1101/689273 fatcat:hy57jncmdre7jk7p3swu3sgtxq