THE HUMAN TISSUE PROTEOMES

Extended brain samples



The Tissue atlas is based on immunohistochemical staining of tissue microarrays from 44 different normal tissue types. In addition to the standard setup, extended tissue profiling is performed for selected proteins, to give a more complete overview on where the protein is expressed. Extended tissue samples include mouse brain, human lactating breast, eye, hair and additional samples of adrenal gland, skin and brain. For extended brain samples, both tissue microarrays with 1 mm diameter cores and tissue section samples are used.

The full list of proteins analyzed in extended brain samples is found in Table 1.


Hypothalamus


The hypothalamus, a part of the diencephalon (interbrain), is located below the thalamus and above the pituitary gland. The hypothalamus is considered to be the link between the nervous and endocrine system, and plays an essential role in metabolism and homeostasis – by regulating the autonomic nervous system, production of hormones (via the pituitary gland), and controlling body temperature. The hypothalamus is also involved in regulation of behavior, food intake and circadian rhythm. The hypothalamus can be divided into three different regions based on structure and function; the anterior, tuberal and posterior regios, which further can be structured into several nuclei and areas. Extended protein profiling in human hypothalamus was performed using large tissue sections (20 x 30 mm). Only images representing regions of interest are selected for inclusion on the Human Protein Atlas.

The pro-melanin concentrating hormone (PMCH) encodes a preproprotein, and is proteolytically processed to generate multiple proteins. PMCH is mainly expressed in a subset of hypothalamic neurons (Figure 1).

Figure 1. Immunohistochemical staining of human hypothalamus using an antibody towards PMCH shows strong cytoplasmic staining in neuronal cells.


Hippocampal formation


Located in the medial temporal lobes, surrounded by the entorhinal, parahippocampal and perirhinal cortices, lies the hippocampus. The hippocampus belongs to the limbic system. The dorsal part is involved in episodic memory and spatial navigation, while the ventral hippocampus is implicated in emotion-related connections. The hippocampus is included in the standard tissue microarray setup. Extended protein profiling of human hippocampus, using a tissue section (20 x 30 mm) which includes the dentate gyrus/hippocampal cornus ammonis (CA) areas, was performed in order to give a wider perspective of the protein localization and assess protein expression in cells that are not included in the standard setup due to tissue sampling. Only images representing regions of interest are selected for inclusion on the Human Protein Atlas.


Cerebral cortex


The cerebral cortex (also known as the neocortex) is a complex, multilayered (six layers), highly organized structure, and the outer layer of the brain in humans and most mammals. The cerebral cortex contains a high number of different neuronal and glial cells types. The cortical neurons comprise mainly of two classes: the interneurons and the pyramidal (projection) neurons, which can further be classified based on morphological and molecular signatures. The cerebral cortex is included in the standard tissue microarray setup. Extended protein profiling using a tissue section (15 x 20 mm) from the human cerebral cortex frontal lobe was performed in order to give a wider perspective of the protein localization and assess protein expression in cells that are not included in the standard setup due to tissue sampling.


Pituitary gland


The pituitary gland (also called hypophysis) consists of two glands, the anterior (adeno) pituitary gland, and the posterior (neuro) pituitary gland. The anterior pituitary gland is divided into three regions: pars distalis, pars tuberalis and pars intermedia. These structures consist mainly of hormone-producing epithelial cells that store hormones in secretory granules, to later be released in the blood stream. The hormones act on various tissues. One example is the peptide hormone prolactin (PRL) that stimulates the mammary glands to produce milk. Prolactin is expressed in the anterior pituitary gland (Figure 2). The posterior pituitary gland consists mainly of unmyelinated axons of secretory neuronal cells located in the supraoptic and periventricular nuclei of the hypothalamus. The neurons produce a neurosecretory material, containing antidiuretic hormones and oxytocin, which travels along the axons from the hypothalamic neurons to the nerve endings in the posterior pituitary, specifically to the pars nervosa - the main structure of the posterior gland. Extended protein profiling in human pituitary gland was performed using a tissue microarray with 1 mm diameter cores.

Figure 2. Immunohistochemical staining of human pituitary gland towards PRL shows strong cytoplasmic positivity in endocrine cells.


Table 1. The following 40 genes have been analyzed using extended brain samples.

Gene

Gene description

Tissue

Staining pattern

ARHGAP36 Rho GTPase activating protein 36 Pituitary gland Strong cytoplasmic staining in a subset of cells in anterior pituitary gland.
CGA Glycoprotein hormones, alpha polypeptide Pituitary gland Anterior lobe of pituitary gland strongly stained.
CHST14 Carbohydrate (N-acetylgalactosamine 4-0) sulfotransferase 14 Pituitary gland Strong cytoplasmic staining in subsets of cells in anterior pituitary.
CSH1 Chorionic somatomammotropin hormone 1 (placental lactogen) Pituitary gland Strong cytoplasmic positivity in pituitary gland.
CSH2 Chorionic somatomammotropin hormone 2 Pituitary gland Strong cytoplasmic positivity in pituitary gland.
CSHL1 Chorionic somatomammotropin hormone-like 1 Pituitary gland Strong cytoplasmic positivity in pituitary gland.
DDX25 DEAD (Asp-Glu-Ala-Asp) box helicase 25 Cerebral cortex Strong cytoplasmic staining in subsets of astrocyte-like cells and neuronal cells.
DDX25 DEAD (Asp-Glu-Ala-Asp) box helicase 25 Hypothalamus Strong staining processes and in subsets of astrocyte-like cells.
EGR4 Early growth response 4 Cerebral cortex Strong cytoplasmic and nuclear positivity in subsets of neuronal cells with moderate positivity in a rare number of glial cells.
FEZF1 FEZ family zinc finger 1 Hypothalamus Distinct positivity in processes and neuropil of hypothalamus.
FSHB Follicle stimulating hormone, beta polypeptide Pituitary gland Strong cytoplasmic staining in a subset of cells in anterior pituitary gland.
GAL Galanin/GMAP prepropeptide Pituitary gland Subsets of cells in anterior pituitary show strong cytoplasmic staining.
GH1 Growth hormone 1 Pituitary gland Strong cytoplasmic positivity in pituitary gland.
GH2 Growth hormone 2 Pituitary gland Strong cytoplasmic positivity in pituitary gland.
GNRH1 Gonadotropin-releasing hormone 1 (luteinizing-releasing hormone) Hypothalamus Strong cytoplasmic staining in a subset of hypothalamic neuronal cells.
GNRHR Gonadotropin-releasing hormone receptor Pituitary gland Moderate cytoplasmic staining in anterior pituitary gland.
GPR26 G protein-coupled receptor 26 Cerebral cortex Strong cytoplasmic staining in a subset of glial cells.
GPR50 G protein-coupled receptor 50 Pituitary gland Strong cytoplasmic staining in anterior and posterior pituitary gland.
IGSF1 Immunoglobulin superfamily, member 1 Pituitary gland Strong membranous staining in cells in anterior pituitary gland.
KCNG2 Potassium channel, voltage gated modifier subfamily G, member 2 Hippocampus Distinct astrocyte end-feet staining in hippocampus.
LHB Luteinizing hormone beta polypeptide Pituitary gland Strong cytoplasmic staining in cells of the anterior pituitary.
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