The human gastrointestinal tract-specific transcriptome and proteome as defined by RNA sequencing and antibody-based profiling

Gremel, Gabriela; Wanders, Alkwin; Cedernaes, Jonathan; Fagerberg, Linn; Hallström, Björn M.; Edlund, Karolina; Sjöstedt, Evelina; Uhlén, Mathias; Pontén, Fredrik

doi:10.1007/s00535-014-0958-7

Cited by 61 publications

(51 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The tissues with the most mRNAs highly enriched (at least 5× the levels in all other tissues) are testis (999) and brain (318). Several tissue-specific HPA publications have been published, and more are expected during 2015 with tissue-specific immunohistochemical and transcript evidence to guide specimen selection for further MS studies, for example, describing the brain, 18 liver, 19 testis, 20 kidney, 21 pancreas, 22 skin, 23 adipose tissue, 24 gallbladder, 25 lung, 26 gastrointestinal tract, 27 and cardiac and skeletal muscle. 28 HPA, v14, will be released in Fall 2015 along with a novel Rodent Brain Atlas comprising immunofluorescently stained whole-mouse-brain sections.…”

Section: A New Phase For the Human Protein Atlasmentioning

confidence: 99%

Metrics for the Human Proteome Project 2015: Progress on the Human Proteome and Guidelines for High-Confidence Protein Identification

et al. 2015

View full text Add to dashboard Cite

Remarkable progress continues on the annotation of the proteins identified in the Human Proteome and on finding credible proteomic evidence for the expression of “missing proteins”. Missing proteins are those with no previous protein-level evidence or insufficient evidence to make a confident identification upon reanalysis in PeptideAtlas and curation in neXtProt. Enhanced with several major new data sets published in 2014, the human proteome presented as neXtProt, version 2014-09-19, has 16 491 unique confident proteins (PE level 1), up from 13 664 at 2012-12 and 15 646 at 2013-09. That leaves 2948 missing proteins from genes classified having protein existence level PE 2, 3, or 4, as well as 616 dubious proteins at PE 5. Here, we document the progress of the HPP and discuss the importance of assessing the quality of evidence, confirming automated findings and considering alternative protein matches for spectra and peptides. We provide guidelines for proteomics investigators to apply in reporting newly identified proteins.

show abstract

Section: A New Phase For the Human Protein Atlasmentioning

confidence: 99%

Metrics for the Human Proteome Project 2015: Progress on the Human Proteome and Guidelines for High-Confidence Protein Identification

et al. 2015

View full text Add to dashboard Cite

show abstract

“…NLRP6 is predominantly expressed in intestinal epithelial cells, including goblet cells (Elinav et al, 2011; Gremel et al, 2014; Wlodarska et al, 2014), where it was found to be essential for mucosal self-renewal, proliferation, and mucus secretion (Chen et al, 2011; Normand et al, 2011; Wlodarska et al, 2014). Likewise, ASC and caspase-1 are co-expressed in intestinal epithelial cells, yet no biochemical evidence of their assembly into an NLRP6 inflammasome has been demonstrated to date.…”

Section: Introductionmentioning

confidence: 99%

Microbiota-Modulated Metabolites Shape the Intestinal Microenvironment by Regulating NLRP6 Inflammasome Signaling

Levy

Thaiss

Zeevi

et al. 2015

Cell

786

787

View full text Add to dashboard Cite

Host-microbiome co-evolution drives homeostasis and disease susceptibility, yet regulatory principles governing the integrated intestinal host-commensal microenvironment remain obscure. While inflammasome signaling participates in these interactions, its activators and microbiome-modulating mechanisms are unknown. Here, we demonstrate that the microbiota-associated metabolites taurine, histamine, and spermine shape the host-microbiome interface by co-modulating NLRP6 inflammasome signaling, epithelial IL-18 secretion, and downstream anti-microbial peptide (AMP) profiles. Distortion of this balanced AMP landscape by inflammasome deficiency drives dysbiosis development. Upon fecal transfer, colitis-inducing microbiota hijacks this microenvironment-orchestrating machinery through metabolite-mediated inflammasome suppression, leading to distorted AMP balance favoring its preferential colonization. Restoration of the metabolite-inflammasome-AMP axis reinstates a normal microbiota and ameliorates colitis. Together, we identify microbial modulators of the NLRP6 inflammasome and highlight mechanisms by which microbiome-host interactions cooperatively drive microbial community stability through metabolite-mediated innate immune modulation. Therefore, targeted ‘postbiotic’ metabolomic intervention may restore a normal microenvironment, as treatment or prevention of dysbiosis-driven diseases.

show abstract

“…Most of the studies intended to define the expression and function of NLRP6 have been performed in mouse models and very little research to date has involved human patients. Consistent with the mouse model, genome-wide analysis based on gastrointestinal transcriptomics revealed high expression of NLRP6 in the small intestine of healthy humans, 64 suggesting that NLRP6 might also have a specific role in the intestines of humans. Recently, we reported higher expression of NLRP6 in neutrophils, macrophages, and epithelial cells in the lungs obtained from pneumonia patients.…”

Section: Nlrp6 In Human Diseasesmentioning

confidence: 63%

The NLRP6 inflammasome in health and disease

et al. 2020

View full text Add to dashboard Cite

NACHT, LRR (leucine-rich repeat), and PYD (pyrin domain) domain-containing 6 (Nlrp6) is a member of the NLR (nucleotideoligomerization domain-like receptor) family that patrols the cytosolic compartment of cells to detect pathogen-and damageassociated molecular patterns. Because Nlrp6 is a recently discovered inflammasome, details of its signaling mechanism, structural assembly, and roles in host defense have yet to be determined. To date, Nlrp6 has been proposed to perform a multitude of functions ranging from control of microbiota, maintenance of epithelial integrity, and regulation of metabolic diseases to modulation of host defense during microbial infections, cancer protection, and regulation of neuroinflammation. While recent studies have questioned some of the proposed functions of Nlrp6, Nlrp6 has been shown to form an inflammasome complex and cleaves interleukin-1β (IL-1β) and IL-18 during microbial infection, indicating that it is a bonafide inflammasome. In this review, we summarize the recent advancements in knowledge of the signaling mechanisms and structure of the Nlrp6 inflammasome and discuss the relevance of NLRP6 to human disease.

show abstract

The human gastrointestinal tract-specific transcriptome and proteome as defined by RNA sequencing and antibody-based profiling

Cited by 61 publications

References 50 publications

Metrics for the Human Proteome Project 2015: Progress on the Human Proteome and Guidelines for High-Confidence Protein Identification

Metrics for the Human Proteome Project 2015: Progress on the Human Proteome and Guidelines for High-Confidence Protein Identification

Microbiota-Modulated Metabolites Shape the Intestinal Microenvironment by Regulating NLRP6 Inflammasome Signaling

The NLRP6 inflammasome in health and disease

Contact Info

Product

Resources

About