Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes. We used this approach to explore the human secretome, the membrane proteome, the druggable proteome, the cancer proteome, and the metabolic functions in 32 different tissues and organs. All the data are integrated in an interactive Web-based database that allows exploration of individual proteins, as well as navigation of global expression patterns, in all major tissues and organs in the human body.

Tissue-based map of the human proteome

A large body of literature is available on wound healing in humans. Nonetheless, a standardized ex vivo wound model without disruption of the dermal compartment has not been put forward with compelling justification. Here, we present a novel wound model based on application of negative pressure and its effects for epidermal regeneration and immune cell behaviour. Importantly, the basement membrane remained intact after blister roof removal and keratinocytes were absent in the wounded area. Upon six days of culture, the wound was covered with one to three-cell thick K14+Ki67+ keratinocyte layers, indicating that proliferation and migration were involved in wound closure. After eight to twelve days, a multi-layered epidermis was formed expressing epidermal differentiation markers (K10, filaggrin, DSG-1, CDSN). Investigations about immune cell-specific manners revealed more T cells in the blister roof epidermis compared to normal epidermis. We identified several cell populations in blister roof epidermis and suction blister fluid that are absent in normal epidermis which correlated with their decrease in the dermis, indicating a dermal efflux upon negative pressure. Together, our model recapitulates the main features of epithelial wound regeneration, and can be applied for testing wound healing therapies and investigating underlying mechanisms.

/pdf/re-epithelialization-and-immune-cell-behaviour-in-an-ex-vivo-3lsvtwo6xm.pdf

Re-epithelialization and immune cell behaviour in an ex vivo human skin model.

Protein expression across human tissues Sequencing the human genome gave new insights into human biology and disease. However, the ultimate goal is to understand the dynamic expression of each of the approximately 20,000 protein-coding genes and the function of each protein. Uhlén et al. now present a map of protein expression across 32 human tissues. They not only measured expression at an RNA level, but also used antibody profiling to precisely localize the corresponding proteins. An interactive website allows exploration of expression patterns across the human body. Science, this issue 10.1126/science.1260419 Transcriptomics and immunohistochemistry map protein expression across 32 human tissues. INTRODUCTION Resolving the molecular details of proteome variation in the different tissues and organs of the human body would greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on quantitative transcriptomics on a tissue and organ level combined with protein profiling using microarray-based immunohistochemistry to achieve spatial localization of proteins down to the single-cell level. We provide a global analysis of the secreted and membrane proteins, as well as an analysis of the expression profiles for all proteins targeted by pharmaceutical drugs and proteins implicated in cancer. RATIONALE We have used an integrative omics approach to study the spatial human proteome. Samples representing all major tissues and organs (n = 44) in the human body have been analyzed based on 24,028 antibodies corresponding to 16,975 protein-encoding genes, complemented with RNA-sequencing data for 32 of the tissues. The antibodies have been used to produce more than 13 million tissue-based immunohistochemistry images, each annotated by pathologists for all sampled tissues. To facilitate integration with other biological resources, all data are available for download and cross-referencing. RESULTS We report a genome-wide analysis of the tissue specificity of RNA and protein expression covering more than 90% of the putative protein-coding genes, complemented with analyses of various subproteomes, such as predicted secreted proteins (n = 3171) and membrane-bound proteins (n = 5570). The analysis shows that almost half of the genes are expressed in all analyzed tissues, which suggests that the gene products are needed in all cells to maintain “housekeeping” functions such as cell growth, energy generation, and basic metabolism. Furthermore, there is enrichment in metabolism among these genes, as 60% of all metabolic enzymes are expressed in all analyzed tissues. The largest number of tissue-enriched genes is found in the testis, followed by the brain and the liver. Analysis of the 618 proteins targeted by clinically approved drugs unexpectedly showed that 30% are expressed in all analyzed tissues. An analysis of metabolic activity based on genome-scale metabolic models (GEMS) revealed liver as the most metabolically active tissue, followed by adipose tissue and skeletal muscle. CONCLUSIONS A freely available interactive resource is presented as part of the Human Protein Atlas portal (www.proteinatlas.org), offering the possibility to explore the tissue-elevated proteomes in tissues and organs and to analyze tissue profiles for specific protein classes. Comprehensive lists of proteins expressed at elevated levels in the different tissues have been compiled to provide a spatial context with localization of the proteins in the subcompartments of each tissue and organ down to the single-cell level. The human tissue–enriched proteins. All tissue-enriched proteins are shown for 13 representative tissues or groups of tissues, stratified according to their predicted subcellular localization. Enriched proteins are mainly intracellular in testis, mainly membrane bound in brain and kidney, and mainly secreted in pancreas and liver. Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray–based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes. We used this approach to explore the human secretome, the membrane proteome, the druggable proteome, the cancer proteome, and the metabolic functions in 32 different tissues and organs. All the data are integrated in an interactive Web-based database that allows exploration of individual proteins, as well as navigation of global expression patterns, in all major tissues and organs in the human body.

A Tissue-Based Map of the Human Proteome

Virus-like particle (VLP) technology is a promising approach for the construction of novel vaccines, diagnostic tools, and gene therapy vectors. Initially, VLPs were primarily derived from non-enveloped icosahedral or helical viruses and proved to be viable vaccine candidates due to their effective presentation of epitopes in a native conformation. VLP technology has also been used to prepare chimeric VLPs decorated with genetically fused or chemically coupled epitope stretches selected from immunologically defined target proteins. However, structural constraints associated with the rigid geometrical architecture of icosahedral or helical VLPs pose challenges for the expression and presentation of large epitopes. Complex VLPs derived from non-symmetric enveloped viruses are increasingly being used to incorporate large epitopes and even full-length foreign proteins. Pleomorphic VLPs derived from influenza or other enveloped viruses can accommodate multiple full-length and/or chimeric proteins that can be rationally designed for multifunctional purposes, including multivalent vaccines. Therefore, a second generation of VLP carriers is represented by complex particles reconstructed from natural or chimeric structural proteins derived from complex enveloped viruses. Further development of safe and efficient VLP nanotechnology may require a rational combination of both approaches.

/pdf/development-of-virus-like-particle-technology-from-small-269frj4qqh.pdf

Development of Virus-Like Particle Technology from Small Highly Symmetric to Large Complex Virus-Like Particle Structures

Background/Aims: The association between postoperative infection and prolonged survival in high-grade glioma is still a matter of debate. Previously we demonstrated that the intracerebral (i.c.) injection of heat-inactivated staphylococcal epitopes (HISE) resulted in a well-defined infux of immunocompetent cells across the blood-brain barrier. The present study investigated the potential antitumoral effect of HISE-immunostimulation in an experimental glioma model. Methods: Wistar rats were intracerebrally implanted with 9L gliosarcoma cells (n=6), 9L cells mixed with HISE (n=12), or phosphate buffered saline (n=4). Tumor growth was measured by serial magnetic resonance imaging (MRI). After death due to the tumor burden, the brains were histopathologically assessed for inflammation and oncolysis. A toxicity assay was performed to quantify potential impairment of HISE on tumor cell growth in vitro. Results: Animals treated by HISE showed a significant increase in average survival and even complete regression of an already established mass in one case. Naive 9L gliosarcomas failed to recruit significant numbers of systemic immune cells. In contrast, concomitant intracerebral HISE inoculation lead to a oncolysis and a distinct peri- and intratumoral infiltration of macrophages, CD8 and CD4 co-expressing T-lymphocytes in two thirds of the tumor-bearing animals. The toxicity screening showed HISE-mediated oncolysis to be ineffective ex vivo. Conclusion: This study describes a novel approach for combatting malignant glioma using inactivated staphylococci as potent immunomodulators. Our results provide an outline for investigating the strategic potential of bacteria as emerging future therapeutics.

/pdf/intracerebral-administration-of-heat-inactivated-2kc7ujt3yz.pdf

Intracerebral Administration of Heat-Inactivated Staphylococcus Epidermidis Enhances Oncolysis and Prolongs Survival in a 9L Orthotopic Gliosarcoma Model

CCR8 : nouvelle cible thérapeutique dans les lymphomes T cutanés

Detection of a T cell receptor δ chain with an anti-TCR α chain serum

Early detection of relapse in Sézary syndrome: the added value of KIR3DL2, T-plastin, Twist and Tox for clinical routine

Antikörper gegen humanes cd39 und verwendung davon zur hemmung der regulatorischen t-zell-aktivität

The present disclosure relates to antibodies having specificity to myosin 18A and uses thereof. In particular, the present disclosure relates to an antibody having specificity to myosin 18A comprising a heavy chain comprising i) a H-CDR1 having at least 90% of identity with the H-CDR1 of DY12, ii) a H-CDR2 having at least 90% of identity with the H-CDR2 of DY12 and iii) a H-CDR3 having at least 90% of identity with the H-CDR3 of DY12 and a light chain comprising i) a L- CDR1 having at least 90% of identity with the L-CDR1 of DY12, ii) a L- CDR2 having at least 90% of identity with the L-CDR2 of DY12 and iii) a L-CDR3 having at least 90% of identity with the L-CDR3 of DY12.

Antibodies having specificity to myosin 18a and uses thereof

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CCR8 : nouvelle cible thérapeutique dans les lymphomes T cutanés

Detection of a T cell receptor δ chain with an anti-TCR α chain serum

Early detection of relapse in Sézary syndrome: the added value of KIR3DL2, T-plastin, Twist and Tox for clinical routine

Antikörper gegen humanes cd39 und verwendung davon zur hemmung der regulatorischen t-zell-aktivität

Antibodies having specificity to myosin 18a and uses thereof