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Specific cell populations may have unique contributions to schizophrenia but may be missed in studies of homogenate tissue. Here laser capture microdissection followed by RNA sequencing (LCM-seq) was used to transcriptomically profile the granule cell layer of the dentate gyrus (DG-GCL) in human hippocampus and contrast these data to those obtained from bulk hippocampal homogenate. We identified widespread cell-type-enriched aging and genetic effects in the DG-GCL that were either absent or directionally discordant in bulk hippocampus data. Of the ~9 million expression quantitative trait loci identified in the DG-GCL, 15% were not detected in bulk hippocampus, including 15 schizophrenia risk variants. We created transcriptome-wide association study genetic weights from the DG-GCL, which identified many schizophrenia-associated genetic signals not found in transcriptome-wide association studies from bulk hippocampus, including GRM3 and CACNA1C. These results highlight the improved biological resolution provided by targeted sampling strategies like LCM and complement homogenate and single-nucleus approaches in human brain.
This article was published in the following journal.
Name: Nature neuroscience
On the basis of the evidence that rapid intracellular Zn dysregulation by amyloid β (Aβ) in the normal hippocampus transiently induces cognitive decline, here we report preferential neurodegeneratio...
Hypotheses about the functional properties of the dentate gyrus and adult dentate neurogenesis have been shaped by early observations of the anatomy of this region, mostly in rodents. This has led to ...
Extensive preclinical research has been conducted in recent years to reveal the cell types, neuronal circuits, molecular and morphological changes implicated in the function of the dentate gyrus in de...
In the adult brain, new dentate granule cells integrate into neural circuits and participate in hippocampal functioning. However, when and how they initiate this integration remain poorly understood....
Earlier observations in neuroscience suggested that no new neurons form in the mature central nervous system. Evidence now indicates that new neurons do form in the adult mammalian brain. Two regions ...
This project investigates the effect of ACE-inhibition on cellular metabolism by gene expression profiling of human muscle tissue, obtained by biopsy prior to and after ramipril intake. ...
To analyze the genome pattern in human gastric Intestinal Metaplasia Mucosa and duodenal Mucosa.
Current concepts of the causes of periodontitis implicate a bacterial infection as the primary cause of the disease. Several bacterial species residing in a biofilm on tooth surfaces are c...
RATIONALE: Certain drugs, such as doxycycline and voriconazole, may cause phototoxicity when a patient is exposed to ultraviolet (UV) radiation (sunlight). Studying the pattern of gene exp...
RATIONALE: Studying the genes expressed in samples of tissue from patients with cancer may help doctors identify biomarkers related to cancer. PURPOSE: This laboratory study is using gene...
Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the HIPPOCAMPUS in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose AXONS pass through the polymorphic layer ending on the DENDRITES of pyramidal cells in the hippocampus.
Axons of certain cells in the DENTATE GYRUS. They project to the polymorphic layer of the dentate gyrus and to the proximal dendrites of PYRAMIDAL CELLS of the HIPPOCAMPUS. These mossy fibers should not be confused with mossy fibers that are cerebellar afferents (see NERVE FIBERS).
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
One of four subsections of the hippocampus described by Lorente de No, located furthest from the DENTATE GYRUS.
The process that reverts CELL NUCLEI of fully differentiated somatic cells to a pluripotent or totipotent state. This process can be achieved to a certain extent by NUCLEAR TRANSFER TECHNIQUES, such as fusing somatic cell nuclei with enucleated pluripotent embryonic stem cells or enucleated totipotent oocytes. GENE EXPRESSION PROFILING of the fused hybrid cells is used to determine the degree of reprogramming. Dramatic results of nuclear reprogramming include the generation of cloned mammals, such as Dolly the sheep in 1997.
The process of gene expression is used by eukaryotes, prokaryotes, and viruses to generate the macromolecular machinery for life. Steps in the gene expression process may be modulated, including the transcription, RNA splicing, translation, and post-tran...