Dissecting the human immune system with single cell RNA sequencing technology

Xu, Gang; Liu, Yang; Li, Hanjie; Liu, Lei; Zhang, Shuye; Zhang, Zheng

doi:10.1002/jlb.5mr1019-179r

Cited by 15 publications

(8 citation statements)

References 119 publications

(204 reference statements)

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“…We propose that characterizing the earlier immune events and longitudinal analysis of immune dynamics of the infected patients may help gain more insights. These emerging high dimensional techniques, like scRNA-seq, mass cytometry and multiplex imaging tools [28, 29], will greatly improve human immunology studies using minimal precious tissue samples.…”

Section: Discussionmentioning

confidence: 99%

The landscape of lung bronchoalveolar immune cells in COVID-19 revealed by single-cell RNA sequencing

Liao

Liu

Yuan

et al. 2020

Preprint

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167

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The novel coronavirus SARS-CoV-2, etiological agent of recently named Coronavirus infected disease (COVID-19) by WHO, has caused more than 2, 000 deaths worldwide since its emergency in Wuhan City, Hubei province, China, in December, 2019. The symptoms of COVID-19 varied from modest, mild to acute respiratory distress syndrome (ARDS), and the latter of which is generally associated with deregulated immune cytokine production; however, we currently know little as to the interplay between the extent of clinical symptoms and the compositions of lung immune microenvironment. Here, we comprehensively characterized the lung immune microenvironment with the bronchoalveolar lavage fluid (BALF) from 3 severe and 3 mild COVID-19 patients and 8 previously reported healthy lung controls through single-cell RNA sequence (scRNA-seq) combined with TCR-seq. Our data shows that monocyte-derived FCN1+ macrophages, whereas notFABP4+ alveolar macrophages that represent a predominant macrophage subset in BALF from patients with mild diseases, overwhelm in the severely damaged lungs from patients with ARDS. These cells are highly inflammatory and enormous chemokine producers implicated in cytokine storm. Furthermore, the formation of tissue resident, highly expanded clonal CD8+ T cells in the lung microenvironment of mild symptom patients suggests a robust adaptive immune response connected to a better control of COVID-19. This study first reported the cellular atlas of lung bronchoalveolar immune microenvironment in COVID-19 patients at the single-cell resolution, and unveiled the potential immune mechanisms underlying disease progression and protection in COVID-19.

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Section: Discussionmentioning

confidence: 99%

The landscape of lung bronchoalveolar immune cells in COVID-19 revealed by single-cell RNA sequencing

Liao

Liu

Yuan

et al. 2020

Preprint

Self Cite

167

205

View full text Add to dashboard Cite

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“…Recent developments in single-cell technologies on the transcriptional and protein level have rapidly advanced our understanding of the heterogeneity of the human immune system. 5 While protein analyses still suffer from limitations, e.g., in terms of cell number requirements, single-cell RNA-sequencing (scRNA-seq) enables an unbiased, transcriptomewide analysis of even small numbers of cells. So far, scRNA-seq of specific subsets of ILCs (NK cells, 6 ILC2 7 ) or in specific tissues 8,9 has been performed in mice.…”

Section: Introductionmentioning

confidence: 99%

Tissue-specific transcriptional imprinting and heterogeneity in human innate lymphoid cells revealed by full-length single-cell RNA-sequencing

et al. 2021

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The impact of the microenvironment on innate lymphoid cell (ILC)-mediated immunity in humans remains largely unknown. Here we used full-length Smart-seq2 single-cell RNA-sequencing to unravel tissue-specific transcriptional profiles and heterogeneity of CD127+ ILCs across four human tissues. Correlation analysis identified gene modules characterizing the migratory properties of tonsil and blood ILCs, and signatures of tissue-residency, activation and modified metabolism in colon and lung ILCs. Trajectory analysis revealed potential differentiation pathways from circulating and tissue-resident naïve ILCs to a spectrum of mature ILC subsets. In the lung we identified both CRTH2+ and CRTH2− ILC2 with lung-specific signatures, which could be recapitulated by alarmin-exposure of circulating ILC2. Finally, we describe unique TCR-V(D)J-rearrangement patterns of blood ILC1-like cells, revealing a subset of potentially immature ILCs with TCR-δ rearrangement. Our study provides a useful resource for in-depth understanding of ILC-mediated immunity in humans, with implications for disease.

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“…In recent years, with the development of technology, single-cell sequencing ( Wen and Tang, 2016 ; Xu et al, 2020 ), spatial transcriptomics sequencing ( Zhou Y. et al, 2020 ) and ubiquitin mass spectrometry technologies ( Ohtake, 2020 ) have matured. Accurate verification can be performed at the single-cell level, RNA level, and protein level.…”

Section: Discussionmentioning

confidence: 99%

Deubiquitinating Enzymes Orchestrate the Cancer Stem Cell-Immunosuppressive Niche Dialogue: New Perspectives and Therapeutic Potential

Guo

Xia

Deng

et al. 2021

Front. Cell Dev. Biol.

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Cancer stem cells (CSCs) are sparks for igniting tumor recurrence and the instigators of low response to immunotherapy and drug resistance. As one of the important components of tumor microenvironment, the tumor associated immune microenvironment (TAIM) is driving force for the heterogeneity, plasticity and evolution of CSCs. CSCs create the inhibitory TAIM (ITAIM) mainly through four stemness-related signals (SRSs), including Notch-nuclear factor-κB axis, Hedgehog, Wnt and signal transducer and activator of transcription. Ubiquitination and deubiquitination in proteins related to the specific stemness of the CSCs have a profound impact on the regulation of ITAIM. In regulating the balance between ubiquitination and deubiquitination, it is crucial for deubiquitinating enzymes (DUBs) to cleave ubiquitin chains from substrates. Ubiquitin-specific peptidases (USPs) comprise the largest family of DUBs. Growing evidence suggests that they play novel functions in contribution of ITAIM, including regulating tumor immunogenicity, activating stem cell factors, upregulating the SRSs, stabilizing anti-inflammatory receptors, and regulating anti-inflammatory cytokines. These overactive or abnormal signaling may dampen antitumor immune responses. The inhibition of USPs could play a regulatory role in SRSs and reversing ITAIM, and also have great potential in improving immune killing ability against tumor cells, including CSCs. In this review, we focus on the USPs involved in CSCs signaling pathways and regulating ITAIM, which are promising therapeutic targets in antitumor therapy.

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Dissecting the human immune system with single cell RNA sequencing technology

Cited by 15 publications

References 119 publications

The landscape of lung bronchoalveolar immune cells in COVID-19 revealed by single-cell RNA sequencing

The landscape of lung bronchoalveolar immune cells in COVID-19 revealed by single-cell RNA sequencing

Tissue-specific transcriptional imprinting and heterogeneity in human innate lymphoid cells revealed by full-length single-cell RNA-sequencing

Deubiquitinating Enzymes Orchestrate the Cancer Stem Cell-Immunosuppressive Niche Dialogue: New Perspectives and Therapeutic Potential

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