A cell atlas of human thymic development defines T cell repertoire formation

Park, Jong-Eun; Botting, Rachel A.; Conde, Cecilia Domínguez; Popescu, Dorin-Mirel; Lavaert, Marieke; Kunz, Daniel J.; Goh, Issac; Stephenson, Emily; Ragazzini, Roberta; Tuck, Elizabeth; Wilbrey-Clark, Anna; Roberts, Kenny; Kedlian, Veronika R.; Ferdinand, John R.; He, Xiaoling; Webb, Simone; Maunder, Daniel; Vandamme, Niels; Mahbubani, Krishnaa; Polański, Krzysztof; Mamanova, Lira; Bolt, Liam; Crossland, David; Rita, Fabrizio De; Fuller, Andrew; Filby, Andrew; Reynolds, Gary; Dixon, David; Saeb‐Parsy, Kourosh; Lisgo, Steven; Henderson, Deborah J.; Vento‐Tormo, Roser; Bayraktar, Ömer; Barker, Roger A.; Meyer, Kerstin B.; Saeys, Yvan; Bonfanti, Paola; Behjati, Sam; Clatworthy, Menna R.; Taghon, Tom; Haniffa, Muzlifah; Teichmann, Sarah A.

doi:10.1126/science.aay3224

Cited by 409 publications

(525 citation statements)

References 70 publications

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“…The placental single-cell transcriptome is available for re-analysis at Human Cell Atlas Data Portal (https://data.humancellatlas.org) or E-MTAB-6701 (https://www.ebi.ac.uk/arrayexpress). We applied this same strategy to investigate the gene expression of our candidates using scRNA-seq in human fetal tissues: lung (43), liver (44), and thymus (45). Last accessed June 2020.…”

Section: Single-cell Transcriptome Analysis Of Human Placentas and Fementioning

confidence: 99%

“…B. Bar plots representing the gene expression (log-transformed normalized counts) of ACE2, TMPRSS2, CTSL, DPP4, DAAM1, and PAICS in human fetal tissues: lung (43), liver (44), and thymus (45). The x-axis indicates log-transformed normalized counts while, Y-axis indicates the number of cells expressing the gene.…”

Section: Supplementary Figure 1 Placenta Gene Expression Profile Ofmentioning

confidence: 99%

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Prediction of non-canonical routes for SARS-CoV-2 infection in human placenta cells

Constantino

Cury

Nogueira

et al. 2020

Preprint

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The SARS-CoV-2 is the causative agent of the COVID-19 pandemic. The data available about COVID-19 during pregnancy have demonstrated placental infection; however, the intrauterine transmission of SARS-CoV-2 is still debated. Intriguingly, while canonical SARS-CoV-2 cell entry mediators are expressed at low levels in placental cells, the receptors for viruses that cause congenital infections such as the cytomegalovirus and Zika virus are highly expressed in these cells. Here we analyzed the transcriptional profile (microarray and single-cell RNA-Seq) of proteins potentially interacting with coronaviruses to identify non-canonical mediators of SARS-CoV-2 infection and replication in the placenta. We show that, despite low levels of the canonical cell entry mediators ACE2 and TMPRSS2, villous trophoblast cells co-express high levels of the potential non-canonical cell-entry mediators DPP4 and CTSL. We also found changes in the expression of DAAM1 and PAICS genes during pregnancy, which are translated into proteins also predicted to interact with coronaviruses proteins. These results provide new insight into the interaction between SARS-CoV-2 and host proteins that may act as non-canonical routes for SARS-CoV-2 infection and replication in the placenta cells.

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Section: Single-cell Transcriptome Analysis Of Human Placentas and Fementioning

confidence: 99%

Section: Supplementary Figure 1 Placenta Gene Expression Profile Ofmentioning

confidence: 99%

Prediction of non-canonical routes for SARS-CoV-2 infection in human placenta cells

Constantino

Cury

Nogueira

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…Therefore, the functions of blood and the immune system are inseparable. T cells and B cells are important in the pathogenesis of many-perhaps all-immune-mediated diseases (14)(15)(16)(17). A T cell receptor (TCR) mediates recognition of pathogen-associated epitopes through interactions with peptide and major histocompatibility complexes (pMHCs).…”

mentioning

confidence: 99%

Blood single cell immune profiling reveals the interferon-MAPK pathway mediated adaptive immune response for COVID-19

Huang

Shi

Gong

et al. 2020

Preprint

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The coronavirus disease 2019 outbreak is an ongoing global health emergence, but the pathogenesis remains unclear. We revealed blood cell immune response profiles using 5' mRNA, TCR and BCR V(D)J transcriptome analysis with single-cell resolution. Data from 134,620 PBMCs and 83,387 TCR and 12,601 BCR clones was obtained, and 56 blood cell subtypes and 23 new cell marker genes were identified from 16 participants. The number of specific subtypes of immune cells changed significantly when compared patients with controls. Activation of the interferon-MAPK pathway is the major defense mechanism, but MAPK transcription signaling is inhibited in cured patients. TCR and BCR V(D)J recombination is highly diverse in generating different antibodies against SARS-CoV-2. Therefore, the interferon-MAPK pathway and TCR-and BCR-produced antibodies play important roles in the COVID-19 immune response. Immune deficiency or immune overresponse may result in the condition of patients with COVID-19 becoming critical or severe.

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“…Ground-breaking single-cell-atlases of development have been further extended to fundamental organs and systems including for example brain, heart, liver, thymus, gut and kidney. For example analysing thymic development at single-cell resolution has deepened understanding of new stromal and epithelial cell states and novel T cell types and indicates new principles of naïve T cell V(D)J repertoire formation, revealing that the human naïve T cell repertoire is biased in its receptor gene segments prior to pathogen exposure 11 .…”

Section: Development Of Single-cell Transcriptomics Technologies Overmentioning

confidence: 99%

Single cell transcriptomics comes of age

2020

Self Cite

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Single cell transcriptomics technologies have vast potential in advancing our understanding of biology and disease. Here, Sarah Aldridge and Sarah Teichmann review the last decade of technological advancements in single-cell transcriptomics and highlight some of the recent discoveries enabled by this technology. The past decade has seen a revolution in single-cell transcriptomics. Here we describe advances made and the transformation that this powerful approach has on our ability to build detailed cellular maps of tissues, gaining unique insights in health and disease.

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A cell atlas of human thymic development defines T cell repertoire formation

Cited by 409 publications

References 70 publications

Prediction of non-canonical routes for SARS-CoV-2 infection in human placenta cells

Prediction of non-canonical routes for SARS-CoV-2 infection in human placenta cells

Blood single cell immune profiling reveals the interferon-MAPK pathway mediated adaptive immune response for COVID-19

Single cell transcriptomics comes of age

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