For a complete understanding of a system's processes and each protein's role in health and disease, it is essential to study protein expression with a spatial resolution, as the exact location of ...proteins at tissue, cellular, or subcellular levels is tightly linked to protein function. The Human Protein Atlas (HPA) project is a large‐scale initiative aiming at mapping the entire human proteome using antibody‐based proteomics and integration of various other omics technologies. The publicly available knowledge resource www.proteinatlas.org is one of the world's most visited biological databases and has been extensively updated during the last few years. The current version is divided into six main sections, each focusing on particular aspects of the human proteome: (a) the Tissue Atlas showing the distribution of proteins across all major tissues and organs in the human body; (b) the Cell Atlas showing the subcellular localization of proteins in single cells; (c) the Pathology Atlas showing the impact of protein levels on survival of patients with cancer; (d) the Blood Atlas showing the expression profiles of blood cells and actively secreted proteins; (e) the Brain Atlas showing the distribution of proteins in human, mouse, and pig brain; and (f) the Metabolic Atlas showing the involvement of proteins in human metabolism. The HPA constitutes an important resource for further understanding of human biology, and the publicly available datasets hold much promise for integration with other emerging efforts focusing on single cell analyses, both at transcriptomic and proteomic level.
The correct spatial distribution of proteins is vital for their function and often mis‐localization or ectopic expression leads to diseases. For more than a decade, the Human Protein Atlas (HPA) has ...constituted a valuable tool for researchers studying protein localization and expression in human tissues and cells. The centerpiece of the HPA is its unique antibody collection for mapping the entire human proteome by immunohistochemistry and immunocytochemistry. By these approaches, more than 10 million images showing protein expression patterns at a single‐cell level were generated and are publicly available at www.proteinatlas.org. The antibody‐based approach is combined with transcriptomics data for an overview of global expression profiles. The present article comprehensively describes the HPA database functions and how users can utilize it for their own research as well as discusses the future path of spatial proteomics.
The novel SARS‐coronavirus 2 (SARS‐CoV‐2) poses a global challenge on healthcare and society. For understanding the susceptibility for SARS‐CoV‐2 infection, the cell type‐specific expression of the ...host cell surface receptor is necessary. The key protein suggested to be involved in host cell entry is angiotensin I converting enzyme 2 (ACE2). Here, we report the expression pattern of ACE2 across > 150 different cell types corresponding to all major human tissues and organs based on stringent immunohistochemical analysis. The results were compared with several datasets both on the mRNA and protein level. ACE2 expression was mainly observed in enterocytes, renal tubules, gallbladder, cardiomyocytes, male reproductive cells, placental trophoblasts, ductal cells, eye, and vasculature. In the respiratory system, the expression was limited, with no or only low expression in a subset of cells in a few individuals, observed by one antibody only. Our data constitute an important resource for further studies on SARS‐CoV‐2 host cell entry, in order to understand the biology of the disease and to aid in the development of effective treatments to the viral infection.
Synopsis
The protein expression profile of ACE2, suggested as host receptor for SARS‐CoV‐2, is assessed in various human organs. Notably, limited ACE2 expression is observed in the respiratory system both on the protein and mRNA level.
Consistent and reliable ACE2 protein expression is found in enterocytes, renal tubules, gallbladder, cardiomyocytes, male reproductive cells, placental trophoblasts, ductal cells, eye and vasculature.
ACE2 expression in the respiratory system is either absent or low in a subset of cells or individuals.
The comprehensive summary of ACE expression in all major human tissues and cell types constitutes an important resource for further studies on SARS‐CoV-2 infection and host cell entry.
The protein expression profile of ACE2, suggested as host receptor for SARS‐CoV‐2, is assessed in various human organs. Notably, limited ACE2 expression is observed in the respiratory system both on the protein and mRNA level.
Blood is the predominant source for molecular analyses in humans, both in clinical and research settings. It is the target for many therapeutic strategies, emphasizing the need for comprehensive ...molecular maps of the cells constituting human blood. In this study, we performed a genome-wide transcriptomic analysis of protein-coding genes in sorted blood immune cell populations to characterize the expression levels of each individual gene across the blood cell types. All data are presented in an interactive, open-access Blood Atlas as part of the Human Protein Atlas and are integrated with expression profiles across all major tissues to provide spatial classification of all protein-coding genes. This allows for a genome-wide exploration of the expression profiles across human immune cell populations and all major human tissues and organs.
The brain, with its diverse physiology and intricate cellular organization, is the most complex organ of the mammalian body. To expand our basic understanding of the neurobiology of the brain and its ...diseases, we performed a comprehensive molecular dissection of 10 major brain regions and multiple subregions using a variety of transcriptomics methods and antibody-based mapping. This analysis was carried out in the human, pig, and mouse brain to allow the identification of regional expression profiles, as well as to study similarities and differences in expression levels between the three species. The resulting data have been made available in an open-access Brain Atlas resource, part of the Human Protein Atlas, to allow exploration and comparison of the expression of individual protein-coding genes in various parts of the mammalian brain.
Quantifying the differential expression of genes in various human organs, tissues, and cell types is vital to understand human physiology and disease. Recently, several large‐scale transcriptomics ...studies have analyzed the expression of protein‐coding genes across tissues. These datasets provide a framework for defining the molecular constituents of the human body as well as for generating comprehensive lists of proteins expressed across tissues or in a tissue‐restricted manner. Here, we review publicly available human transcriptome resources and discuss body‐wide data from independent genome‐wide transcriptome analyses of different tissues. Gene expression measurements from these independent datasets, generated using samples from fresh frozen surgical specimens and postmortem tissues, are consistent. Overall, the different genome‐wide analyses support a distribution in which many proteins are found in all tissues and relatively few in a tissue‐restricted manner. Moreover, we discuss the applications of publicly available omics data for building genome‐scale metabolic models, used for analyzing cell and tissue functions both in physiological and in disease contexts.
Quantifying gene expression in human organs, tissues and cell types is vital to understand physiology and disease. Here we discuss publically available human transcriptome resources and their applications in combination with genome‐scale metabolic models.
The human testis undergoes dramatic developmental and structural changes during puberty, including proliferation and maturation of somatic niche cells, and the onset of spermatogenesis. To ...characterize this understudied process, we profiled and analyzed single-cell transcriptomes of ∼10,000 testicular cells from four boys spanning puberty and compared them to those of infants and adults. During puberty, undifferentiated spermatogonia sequentially expand and differentiate prior to the initiation of gametogenesis. Notably, we identify a common pre-pubertal progenitor for Leydig and myoid cells and delineate candidate factors controlling pubertal differentiation. Furthermore, pre-pubertal Sertoli cells exhibit two distinct transcriptional states differing in metabolic profiles before converging to an alternative single mature population during puberty. Roles for testosterone in Sertoli cell maturation, antimicrobial peptide secretion, and spermatogonial differentiation are further highlighted through single-cell analysis of testosterone-suppressed transfemale testes. Taken together, our transcriptional atlas of the developing human testis provides multiple insights into developmental changes and key factors accompanying male puberty.
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•A transcriptional single-cell atlas of the developing testes during human puberty•Distinctive phases of germ cell differentiation occur during puberty•Identification of a common progenitor for Leydig and myoid cells prior to puberty•Partial reversal of Sertoli and germ cell maturation upon testosterone suppression
Guo et al. provide a transcriptional cell atlas of the developing human testis during puberty, revealing dramatic developmental changes in both germ and somatic niche cell lineages. Furthermore, germ cells and Sertoli cells from testosterone-suppressed transfemale testes display partial developmental reversal, revealing critical roles for testosterone in maintaining testis maturation.
Human adult spermatogonial stem cells (hSSCs) must balance self-renewal and differentiation. To understand how this is achieved, we profiled DNA methylation and open chromatin (ATAC-seq) in SSEA4+ ...hSSCs, analyzed bulk and single-cell RNA transcriptomes (RNA-seq) in SSEA4+ hSSCs and differentiating c-KIT+ spermatogonia, and performed validation studies via immunofluorescence. First, DNA hypomethylation at embryonic developmental genes supports their epigenetic “poising” in hSSCs for future/embryonic expression, while core pluripotency genes (OCT4 and NANOG) were transcriptionally and epigenetically repressed. Interestingly, open chromatin in hSSCs was strikingly enriched in binding sites for pioneer factors (NFYA/B, DMRT1, and hormone receptors). Remarkably, single-cell RNA-seq clustering analysis identified four cellular/developmental states during hSSC differentiation, involving major transitions in cell-cycle and transcriptional regulators, splicing and signaling factors, and glucose/mitochondria regulators. Overall, our results outline the dynamic chromatin/transcription landscape operating in hSSCs and identify crucial molecular pathways that accompany the transition from quiescence to proliferation and differentiation.
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•Open chromatin in hSSCs correlates with pioneer factors and hormone receptors•hSSC differentiation involves four sequential cellular/developmental states•Key transitions involve the cell cycle, transcription factors, signaling, and metabolism
Cairns and colleagues show that human spermatogonial stem cells (hSSCs) bear unique DNA methylation and open chromatin landscapes, which may enable proper development, niche responsiveness, and “poised” pluripotency. Interestingly, single-cell transcriptome and immunofluorescence analyses reveal four cellular states, spanning from quiescent hSSCs to proliferating, metabolically active, differentiating spermatogonia.
Advances in molecular profiling have opened up the possibility to map the expression of genes in cells, tissues, and organs in the human body. Here, we combined single-cell transcriptomics analysis ...with spatial antibody-based protein profiling to create a high-resolution single-cell type map of human tissues. An open access atlas has been launched to allow researchers to explore the expression of human protein-coding genes in 192 individual cell type clusters. An expression specificity classification was performed to determine the number of genes elevated in each cell type, allowing comparisons with bulk transcriptomics data. The analysis highlights distinct expression clusters corresponding to cell types sharing similar functions, both within the same organs and between organs.
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