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Transcriptional regulation induced by cAMP elevation in mouse Schwann cells.

Schmid D, Zeis T, Schaeren-Wiemers N - ASN Neuro (2014)

Bottom Line: One of the strongest differentially regulated gene transcripts was the transcription factor Olig1 (oligodendrocyte transcription factor 1), whose mRNA expression levels were reduced in treated Schwann cells.Olig1 protein was localized in myelinating and nonmyelinating Schwann cells within the sciatic nerve as well as in primary Schwann cells, proposing it as a novel transcription factor of the Schwann cell lineage.Data analysis further revealed that a number of differentially expressed genes in forskolin-treated Schwann cells were associated with the ECM (extracellular matrix), underlining its importance during Schwann cell differentiation in vitro.

View Article: PubMed Central - PubMed

Affiliation: *Neurobiology, Department of Biomedicine, University Hospital Basel, University of Basel, Hebelstrasse 20, CH-4031 Basel, Switzerland.

ABSTRACT
In peripheral nerves, Schwann cell development is regulated by a variety of signals. Some of the aspects of Schwann cell differentiation can be reproduced in vitro in response to forskolin, an adenylyl cyclase activator elevating intracellular cAMP levels. Herein, the effect of forskolin treatment was investigated by a comprehensive genome-wide expression study on primary mouse Schwann cell cultures. Additional to myelin-related genes, many so far unconsidered genes were ascertained to be modulated by forskolin. One of the strongest differentially regulated gene transcripts was the transcription factor Olig1 (oligodendrocyte transcription factor 1), whose mRNA expression levels were reduced in treated Schwann cells. Olig1 protein was localized in myelinating and nonmyelinating Schwann cells within the sciatic nerve as well as in primary Schwann cells, proposing it as a novel transcription factor of the Schwann cell lineage. Data analysis further revealed that a number of differentially expressed genes in forskolin-treated Schwann cells were associated with the ECM (extracellular matrix), underlining its importance during Schwann cell differentiation in vitro. Comparison of samples derived from postnatal sciatic nerves and from both treated and untreated Schwann cell cultures showed considerable differences in gene expression between in vivo and in vitro, allowing us to separate Schwann cell autonomous from tissue-related changes. The whole data set of the cell culture microarray study is provided to offer an interactive search tool for genes of interest.

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Comparison analysis of gene expression between primary mouse Schwann                            cell cultures and developing sciatic nerve samples                        (A, B) Analysis of the whole-genome revealed distinct gene transcription                            between in vivo and                                in vitro, illustrated by PCA (A). A                            well-defined cluster can be depicted of developing nerve samples,                            whereas P60 form an individual cluster. Distinct expression between                            primary Schwann cell cultures and in vivo                            samples could be confirmed by a heat map analysis, indicated by the                            dendrogram (B). (C, D) Analysis based on only forskolin-dependent                            differentially expressed transcripts resulted in distinct clusters                            between treated and untreated Schwann cells, as well as between                                in vivo and                                in vitro (C). Heat map analysis revealed                            that forskolin-treated Schwann cells associate within the same branch as                            the samples derived from the nerve tissues (D, arrow).
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Figure 5: Comparison analysis of gene expression between primary mouse Schwann cell cultures and developing sciatic nerve samples (A, B) Analysis of the whole-genome revealed distinct gene transcription between in vivo and in vitro, illustrated by PCA (A). A well-defined cluster can be depicted of developing nerve samples, whereas P60 form an individual cluster. Distinct expression between primary Schwann cell cultures and in vivo samples could be confirmed by a heat map analysis, indicated by the dendrogram (B). (C, D) Analysis based on only forskolin-dependent differentially expressed transcripts resulted in distinct clusters between treated and untreated Schwann cells, as well as between in vivo and in vitro (C). Heat map analysis revealed that forskolin-treated Schwann cells associate within the same branch as the samples derived from the nerve tissues (D, arrow).

Mentions: Elevation of intracellular cAMP by forskolin is often used as an in vitro model for Schwann cell differentiation. Therefore the expression data from naive and forskolin-treated Schwann cells and from sciatic nerve tissues taken from P0, P4, P7, P10 and P60 mice were examined by a PCA to visualize similarities or differences between the experimental samples (Figure 5A). Well-defined clusters could be identified for both untreated and treated Schwann cell cultures (Figure 5A, red and blue dots, respectively). Additional distinct clusters could be detected for samples of the different developmental time points of peripheral nerves (Figure 5A, green dots). The PCA for the developmental in vivo samples at P0, P4, P7 and P10 showed that the time points closely neighbor each other. P60 nerve samples formed an individual cluster, reflecting that their expression is distinct. The PCA also illustrated that the expression pattern identified in cultured Schwann cells did not overlap with those of the peripheral nerve tissues, which is reflected by the dendrogram analysis of hierarchical clustering (Figure 5B).


Transcriptional regulation induced by cAMP elevation in mouse Schwann cells.

Schmid D, Zeis T, Schaeren-Wiemers N - ASN Neuro (2014)

Comparison analysis of gene expression between primary mouse Schwann                            cell cultures and developing sciatic nerve samples                        (A, B) Analysis of the whole-genome revealed distinct gene transcription                            between in vivo and                                in vitro, illustrated by PCA (A). A                            well-defined cluster can be depicted of developing nerve samples,                            whereas P60 form an individual cluster. Distinct expression between                            primary Schwann cell cultures and in vivo                            samples could be confirmed by a heat map analysis, indicated by the                            dendrogram (B). (C, D) Analysis based on only forskolin-dependent                            differentially expressed transcripts resulted in distinct clusters                            between treated and untreated Schwann cells, as well as between                                in vivo and                                in vitro (C). Heat map analysis revealed                            that forskolin-treated Schwann cells associate within the same branch as                            the samples derived from the nerve tissues (D, arrow).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 5: Comparison analysis of gene expression between primary mouse Schwann cell cultures and developing sciatic nerve samples (A, B) Analysis of the whole-genome revealed distinct gene transcription between in vivo and in vitro, illustrated by PCA (A). A well-defined cluster can be depicted of developing nerve samples, whereas P60 form an individual cluster. Distinct expression between primary Schwann cell cultures and in vivo samples could be confirmed by a heat map analysis, indicated by the dendrogram (B). (C, D) Analysis based on only forskolin-dependent differentially expressed transcripts resulted in distinct clusters between treated and untreated Schwann cells, as well as between in vivo and in vitro (C). Heat map analysis revealed that forskolin-treated Schwann cells associate within the same branch as the samples derived from the nerve tissues (D, arrow).
Mentions: Elevation of intracellular cAMP by forskolin is often used as an in vitro model for Schwann cell differentiation. Therefore the expression data from naive and forskolin-treated Schwann cells and from sciatic nerve tissues taken from P0, P4, P7, P10 and P60 mice were examined by a PCA to visualize similarities or differences between the experimental samples (Figure 5A). Well-defined clusters could be identified for both untreated and treated Schwann cell cultures (Figure 5A, red and blue dots, respectively). Additional distinct clusters could be detected for samples of the different developmental time points of peripheral nerves (Figure 5A, green dots). The PCA for the developmental in vivo samples at P0, P4, P7 and P10 showed that the time points closely neighbor each other. P60 nerve samples formed an individual cluster, reflecting that their expression is distinct. The PCA also illustrated that the expression pattern identified in cultured Schwann cells did not overlap with those of the peripheral nerve tissues, which is reflected by the dendrogram analysis of hierarchical clustering (Figure 5B).

Bottom Line: One of the strongest differentially regulated gene transcripts was the transcription factor Olig1 (oligodendrocyte transcription factor 1), whose mRNA expression levels were reduced in treated Schwann cells.Olig1 protein was localized in myelinating and nonmyelinating Schwann cells within the sciatic nerve as well as in primary Schwann cells, proposing it as a novel transcription factor of the Schwann cell lineage.Data analysis further revealed that a number of differentially expressed genes in forskolin-treated Schwann cells were associated with the ECM (extracellular matrix), underlining its importance during Schwann cell differentiation in vitro.

View Article: PubMed Central - PubMed

Affiliation: *Neurobiology, Department of Biomedicine, University Hospital Basel, University of Basel, Hebelstrasse 20, CH-4031 Basel, Switzerland.

ABSTRACT
In peripheral nerves, Schwann cell development is regulated by a variety of signals. Some of the aspects of Schwann cell differentiation can be reproduced in vitro in response to forskolin, an adenylyl cyclase activator elevating intracellular cAMP levels. Herein, the effect of forskolin treatment was investigated by a comprehensive genome-wide expression study on primary mouse Schwann cell cultures. Additional to myelin-related genes, many so far unconsidered genes were ascertained to be modulated by forskolin. One of the strongest differentially regulated gene transcripts was the transcription factor Olig1 (oligodendrocyte transcription factor 1), whose mRNA expression levels were reduced in treated Schwann cells. Olig1 protein was localized in myelinating and nonmyelinating Schwann cells within the sciatic nerve as well as in primary Schwann cells, proposing it as a novel transcription factor of the Schwann cell lineage. Data analysis further revealed that a number of differentially expressed genes in forskolin-treated Schwann cells were associated with the ECM (extracellular matrix), underlining its importance during Schwann cell differentiation in vitro. Comparison of samples derived from postnatal sciatic nerves and from both treated and untreated Schwann cell cultures showed considerable differences in gene expression between in vivo and in vitro, allowing us to separate Schwann cell autonomous from tissue-related changes. The whole data set of the cell culture microarray study is provided to offer an interactive search tool for genes of interest.

Show MeSH
Related in: MedlinePlus