The cell type resolved mouse transcriptome in neuron-enriched brain tissues from the hippocampus and cerebellum during prion disease

Abstract Multiple cell types and complex connection networks are an intrinsic feature of brain tissue. In this study we used expression profiling of specific microscopic regions of heterogeneous tissue sections isolated by laser capture microdissection (LCM) to determine insights into the molecular...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Anna Majer, Sarah J. Medina, Debra Sorensen, Matthew J. Martin, Kathy L. Frost, Clark Phillipson, Kathy Manguiat, Stephanie A. Booth
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a5215f0e0d6d49c7899b2cea69864fb5
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a5215f0e0d6d49c7899b2cea69864fb5
record_format	dspace
spelling	oai:doaj.org-article:a5215f0e0d6d49c7899b2cea69864fb52021-12-02T15:09:51ZThe cell type resolved mouse transcriptome in neuron-enriched brain tissues from the hippocampus and cerebellum during prion disease10.1038/s41598-018-37715-z2045-2322https://doaj.org/article/a5215f0e0d6d49c7899b2cea69864fb52019-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-37715-zhttps://doaj.org/toc/2045-2322Abstract Multiple cell types and complex connection networks are an intrinsic feature of brain tissue. In this study we used expression profiling of specific microscopic regions of heterogeneous tissue sections isolated by laser capture microdissection (LCM) to determine insights into the molecular basis of brain pathology in prion disease. Temporal profiles in two mouse models of prion disease, bovine spongiform encephalopathy (BSE) and a mouse-adapted strain of scrapie (RML) were performed in microdissected regions of the CA1 hippocampus and granular layer of the cerebellum which are both enriched in neuronal cell bodies. We noted that during clinical disease the number of activated microglia and astrocytes that occur in these areas are increased, thereby likely diluting the neuronal gene expression signature. We performed a comparative analysis with gene expression profiles determined from isolated populations of neurons, microglia and astrocytes to identify transcripts that are enriched in each of these cell types. Although the incubation periods of these two models are quite different, over 300 days for BSE and ~160 days for RML scrapie, these regional microdissections revealed broadly similar profiles. Microglial and astrocyte-enriched genes contributed a profound inflammatory profile consisting of inflammatory cytokines, genes related to phagocytosis, proteolysis and genes coding for extracellular matrix proteins. CA1 pyramidal neurons displayed a net upregulation of transcription factors and stress induced genes at pre-clinical stages of disease while all tissues showed profound decrease of overlapping genes related to neuronal function, in particular transcripts related to neuronal communication including glutamate receptors, phosphatase subunits and numerous synapse-related markers. Of note, we found a small number of genes expressed in neurons that were upregulated during clinical disease including, COX6A2, FZD9, RXRG and SOX11, that may be biomarkers of neurodegeneration.Anna MajerSarah J. MedinaDebra SorensenMatthew J. MartinKathy L. FrostClark PhillipsonKathy ManguiatStephanie A. BoothNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-14 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anna Majer Sarah J. Medina Debra Sorensen Matthew J. Martin Kathy L. Frost Clark Phillipson Kathy Manguiat Stephanie A. Booth The cell type resolved mouse transcriptome in neuron-enriched brain tissues from the hippocampus and cerebellum during prion disease
description	Abstract Multiple cell types and complex connection networks are an intrinsic feature of brain tissue. In this study we used expression profiling of specific microscopic regions of heterogeneous tissue sections isolated by laser capture microdissection (LCM) to determine insights into the molecular basis of brain pathology in prion disease. Temporal profiles in two mouse models of prion disease, bovine spongiform encephalopathy (BSE) and a mouse-adapted strain of scrapie (RML) were performed in microdissected regions of the CA1 hippocampus and granular layer of the cerebellum which are both enriched in neuronal cell bodies. We noted that during clinical disease the number of activated microglia and astrocytes that occur in these areas are increased, thereby likely diluting the neuronal gene expression signature. We performed a comparative analysis with gene expression profiles determined from isolated populations of neurons, microglia and astrocytes to identify transcripts that are enriched in each of these cell types. Although the incubation periods of these two models are quite different, over 300 days for BSE and ~160 days for RML scrapie, these regional microdissections revealed broadly similar profiles. Microglial and astrocyte-enriched genes contributed a profound inflammatory profile consisting of inflammatory cytokines, genes related to phagocytosis, proteolysis and genes coding for extracellular matrix proteins. CA1 pyramidal neurons displayed a net upregulation of transcription factors and stress induced genes at pre-clinical stages of disease while all tissues showed profound decrease of overlapping genes related to neuronal function, in particular transcripts related to neuronal communication including glutamate receptors, phosphatase subunits and numerous synapse-related markers. Of note, we found a small number of genes expressed in neurons that were upregulated during clinical disease including, COX6A2, FZD9, RXRG and SOX11, that may be biomarkers of neurodegeneration.
format	article
author	Anna Majer Sarah J. Medina Debra Sorensen Matthew J. Martin Kathy L. Frost Clark Phillipson Kathy Manguiat Stephanie A. Booth
author_facet	Anna Majer Sarah J. Medina Debra Sorensen Matthew J. Martin Kathy L. Frost Clark Phillipson Kathy Manguiat Stephanie A. Booth
author_sort	Anna Majer
title	The cell type resolved mouse transcriptome in neuron-enriched brain tissues from the hippocampus and cerebellum during prion disease
title_short	The cell type resolved mouse transcriptome in neuron-enriched brain tissues from the hippocampus and cerebellum during prion disease
title_full	The cell type resolved mouse transcriptome in neuron-enriched brain tissues from the hippocampus and cerebellum during prion disease
title_fullStr	The cell type resolved mouse transcriptome in neuron-enriched brain tissues from the hippocampus and cerebellum during prion disease
title_full_unstemmed	The cell type resolved mouse transcriptome in neuron-enriched brain tissues from the hippocampus and cerebellum during prion disease
title_sort	cell type resolved mouse transcriptome in neuron-enriched brain tissues from the hippocampus and cerebellum during prion disease
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/a5215f0e0d6d49c7899b2cea69864fb5
work_keys_str_mv	AT annamajer thecelltyperesolvedmousetranscriptomeinneuronenrichedbraintissuesfromthehippocampusandcerebellumduringpriondisease AT sarahjmedina thecelltyperesolvedmousetranscriptomeinneuronenrichedbraintissuesfromthehippocampusandcerebellumduringpriondisease AT debrasorensen thecelltyperesolvedmousetranscriptomeinneuronenrichedbraintissuesfromthehippocampusandcerebellumduringpriondisease AT matthewjmartin thecelltyperesolvedmousetranscriptomeinneuronenrichedbraintissuesfromthehippocampusandcerebellumduringpriondisease AT kathylfrost thecelltyperesolvedmousetranscriptomeinneuronenrichedbraintissuesfromthehippocampusandcerebellumduringpriondisease AT clarkphillipson thecelltyperesolvedmousetranscriptomeinneuronenrichedbraintissuesfromthehippocampusandcerebellumduringpriondisease AT kathymanguiat thecelltyperesolvedmousetranscriptomeinneuronenrichedbraintissuesfromthehippocampusandcerebellumduringpriondisease AT stephanieabooth thecelltyperesolvedmousetranscriptomeinneuronenrichedbraintissuesfromthehippocampusandcerebellumduringpriondisease AT annamajer celltyperesolvedmousetranscriptomeinneuronenrichedbraintissuesfromthehippocampusandcerebellumduringpriondisease AT sarahjmedina celltyperesolvedmousetranscriptomeinneuronenrichedbraintissuesfromthehippocampusandcerebellumduringpriondisease AT debrasorensen celltyperesolvedmousetranscriptomeinneuronenrichedbraintissuesfromthehippocampusandcerebellumduringpriondisease AT matthewjmartin celltyperesolvedmousetranscriptomeinneuronenrichedbraintissuesfromthehippocampusandcerebellumduringpriondisease AT kathylfrost celltyperesolvedmousetranscriptomeinneuronenrichedbraintissuesfromthehippocampusandcerebellumduringpriondisease AT clarkphillipson celltyperesolvedmousetranscriptomeinneuronenrichedbraintissuesfromthehippocampusandcerebellumduringpriondisease AT kathymanguiat celltyperesolvedmousetranscriptomeinneuronenrichedbraintissuesfromthehippocampusandcerebellumduringpriondisease AT stephanieabooth celltyperesolvedmousetranscriptomeinneuronenrichedbraintissuesfromthehippocampusandcerebellumduringpriondisease
_version_	1718387771126579200

The cell type resolved mouse transcriptome in neuron-enriched brain tissues from the hippocampus and cerebellum during prion disease

Ejemplares similares