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

Salahudeen, Ameen A.; Choi, Stacey S.; Rustagi, Arjun; Zhu, Junjie; Unen, Vincent van; O, Sean de la; Flynn, Ryan A.; Margalef-Català, Mar; Santos, António J. M.; Ju, Jihang; Batish, Arpit; Usui, Tatsuya; Zheng, Grace; Edwards, Caitlin E.; Wagar, Lisa E.; Luca, Vincent C.; Anchang, Benedict; Nagendran, Monica; Nguyen, Khanh Cong; Hart, Daniel J.; Terry, Jessica M.; Belgrader, Phillip; Ziraldo, Solongo B.; Mikkelsen, Tarjei S.; Harbury, Pehr B.; Glenn, Jeffrey S.; García, K. Christopher; Davis, Mark M.; Baric, Ralph S.; Sabatti, Chiara; Amieva, Manuel R.; Blish, Catherine A.; Desai, Tushar J.; Kuo, Calvin J.

doi:10.1038/s41586-020-3014-1

Cited by 311 publications

(341 citation statements)

References 47 publications

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“…After excluding immune cells and putative doublets, we identified 30,700 cells that clustered into 17 distinct epithelial, endothelial, and stromal cell types (Figures S4A-S4C). Prior studies have demonstrated that multiple lung cell types express the SARS-CoV-2 entry receptor, ACE2, and the serine protease, TMPRSS2, including epithelial basal, club, and ciliated cells, and alveolar type 1 (AT-1) and 2 (AT-2) cells (Hou et al, 2020;Salahudeen et al, 2020;Sungnak et al, 2020). Human bronchial epithelial cell (HBEC) cultures have shown that ciliated cells may be the initial target of infection, which can later spread to other cell types (Ravindra et al, 2020).…”

Section: Chirp-ms Of Sars-cov-2 Viral Rna In Infected Mammalian Cellsmentioning

confidence: 99%

Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions

Flynn

Belk

et al. 2021

Cell

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173

199

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Section: Chirp-ms Of Sars-cov-2 Viral Rna In Infected Mammalian Cellsmentioning

confidence: 99%

Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions

Flynn

Belk

et al. 2021

Cell

Self Cite

173

199

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“…It has also been found that human hepatocyte and cholangiocyte organoids show permissive conditions for the culture of SARS-CoV-2 (Chandar et al, 2020). It has been found that hPSC-derived cells/organoids show similar chemokine responses as occurs in COVID-19 tissues ; (Salahudeen et al, 2020).…”

Section: Human Pluripotent Stem Cell-based Platformmentioning

confidence: 93%

SARS-CoV-2: Pathogenesis, Molecular Targets and Experimental Models

Kanimozhi¹,

Pradhapsingh

Pawar

et al. 2021

Front. Pharmacol.

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recent pandemic outbreak threatening human beings worldwide. This novel coronavirus disease-19 (COVID-19) infection causes severe morbidity and mortality and rapidly spreading across the countries. Therefore, there is an urgent need for basic fundamental research to understand the pathogenesis and druggable molecular targets of SARS-CoV-2. Recent sequencing data of the viral genome and X-ray crystallographic data of the viral proteins illustrate potential molecular targets that need to be investigated for structure-based drug design. Further, the SARS-CoV-2 viral pathogen isolated from clinical samples needs to be cultivated and titrated. All of these scenarios demand suitable laboratory experimental models. The experimental models should mimic the viral life cycle as it happens in the human lung epithelial cells. Recently, researchers employing primary human lung epithelial cells, intestinal epithelial cells, experimental cell lines like Vero cells, CaCo-2 cells, HEK-293, H1299, Calu-3 for understanding viral titer values. The human iPSC-derived lung organoids, small intestinal organoids, and blood vessel organoids increase interest among researchers to understand SARS-CoV-2 biology and treatment outcome. The SARS-CoV-2 enters the human lung epithelial cells using viral Spike (S1) protein and human angiotensin-converting enzyme 2 (ACE-2) receptor. The laboratory mouse show poor ACE-2 expression and thereby inefficient SARS-CoV-2 infection. Therefore, there was an urgent need to develop transgenic hACE-2 mouse models to understand antiviral agents’ therapeutic outcomes. This review highlighted the viral pathogenesis, potential druggable molecular targets, and suitable experimental models for basic fundamental research.

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“…To reach this goal, they used a 3D organoid in vitro model to simulate distal human lung in which basal stem cells and AT2 cells were cultured. After 26 days of culture , the lung organoid demonstrated the differentiation, and proliferation of different cell types including ACE2 receptor expressing cells [88]. Further, Yang et al designed an in vitro platform using hPSCs, islets, and hepatocyte cells through which they found a relation between diabetes and SARS-CoV-2 infection.…”

Section: Organoids (Biomaterials-based)mentioning

confidence: 99%

Role of biomaterials in the diagnosis, prevention, treatment, and study of corona virus disease 2019 (COVID-19)

et al. 2021

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Recently emerged novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resulting corona virus disease 2019 (COVID-19) led to urgent search for methods to prevent and treat COVID-19. Among important disciplines that were mobilized is the biomaterials science and engineering. Biomaterials offer a range of possibilities to develop disease models, protective, diagnostic, therapeutic, monitoring measures, and vaccines. Among the most important contributions made so far from this field are tissue engineering, organoids, and organ-on-a-chip systems, which have been the important frontiers in developing tissue models for viral infection studies. Also, due to low bioavailability and limited circulation time of conventional antiviral drugs, controlled and targeted drug delivery could be applied alternatively. Fortunately, at the time of writing this paper, we have two successful vaccines and new at-home detection platforms. In this paper, we aim to review recent advances of biomaterial-based platforms for protection, diagnosis, vaccination, therapeutics, and monitoring of SARS-CoV-2 and discuss challenges and possible future research directions in this field.

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

Cited by 311 publications

References 47 publications

Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions

Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions

SARS-CoV-2: Pathogenesis, Molecular Targets and Experimental Models

Role of biomaterials in the diagnosis, prevention, treatment, and study of corona virus disease 2019 (COVID-19)

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