Spatial and temporal localization of immune transcripts defines hallmarks and diversity in the tuberculosis granuloma

Carow, Berit; Hauling, Thomas; Qian, Xiaoyan; Kramnik, Igor; Nilsson, Mats; Rottenberg, Martı́n E.

doi:10.1038/s41467-019-09816-4

Cited by 65 publications

(71 citation statements)

References 60 publications

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“…As discussed above, intestinal epithelial cell RNA localization helps regulate local protein production along the apicobasal axis 61 (Figure 2C). Consequences of disrupting RNA localization in these cell types may underlie disease states such as inflammatory bowel disease, maldigestion or local immune responses 162, 163 …”

Section: Clinical Relevancementioning

confidence: 99%

Mechanisms and consequences of subcellularRNAlocalization across diverse cell types

Engel

Arora

Goering

et al. 2020

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Essentially all cells contain a variety of spatially restricted regions that are important for carrying out specialized functions. Often, these regions contain specialized transcriptomes that facilitate these functions by providing transcripts for localized translation. These transcripts play a functional role in maintaining cell physiology by enabling a quick response to changes in the cellular environment. Here, we review how RNA molecules are trafficked within cells, with a focus on the subcellular locations to which they are trafficked, mechanisms that regulate their transport and clinical disorders associated with misregulation of the process. K E Y W O R D SRNA binding protein, RNA cis-element, RNA localization, RNA transport, zipcode

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Section: Clinical Relevancementioning

confidence: 99%

Mechanisms and consequences of subcellularRNAlocalization across diverse cell types

Engel

Arora

Goering

et al. 2020

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“…In fact, multiplexed in situ imaging of cytokine and immune effector transcripts in TB infected Kramnik mice showed that cellular granulomas displayed networks, like CD68 -iNOS (inducible nitric oxide synthase) and IFNG (gamma interferon), associated with a robust response against M. tuberculosis [ 95 ]. This is in stark contrast to enriched transcript signatures found in necrotic granulomas, such as IL10 and FOXP3 , which are associated with immunosuppression [95] . Additional studies using the Kramnik model should consider mapping immune transcripts in multiple granulomas that are responsive and refractory to PZA treatment.…”

Section: Pza and The Host Environmentmentioning

confidence: 99%

Impact of the host environment on the antitubercular action of pyrazinamide

Lamont

Baughn

2019

eBioMedicine

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a b s t r a c tPyrazinamide remains the only drug in the tuberculosis pharmacopeia to drastically shorten first-line therapy from nine to six months. Due to its unparalleled ability to sterilize non-replicating bacilli and reduce relapse rates, PZA is expected to be irreplaceable in future therapies against tuberculosis. While the molecular target of PZA is unclear, recent pharmacokinetic studies using small animal models and patient samples have highlighted the importance of host metabolism and immune responses in PZA efficacy. Delineating which host factors are important for PZA action will be integral to the design of next-generation therapies to shorten current TB drug regimens as well as to overcome treatment limitations in some patients. In this review, we discuss evidence for influence of the host environment on PZA activity, targets for PZA mechanism of action, recent studies in PZA pharmacokinetics, PZA antagonism and synergy with other first-line anti-TB drugs, and implications for future research.

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“…All code is written in MATLAB and is freely available at (https://github.com/Moldia). Many steps follow previous publications 20,21,29,30 .…”

Section: Imagingmentioning

confidence: 99%

Hybridization-based In Situ Sequencing (HybISS): spatial transcriptomic detection in human and mouse brain tissue

Gyllborg

Langseth

Qian

et al. 2020

Preprint

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Visualization of the transcriptome in situ has proven to be a valuable tool in exploring single-cell RNAsequencing data, providing an additional dimension to investigate spatial cell typing and cell atlases, disease architecture or even data driven discoveries. The field of spatially resolved transcriptomic technologies is emerging as a vital tool to profile gene-expression, continuously pushing current methods to accommodate larger gene panels and larger areas without compromising throughput efficiency. Here, we describe a new version of the in situ sequencing (ISS) method based on padlock probes and rolling circle amplification. Modifications in probe design allows for a new barcoding system via sequence-by-hybridization chemistry for improved spatial detection of RNA transcripts. Due to the amplification of probes, amplicons can be visualized with standard epifluorescence microscopes with high-throughput efficiency and the new sequencing chemistry removes limitations bound by sequence-by-ligation chemistry of ISS. Here we present hybridization-based in situ sequencing (HybISS) that allows for increased flexibility and multiplexing, increased signal-to-noise, all without compromising throughput efficiency of imaging large fields of view. Moreover, the current protocol is demonstrated to work on human brain tissue samples, a source that has proven to be difficult to work with image-based spatial analysis techniques. Overall, HybISS technology works as a target amplification detection method for improved spatial transcriptomic visualization, and importantly, with an ease of implementation.

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Spatial and temporal localization of immune transcripts defines hallmarks and diversity in the tuberculosis granuloma

Cited by 65 publications

References 60 publications

Mechanisms and consequences of subcellularRNAlocalization across diverse cell types

Mechanisms and consequences of subcellularRNAlocalization across diverse cell types

Impact of the host environment on the antitubercular action of pyrazinamide

Hybridization-based In Situ Sequencing (HybISS): spatial transcriptomic detection in human and mouse brain tissue

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