A compendium of gene expression in normal human tissues

This study creates a compendium of gene expression in normal human tissues suitable as a reference for defining basic organ systems biology. Using oligonucleotide microarrays, we analyze 59 samples representing 19 distinct tissue types. Of ∼7,000 genes analyzed, 451 genes are expressed in all tissue types and designated as housekeeping genes. These genes display significant variation in expression levels among tissues and are sufficient for discerning tissue-specific expression signatures, indicative of fundamental differences in biochemical processes. In addition, subsets of tissue-selective genes are identified that define key biological processes characterizing each organ. This compendium highlights similarities and differences among organ systems and different individuals and also provides a publicly available resource (Human Gene Expression Index, the HuGE Index, http://www.hugeindex.org ) for future studies of pathophysiology.

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Mapping cis-regulatory elements in the midgestation mouse placenta

Scientific Reports ◽

10.1038/s41598-021-01664-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Rebekah R. Starks ◽

Haninder Kaur ◽

Geetu Tuteja

Keyword(s):

Gene Expression ◽

Neuronal Development ◽

Housekeeping Genes ◽

Regulatory Elements ◽

Large Network ◽

Motif Analysis ◽

Placental Development ◽

Specific Expression ◽

Future Studies ◽

Mouse Placenta

AbstractThe placenta is a temporary organ that provides the developing fetus with nutrients, oxygen, and protection in utero. Defects in its development, which may be caused by misregulated gene expression, can lead to devastating outcomes for the mother and fetus. In mouse, placental defects during midgestation commonly lead to embryonic lethality. However, the regulatory mechanisms controlling expression of genes during this period have not been thoroughly investigated. Therefore, we generated and analyzed ChIP-seq data for multiple histone modifications known to mark cis-regulatory regions. We annotated active and poised promoters and enhancers, as well as regions generally associated with repressed gene expression. We found that poised promoters were associated with neuronal development genes, while active promoters were largely associated with housekeeping genes. Active and poised enhancers were associated with placental development genes, though only active enhancers were associated with genes that have placenta-specific expression. Motif analysis within active enhancers identified a large network of transcription factors, including those that have not been previously studied in the placenta and are candidates for future studies. The data generated and genomic regions annotated provide researchers with a foundation for future studies, aimed at understanding how specific genes in the midgestation mouse placenta are regulated.

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Massively parallel in vivo CRISPR screening identifies RNF20/40 as epigenetic regulators of cardiomyocyte maturation

Nature Communications ◽

10.1038/s41467-021-24743-z ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Nathan J. VanDusen ◽

Julianna Y. Lee ◽

Weiliang Gu ◽

Catalina E. Butler ◽

Isha Sethi ◽

...

Keyword(s):

Gene Expression ◽

Genetic Screen ◽

Forward Genetics ◽

Epigenetic Mark ◽

Biological Processes ◽

Dynamic Changes ◽

Forward Genetic Screen ◽

High Resource ◽

Organ Systems

AbstractThe forward genetic screen is a powerful, unbiased method to gain insights into biological processes, yet this approach has infrequently been used in vivo in mammals because of high resource demands. Here, we use in vivo somatic Cas9 mutagenesis to perform an in vivo forward genetic screen in mice to identify regulators of cardiomyocyte (CM) maturation, the coordinated changes in phenotype and gene expression that occur in neonatal CMs. We discover and validate a number of transcriptional regulators of this process. Among these are RNF20 and RNF40, which form a complex that monoubiquitinates H2B on lysine 120. Mechanistic studies indicate that this epigenetic mark controls dynamic changes in gene expression required for CM maturation. These insights into CM maturation will inform efforts in cardiac regenerative medicine. More broadly, our approach will enable unbiased forward genetics across mammalian organ systems.

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Development of cDNA normalization system and preliminary transcription analysis of KCS genes in apple tissues

Acta Universitatis Agriculturae et Silviculturae Mendelianae Brunensis ◽

10.11118/actaun201159030009 ◽

2011 ◽

Vol 59 (3) ◽

pp. 9-12 ◽

Cited By ~ 3

Author(s):

Zsolt Albert ◽

Cs. Deák ◽

A. Miskó ◽

M. Tóth ◽

I. Papp

Keyword(s):

Gene Expression ◽

Expression System ◽

Expression Patterns ◽

Housekeeping Genes ◽

Apple Fruit ◽

Rt Pcr ◽

Specific Primers ◽

Specific Expression ◽

Transcription Analysis ◽

Tissue Specific

Wax production is an important aspect of apple (Malus domestica Borkh.) fruit development from both theoretical and practical point of views. The complex molecular mechanism that controls wax biosynthesis is still widely unknown but many studies focused on this topic. We aimed to develop further the experimental framework of these efforts with a description of an improved reference genes expression system. Results in the literature show that similarities exist among the expression of some housekeeping genes of different plant species. Based on these considerations and on gene expression data from Arabidopsis thaliana, some genes in apple were assigned for analysis. EST sequences of apple were used to design specific primers for RT-PCR experiments. Isolation of intact RNA from different apple tissues and performing RT-PCR reaction were also key point in obtaining expression patterns. To monitor DNA contamination of the RNA samples, specific primers were used that amplify intron-containing sequences from the cDNA. We found that actin primers can be used for the detection of intron containing genomic DNA, and tubulin primers are good internal controls in RT-PCR experiments. We were able to make a difference between tissue-specific and tissue-independent gene-expression, furthermore we found tissue specific differences between the expression patterns of candidate genes, that are potentially involved in wax-biosynthesis. Our results show that KCS1 and KCS4 are overexpressed in the skin tissue, this could mean that these genes have skin-specific expression in apple fruit.

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Uroplakin gene expression in normal human tissues and locally advanced bladder cancer

The Journal of Pathology ◽

10.1002/path.1252 ◽

2002 ◽

Vol 199 (1) ◽

pp. 41-49 ◽

Cited By ~ 91

Author(s):

Jonathon Olsburgh ◽

Patricia Harnden ◽

Robert Weeks ◽

Barbara Smith ◽

Adrian Joyce ◽

...

Keyword(s):

Gene Expression ◽

Bladder Cancer ◽

Locally Advanced ◽

Human Tissues ◽

Advanced Bladder Cancer ◽

Normal Human

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Identifying core biological processes distinguishing human eye tissues with precise systems-level gene expression analyses and weighted correlation networks

10.1101/136960 ◽

2017 ◽

Author(s):

John M Bryan ◽

Temesgen D Fufa ◽

Kapil Bharti ◽

Brian P Brooks ◽

Robert B Hufnagel ◽

...

Keyword(s):

Gene Expression ◽

Expression Patterns ◽

Mouse Retina ◽

Human Tissues ◽

Biological Processes ◽

Rna Seq ◽

Human Eye ◽

Correlation Networks ◽

Eye Tissues ◽

Study Gene Expression

AbstractThe human eye is built from several specialized tissues which direct, capture, and pre-process information to provide vision. The gene expression of the different eye tissues has been extensively profiled with RNA-seq across numerous studies. Large consortium projects have also used RNA-seq to study gene expression patterning across many different human tissues, minus the eye. There has not been an integrated study of expression patterns from multiple eye tissues compared to other human body tissues. We have collated all publicly available healthy human eye RNA-seq datasets as well as dozens of other tissues. We use this fully integrated dataset to probe the biological processes and pan expression relationships between the cornea, retina, RPE-choroid complex, and the rest of the human tissues with differential expression, clustering, and GO term enrichment tools. We also leverage our large collection of retina and RPE-choroid tissues to build the first human weighted gene correlation networks and use them to highlight known biological pathways and eye gene disease enrichment. We also have integrated publicly available single cell RNA-seq data from mouse retina into our framework for validation and discovery. Finally, we make all these data, analyses, and visualizations available via a powerful interactive web application (https://eyeintegration.nei.nih.gov/).

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THE STUDY OF ORTHOPEDIA HOMEOBOX GENE EXPRESSION IN DIFFERENT TUMOR AND NORMAL HUMAN TISSUES

Problems in oncology ◽

10.37469/0507-3758-2017-63-1-128-134 ◽

2017 ◽

Vol 63 (1) ◽

pp. 128-134

Author(s):

Yuliya Karnaukhova ◽

Dmitriy Polev ◽

Larisa Krukovskaya ◽

Andrey Kozlov

Keyword(s):

Gene Expression ◽

Homeobox Gene ◽

Cancer Diagnostics ◽

Human Tissues ◽

Embryonic Tissues ◽

Dna Strands ◽

Normal Human ◽

Testis Tissue ◽

Gene Mrna ◽

Cancer Testis

There was studied the OTP gene expression in different normal and tumor human tissues using PCR with specific primers. OTP gene is expressed in 23 of 29 tumor samples and intron fragment of OTP gene (sequence AI267901) is expressed in 49 of 59 tumor samples of different localization. Studied fragments of OTP gene are not transcribed in normal and embryonic tissues except for normal testis tissue, i.e. they can be classified as cancer-testis transcripts. According to preliminary data AI267901 RNA and OTP gene mRNA are transcribed from different DNA strands. Thus locus of OTP gene provides two independent tumor specific transcripts which are potential markers for the cancer diagnostics.

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CpG islands in genes showing tissue-specific expression

Philosophical Transactions of the Royal Society of London Series B Biological Sciences ◽

10.1098/rstb.1990.0005 ◽

1990 ◽

Vol 326 (1235) ◽

pp. 207-215 ◽

Cited By ~ 14

Keyword(s):

Gene Expression ◽

Cpg Islands ◽

Housekeeping Genes ◽

Tissue Expression ◽

Proximal Promoter ◽

Cell Type ◽

Promoter Regions ◽

Specific Expression ◽

Tissue Specific ◽

Single Cell Type

Patterns of DNA methylation at GpG dinucleotides and their relations with gene expression are complex. Methylation-free CpG clusters, so-called HTF islands, are most often associated with the promoter regions of housekeeping genes, whereas genes expressed in a single-cell type are usually deficient in these sequences. However, in the human carbonic anhydrase (CA) gene family, both the ubiquitously expressed CAII and the muscle specific CAIII appear to have such CpG islands although erythrocyte-specific CAI does not. The CAII island is quantitatively more CpG rich than that of CAIII, with a CpG :GpC ratio of 0.94 compared with 0.82 for CAIII. Estimation of CpG:GpC ratios in the proximal-promoter regions of 44 vertebrate genes suggest that 40% of genes with tissue-specific or limited tissue distribution may show methylation-free CpG clusters in their promoter regions. In many cases the CpG:GpC ratio is less than that found in housekeeping genes and this may reflect variation in the interaction of CpG clusters with regulatory factors that define different patterns of tissue expression.

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GAPDH as a housekeeping gene: analysis of GAPDH mRNA expression in a panel of 72 human tissues

Physiological Genomics ◽

10.1152/physiolgenomics.00025.2005 ◽

2005 ◽

Vol 21 (3) ◽

pp. 389-395 ◽

Cited By ~ 392

Author(s):

Robert D. Barber ◽

Dan W. Harmer ◽

Robert A. Coleman ◽

Brian J. Clark

Keyword(s):

Gene Expression ◽

Mrna Expression ◽

Gene Expression Data ◽

Internal Control ◽

Housekeeping Genes ◽

Housekeeping Gene ◽

Human Tissues ◽

Expression Data ◽

Expression Levels ◽

Gapdh Mrna

Quantitative gene expression data are often normalized to the expression levels of control or so-called “housekeeping” genes. An inherent assumption in the use of housekeeping genes is that expression of the genes remains constant in the cells or tissues under investigation. Although exceptions to this assumption are well documented, housekeeping genes are of value in fully characterized systems. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is one of the most commonly used housekeeping genes used in comparisons of gene expression data. To investigate the value of GAPDH as a housekeeping gene in human tissues, the expression of GAPDH mRNA was measured in a panel of 72 different pathologically normal human tissue types. Measurements were obtained from 371,088 multiplexed, quantitative real-time RT-PCRs with specific target genes. Significant differences in the expression levels of GAPDH mRNA were observed between tissue types and between donors of the same tissue. A 15-fold difference in GAPDH mRNA copy numbers was observed between the highest and lowest expressing tissue types, skeletal muscle and breast, respectively. No specific effect of either age or gender was observed on GAPDH mRNA expression. These data provide an extensive analysis of GAPDH mRNA expression in human tissues and confirm previous reports of the marked variability of GAPDH expression between tissue types. These data establish comparative levels of expression and can be used to add value to gene expression data in which GAPDH is used as the internal control.

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