The pigment cell-specific proteomeThe pigment cell transcriptomeMelanocytesRetinal pigment epithelial cellsPigment cell functionBackgroundRelevant links and publications

Tissues with pigment cellsSkinRetina

Single cell type methods

The pigment cell-specific proteome

Transcriptome analysis shows that 67% (n=13603) of all human proteins (n=20162) are detected in pigment cells and 379 of these genes show an elevated expression in any pigment cells compared to other cell type groups. In-depth analysis of the elevated genes in pigment cells using scRNA-seq and antibody-based protein profiling allowed us to visualize the expression patterns of these proteins in skin melanocytes and retinal pigment epithelial cells.

The pigment cell transcriptome

The scRNA-seq-based pigment cell transcriptome can be analyzed with regard to specificity, illustrating the number of genes with elevated expression in each specific pigment cell type compared to other cell types (Table 1). Genes with an elevated expression are divided into three subcategories:

• Cell type enriched: At least four-fold higher mRNA level in a certain cell type compared to any other cell type.
• Group enriched: At least four-fold higher average mRNA level in a group of 2-5 cell type groups (out of 53) or 2-15 cell types (out of 154) compared to any other.
• Cell type enhanced: At least four-fold higher mRNA level in a certain cell type compared to the average level in all other cell types.

Table 1. Number of genes in the subdivided specificity categories of elevated expression in pigment cells as a group compared to other grouped cell types.

Expression profiles are compared across the 154 cell types, in addition to the comparison across the 53 grouped cell types. This results in cell specificity categories based on two datasets, one more detailed across all cell types and one more suitable for the general overview based on the grouped cell types with similar expression profile and functions. Cell types are grouped based on function and biology, to facilitate a better overview and to complement the detailed information based on all cell types.

Table 2. Number of genes in the subdivided specificity categories of elevated expression in the pigment cell types compared to all other cell types.

Melanocytes

Melanocytes are mainly located in the basal layer of the epidermis and their primary role is to produce and deliver melanin-pigment to keratinocytes through dendritic processes. As shown in Table 2, 248 genes show elevated expression in melanocytes compared to other cell types. Genes with elevated expression in melanocytes include MLANA and DCT, which encode proteins involved in the melanin-synthesis pathways.

MLANA - skin
MLANA - skin
MLANA - skin

DCT - skin
DCT - skin
DCT - skin

Retinal pigment epithelial cells

Retinal pigment epithelial (RPE) cells form a single layer of pigmented cells located between the retina’s photoreceptors and the choroid. Their main functions include nourishing and supporting photoreceptors, absorbing excess light to reduce scattering, phagocytosing shed photoreceptor outer segments, and maintaining the blood-retina barrier. They also play key roles in retinoid recycling for visual pigment regeneration and in ion and fluid transport to keep the retinal environment stable. As shown in Table 2, 457 genes show elevated expression in retinal pigment epithelial cells compared to other cell types. The proteins bestrophin 1 (BEST1) and solute carrier family 16 member 8 (SLC16A8) both play a role in the transport of molecules and have elevated expression in the retina.

BEST1 - eye
BEST1 - eye
BEST1 - retina

SLC16A8 - eye
SLC16A8 - eye
SLC16A8 - retina

Pigment cell function

The two pigment cell types are melanocytes and retinal pigment cells. Melanocytes originate from neural crest cells, while retina pigment cells originate from the optic neuroepithelium. The main objective of melanocytes is to produce melanin, which protects the skin against UV-radiation. It is melanin produced by melanocytes in the uveal part of the eye that gives eyes their color. When melanin is exposed to UV-radiation from the sun, it becomes darker to protect the skin from further damage to the tissue. The amount of melanin produced by the melanocytes differs between individuals but the amount of melanocytes is the same. Lack of melanin production can lead to a disease called albinism, where the individual has no pigmentation at all and it will affect both eye and hair pigmentation. Moreover, melanocytes have immune cell qualities such as phagocytosis, antigen presentation capabilities and cytokine production.

Retinal pigment cells form retinal pigment epithelium in the back of the eye, adjacent to the retina. The retinal pigment epithelium works as a retinal-blood barrier and protects the retina. Similarly to melanocytes, retinal pigment cells produce pigment, however instead of protecting the skin, retinal pigment cells protect the retina from UV-radiation. Retinal pigment cells are in constant connection with the photoreceptor cells of the retina and support these cells in various ways. They buffer ions and water between photoreceptor cells and blood. Pigment cells also store 11-cis-retinal, a molecule essential for the transformation of light into visual signals in photoreceptor cells. They can quickly supply photoreceptor cells with 11-cis-retinal, when this molecule is depleted in photoreceptor cells.

The histology of organs that contain pigment cells, including interactive images, is described in the Protein Atlas Histology Dictionary.

Background

Here, the protein-coding genes expressed in pigment cells are described and characterized, together with examples of immunohistochemically stained tissue sections that visualize corresponding protein expression patterns of genes with elevated expression in different pigment cell types.

The transcript profiling was based on publicly available genome-wide expression data from scRNA-seq and snRNA-seq experiments (36 datasets) covering 34 tissues. All datasets (unfiltered read counts of cells) were clustered independenty using leiden clustering, resulting in a total of 1175 different cell type clusters. The clusters were then manually annotated based on a survey of known tissue and cell type-specific markers. The RNA-seq data from each cluster of cells was aggregated to mean normalized protein-coding counts per million (nCPM) for all protein-coding genes. A specificity and distribution classification was performed for both single cell types individually, as well as grouped into 53 main cell type groups. The specificity classification determined the number of elevated genes, while the distribution determined whether genes are detected in one, several or all cell types or cell type groups.

It should be noted that since the analysis was limited to datasets representing 34 tissue types, not all human cell types are represented. Furthermore, some cell types are present only in low amounts, or identified only in mixed cell clusters, which may affect the results and bias the cell type specificity.

Relevant links and publications

Uhlén M et al., Tissue-based map of the human proteome. Science (2015)
PubMed: 25613900 DOI: 10.1126/science.1260419

Fagerberg L et al., Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol Cell Proteomics. (2014)
PubMed: 24309898 DOI: 10.1074/mcp.M113.035600

Solé-Boldo L et al., Single-cell transcriptomes of the human skin reveal age-related loss of fibroblast priming. Commun Biol. (2020)
PubMed: 32327715 DOI: 10.1038/s42003-020-0922-4