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Defining cell populations with single-cell gene expression profiling: correlations and identification of astrocyte subpopulations.

Journal article
Authors Anders Ståhlberg
Daniel Andersson
Johan Aurelius
Maryam Faiz
Marcela Pekna
Mikael Kubista
Milos Pekny
Published in Nucleic acids research
Volume 39
Issue 4
Pages e24
ISSN 1362-4962
Publication year 2011
Published at Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation
Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Institute of Biomedicine, Department of Infectious Medicine
Pages e24
Language en
Links dx.doi.org/10.1093/nar/gkq1182
Keywords Animals, Astrocytes, classification, metabolism, Cells, Cultured, Gene Expression, Gene Expression Profiling, methods, Mice, RNA, Messenger, analysis, Single-Cell Analysis, Stem Cells, metabolism, Up-Regulation
Subject categories Medical and Health Sciences

Abstract

Single-cell gene expression levels show substantial variations among cells in seemingly homogenous populations. Astrocytes perform many control and regulatory functions in the central nervous system. In contrast to neurons, we have limited knowledge about functional diversity of astrocytes and its molecular basis. To study astrocyte heterogeneity and stem/progenitor cell properties of astrocytes, we used single-cell gene expression profiling in primary mouse astrocytes and dissociated mouse neurosphere cells. The transcript number variability for astrocytes showed lognormal features and revealed that cells in primary cultures to a large extent co-express markers of astrocytes and neural stem/progenitor cells. We show how subpopulations of cells can be identified at single-cell level using unsupervised algorithms and that gene correlations can be used to identify differences in activity of important transcriptional pathways. We identified two subpopulations of astrocytes with distinct gene expression profiles. One had an expression profile very similar to that of neurosphere cells, whereas the other showed characteristics of activated astrocytes in vivo.

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