An atlas of human gene expression from massively parallel signature sequencing (MPSS)

Abstract

We have used massively parallel signature sequencing (MPSS) to sample the transcriptomes of 32 normal human tissues to an unprecedented depth, thus documenting the patterns of expression of almost 20,000 genes with high sensitivity and specificity. The data confirm the widely held belief that differences in gene expression between cell and tissue types are largely determined by transcripts derived from a limited number of tissue-specific genes, rather than by combinations of more promiscuously expressed genes. Expression of a little more than half of all known human genes seems to account for both the common requirements and the specific functions of the tissues sampled. A classification of tissues based on patterns of gene expression largely reproduces classifications based on anatomical and biochemical properties. The unbiased sampling of the human transcriptome achieved by MPSS supports the idea that most human genes have been mapped, if not functionally characterized. This data set should prove useful for the identification of tissue-specific genes, for the study of global changes induced by pathological conditions, and for the definition of a minimal set of genes necessary for basic cell maintenance. The data are available on the Web at http://mpss.licr.org and http://sgb.lynxgen.com.

Figure 1.

Distribution of transcript abundance classes in various tissues. For each tissue, the proportion of the transcriptome contributed by the n most abundant transcripts (abscissa) was plotted. The plots of five tissues representing extreme cases were colored: pancreas, salivary gland, and stomach as examples of highly specialized tissues with a secretory function; fetal brain and testis as examples of tissues with complex and diversified transcriptomes.

Figure 2.

Frequency histogram of gene expression. For each of the genes, the tissues showing expression at 5 tpm or more were counted. The CNS samples were averaged and counted as a single tissue.

Figure 3.

Multidimensional separation plot of the distance between gene expression patterns in the 32 tissues. The values of the pairwise correlations between expression vectors, r, were calculated from the natural logarithms of the expression values, and the distance measure d = (1 - r) was used as input for the MDS routine in the multivariate analysis package of R. The CNS tissues are red. Tissues are (AG) adrenal gland; (Bl) bladder; (BM) bone marrow; (Am) amygdala; (CN) caudate nucleus; (Ce) cerebellum; (CC) corpus callosum; (FB) fetal brain; (Hy) hypothalamus; (Ta) thalamus; (He) heart; (Ki) kidney; (Lu) lung; (MG) mammary gland; (Pn) pancreas; (PG) pituitary gland; (Pc) placenta; (Pr) prostate; (Re) retina; (SG) salivary gland; (SI) small intestine; (SC) spinal cord; (Sp) spleen; (St) stomach; (Te) testis; (Ts) thymus; (Td) thyroid; (Tr) trachea; (Ut) uterus; (Co) colon; (MC) monocytes; (PL) peripheral blood lymphocytes.

Figure 4.

Hierarchical clustering of tissues based on their pairwise distances (d = 1 - r), using the Ward statistical method. Groups of clustered tissues are colored according to common properties: (magenta) lymphoid tissues; (red) hematopoietic tissues; (green) intestinal tract; (blue) central nervous system.