The transcriptomic and proteomic landscapes of bone marrow and secondary lymphoid tissues

Abstract

Background: The sequencing of the human genome has opened doors for global gene expression profiling, and the immense amount of data will lay an important ground for future studies of normal and diseased tissues. The Human Protein Atlas project aims to systematically map the human gene and protein expression landscape in a multitude of normal healthy tissues as well as cancers, enabling the characterization of both housekeeping genes and genes that display a tissue-specific expression pattern. This article focuses on identifying and describing genes with an elevated expression in four lymphohematopoietic tissue types (bone marrow, lymph node, spleen and appendix), based on the Human Protein Atlas-strategy that combines high throughput transcriptomics with affinity-based proteomics.

Results: An enriched or enhanced expression in one or more of the lymphohematopoietic tissues, compared to other tissue-types, was seen for 693 out of 20,050 genes, and the highest levels of expression were found in bone marrow for neutrophilic and erythrocytic genes. A majority of these genes were found to constitute well-characterized genes with known functions in lymphatic or hematopoietic cells, while others are not previously studied, as exemplified by C19ORF59.

Conclusions: In this paper we present a strategy of combining next generation RNA-sequencing with in situ affinity-based proteomics in order to identify and describe new gene targets for further research on lymphatic or hematopoietic cells and tissues. The results constitute lists of genes with enriched or enhanced expression in the four lymphohematopoietic tissues, exemplified also on protein level with immunohistochemical images.

Figure 1. Dendrogram and correlation plots for the lymphohematopoietic tissues.

a) Dendrogram covering all samples of the four lymphohematopoietic tissue types visualizing clustering according to gene expression profiles. Correlation plots are shown for b) spleen and bone marrow displaying the lowest correlation between the four lymphohematopoietic tissues, and for c) lymph node and appendix displaying the highest correlation, based on the average FPKM-value of all samples within the same tissue type (n = 3–5).

Figure 2. Pie charts displaying the expression profiles for the lymphohematopoietic tissues.

The upper panel shows the percentage of genes expressed within the different categories of expression, for bone marrow and for the secondary lymphoid organs respectively. The lower panel pie charts show the percentage of transcripts (FPKM) for each category.

Figure 3. Network plot visualizing the relationship of enriched genes in the lymphohematopoietic tissues.

a) Dark blue nodes represent genes that are group enriched in up to five different tissue types including at least one of the lymphohematopoietic tissues. The light blue nodes represent the total number of highly and moderately tissue enriched genes in each lymphohematopoietic tissue. The size of each blue (dark and light) node is related to the square root of the number of genes within. Black circles represent the four lymphohematopoietic tissues, and grey circles denote other tissue types. b) Names of enriched genes (and enhanced genes in brackets) that are exemplified in the text and shown in Fig. 4. The color codes are equal to the nodes in a). The network plot is limited to include nodes with a minimum of two genes.

Figure 4. Immunohistochemical staining of protein expression.

The staining patterns of 19 proteins transcribed from genes in the enriched or enhanced categories are exemplified here in one to three tissue types. The gene name, tissue type and FPKM-value in brackets are shown for each image. BM: bone marrow; LN: lymph node; Appx: appendix.