Dataset Information

Cell-type and brain-region resolved mouse brain proteome

ABSTRACT: To understand the complexity of the brain, connectome and transcriptome maps of high resolution are being generated, but an equivalent catalogue of the brain proteome is lacking. To provide a starting point, we have performed an in-depth proteome analysis of the adult mouse brain, its major regions and cell types, which resulted in the so far largest collection of cell-type resolved protein expression data of the brain. Comparisons of the 12,934 identified proteins in oligodendrocytes, astrocytes, microglia and cortical neurons with deep sequencing data of the transcriptome indicated deep coverage of the proteome. We identified novel protein makers for different cell type and brain regions. These were validated either directly such as in case of cell types or by comparative analysis against Allen mouse brain atlas. The utility and the power of the resource were demonstrated by the identification of Lsamp, an adhesion molecule of the IgLON family, as a negative regulator of myelination in a subpopulation of neurons. Our in-depth proteome analysis of CNS cell types provides a framework towards a system-level understanding of cell type diversity in the CNS and serves as a rich resource to the neuroscience community for the better understanding of brain development and function.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Prof. Dr. Matthias Mann

PROVIDER: MSV000084941 | MassIVE | Sat Feb 08 11:13:00 GMT 2020

SECONDARY ACCESSION(S): PXD001250

REPOSITORIES: MassIVE

ACCESS DATA

Publications

Cell type- and brain region-resolved mouse brain proteome.

Sharma Kirti K Schmitt Sebastian S Bergner Caroline G CG Tyanova Stefka S Kannaiyan Nirmal N Manrique-Hoyos Natalia N Kongi Karina K Cantuti Ludovico L Hanisch Uwe-Karsten UK Philips Mari-Anne MA Rossner Moritz J MJ Mann Matthias M Simons Mikael M

Nature neuroscience 20151102 12

Brain transcriptome and connectome maps are being generated, but an equivalent effort on the proteome is currently lacking. We performed high-resolution mass spectrometry-based proteomics for in-depth analysis of the mouse brain and its major brain regions and cell types. Comparisons of the 12,934 identified proteins in oligodendrocytes, astrocytes, microglia and cortical neurons with deep sequencing data of the transcriptome indicated deep coverage of the proteome. Cell type-specific proteins d ...[more]

PMID: 26523646

Similar Datasets

Project description:A Transcriptome Database for Astrocytes, Neurons, and Oligodendrocytes: A New Resource for Understanding Brain Development and Function Understanding the cell-cell interactions that control CNS development and function has long been limited by the lack of methods to cleanly separate astrocytes, neurons, and oligodendrocytes. Here we describe the first method for the isolation and purification of developing and mature astrocytes from mouse forebrain. This method takes advantage of the expression of S100β by astrocytes. We used fluorescent activated cell sorting (FACS) to isolate EGFP positive cells from transgenic mice that express EGFP under the control of an S100β promoter. By depletion of astrocytes and oligodendrocytes we obtained purified populations of neurons, while by panning with oligodendrocyte-specific antibodies we obtained purified populations of oligodendrocytes. Using GeneChip Arrays we then created a transcriptome database of the expression levels of over 20,000 genes by gene profiling these three main CNS neural cell types at postnatal ages day 1 to 30. This database provides the first global characterization of the genes expressed by mammalian astrocytes in vivo and is the first direct comparison between the astrocyte, neuron, and oligodendrocyte transcriptomes. We demonstrate that Aldh1L1, a highly expressed astrocyte gene, is a highly specific antigenic marker for astrocytes with a substantially broader, and therefore potentially more useful, pattern of astrocyte expression than the traditional astrocyte marker GFAP. This transcriptome database of acutely isolated and highly pure populations of astrocytes, neurons and oligodendrocytes provides a resource to the neuroscience community by providing improved cell type specific markers and for better understanding of neural development, function, and disease. We acutely purified mouse astrocytes from early postnatal ages (P1) to later postnatal ages (P30), when astrocyte differentiation is morphologically complete (Bushong et al., 2004), and acutely purified mouse OL-lineage cells from stages ranging from OPCs to newly differentiated OLs to myelinating OLs. We extracted RNA from each of these highly purified, acutely isolated cell types and used GeneChip Arrays to determine the expression levels of over 20,000 genes and construct a comprehensive database of cell type specific gene expression in the mouse forebrain. Analysis of this database confirms cell type specific expression of many well characterized and functionally important genes. In addition, we have identified thousands of new cell type enriched genes, thereby providing important new information about astrocyte, OL, and neuron interactions, metabolism, development, and function. This database provides a comparison of the genome-wide transcriptional profiles of the main CNS cell types and is a resource to the neuroscience community for better understanding the development, physiology, and pathology of the CNS. Keywords: Developmental CNS Cell type comparision

Dataset Information

Cell-type and brain-region resolved mouse brain proteome

Publications

Cell type- and brain region-resolved mouse brain proteome.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure