Systems Biology-Based Analysis Indicates Global Transcriptional Impairment in Lead-Treated Human Neural Progenitor Cells
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/200510 |
Resumo: | Lead poisoning effects are wide and include nervous system impairment, peculiarly during development, leading to neural damage. Lead interaction with calcium and zinc-containing metalloproteins broadly affects cellular metabolism since these proteins are related to intracellular ion balance, activation of signaling transduction cascades, and gene expression regulation. In spite of lead being recognized as a neurotoxin, there are gaps in knowledge about the global effect of lead in modulating the transcription of entire cellular systems in neural cells. In order to investigate the effects of lead poisoning in a systemic perspective, we applied the transcriptogram methodology in an RNA-seq dataset of human embryonic-derived neural progenitor cells (ES-NP cells) treated with 30 µM lead acetate for 26 days. We observed early downregulation of several cellular systems involved with cell differentiation, such as cytoskeleton organization, RNA, and protein biosynthesis. The downregulated cellular systems presented big and tightly connected networks. For long treatment times (12 to 26 days), it was possible to observe a massive impairment in cell transcription profile. Taking the enriched terms together, we observed interference in all layers of gene expression regulation, from chromatin remodeling to vesicle transport. Considering that ES-NP cells are progenitor cells that can originate other neural cell types, our results suggest that lead-induced gene expression disturbance might impair cells’ ability to differentiate, therefore influencing ES-NP cells’ fate. |
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Reis, Clovis Ferreira dosSouza, Iara Dantas deMorais, Diego Arthur de AzevedoOliveira, Raffael AzevedoImparato, Danilo OliveiraAlmeida, Rita Maria Cunha deDalmolin, Rodrigo Juliani Siqueira2019-10-11T03:54:43Z20171664-8021http://hdl.handle.net/10183/200510001103720Lead poisoning effects are wide and include nervous system impairment, peculiarly during development, leading to neural damage. Lead interaction with calcium and zinc-containing metalloproteins broadly affects cellular metabolism since these proteins are related to intracellular ion balance, activation of signaling transduction cascades, and gene expression regulation. In spite of lead being recognized as a neurotoxin, there are gaps in knowledge about the global effect of lead in modulating the transcription of entire cellular systems in neural cells. In order to investigate the effects of lead poisoning in a systemic perspective, we applied the transcriptogram methodology in an RNA-seq dataset of human embryonic-derived neural progenitor cells (ES-NP cells) treated with 30 µM lead acetate for 26 days. We observed early downregulation of several cellular systems involved with cell differentiation, such as cytoskeleton organization, RNA, and protein biosynthesis. The downregulated cellular systems presented big and tightly connected networks. For long treatment times (12 to 26 days), it was possible to observe a massive impairment in cell transcription profile. Taking the enriched terms together, we observed interference in all layers of gene expression regulation, from chromatin remodeling to vesicle transport. Considering that ES-NP cells are progenitor cells that can originate other neural cell types, our results suggest that lead-induced gene expression disturbance might impair cells’ ability to differentiate, therefore influencing ES-NP cells’ fate.application/pdfengFrontiers in Genetics. Lausanne. Vol. 10 (Sep. 2019), art. 791, p. 1-11Metabolismo celularChumboRNATranscriptogramaLead exposureLead poisoningTranscriptogramerRNA-seqTranscriptome analysisNetwork inferenceData integrationnetwork visualizationSystems Biology-Based Analysis Indicates Global Transcriptional Impairment in Lead-Treated Human Neural Progenitor CellsEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSTEXT001103720.pdf.txt001103720.pdf.txtExtracted Texttext/plain56813http://www.lume.ufrgs.br/bitstream/10183/200510/2/001103720.pdf.txt63a96f5198eaf4a9cad9ba7e51d73f5bMD52ORIGINAL001103720.pdfTexto completo (inglês)application/pdf3541760http://www.lume.ufrgs.br/bitstream/10183/200510/1/001103720.pdfaba13511bc9807138bc1ca87158590f8MD5110183/2005102024-03-29 06:17:24.527167oai:www.lume.ufrgs.br:10183/200510Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2024-03-29T09:17:24Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
Systems Biology-Based Analysis Indicates Global Transcriptional Impairment in Lead-Treated Human Neural Progenitor Cells |
title |
Systems Biology-Based Analysis Indicates Global Transcriptional Impairment in Lead-Treated Human Neural Progenitor Cells |
spellingShingle |
Systems Biology-Based Analysis Indicates Global Transcriptional Impairment in Lead-Treated Human Neural Progenitor Cells Reis, Clovis Ferreira dos Metabolismo celular Chumbo RNA Transcriptograma Lead exposure Lead poisoning Transcriptogramer RNA-seq Transcriptome analysis Network inference Data integration network visualization |
title_short |
Systems Biology-Based Analysis Indicates Global Transcriptional Impairment in Lead-Treated Human Neural Progenitor Cells |
title_full |
Systems Biology-Based Analysis Indicates Global Transcriptional Impairment in Lead-Treated Human Neural Progenitor Cells |
title_fullStr |
Systems Biology-Based Analysis Indicates Global Transcriptional Impairment in Lead-Treated Human Neural Progenitor Cells |
title_full_unstemmed |
Systems Biology-Based Analysis Indicates Global Transcriptional Impairment in Lead-Treated Human Neural Progenitor Cells |
title_sort |
Systems Biology-Based Analysis Indicates Global Transcriptional Impairment in Lead-Treated Human Neural Progenitor Cells |
author |
Reis, Clovis Ferreira dos |
author_facet |
Reis, Clovis Ferreira dos Souza, Iara Dantas de Morais, Diego Arthur de Azevedo Oliveira, Raffael Azevedo Imparato, Danilo Oliveira Almeida, Rita Maria Cunha de Dalmolin, Rodrigo Juliani Siqueira |
author_role |
author |
author2 |
Souza, Iara Dantas de Morais, Diego Arthur de Azevedo Oliveira, Raffael Azevedo Imparato, Danilo Oliveira Almeida, Rita Maria Cunha de Dalmolin, Rodrigo Juliani Siqueira |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Reis, Clovis Ferreira dos Souza, Iara Dantas de Morais, Diego Arthur de Azevedo Oliveira, Raffael Azevedo Imparato, Danilo Oliveira Almeida, Rita Maria Cunha de Dalmolin, Rodrigo Juliani Siqueira |
dc.subject.por.fl_str_mv |
Metabolismo celular Chumbo RNA Transcriptograma |
topic |
Metabolismo celular Chumbo RNA Transcriptograma Lead exposure Lead poisoning Transcriptogramer RNA-seq Transcriptome analysis Network inference Data integration network visualization |
dc.subject.eng.fl_str_mv |
Lead exposure Lead poisoning Transcriptogramer RNA-seq Transcriptome analysis Network inference Data integration network visualization |
description |
Lead poisoning effects are wide and include nervous system impairment, peculiarly during development, leading to neural damage. Lead interaction with calcium and zinc-containing metalloproteins broadly affects cellular metabolism since these proteins are related to intracellular ion balance, activation of signaling transduction cascades, and gene expression regulation. In spite of lead being recognized as a neurotoxin, there are gaps in knowledge about the global effect of lead in modulating the transcription of entire cellular systems in neural cells. In order to investigate the effects of lead poisoning in a systemic perspective, we applied the transcriptogram methodology in an RNA-seq dataset of human embryonic-derived neural progenitor cells (ES-NP cells) treated with 30 µM lead acetate for 26 days. We observed early downregulation of several cellular systems involved with cell differentiation, such as cytoskeleton organization, RNA, and protein biosynthesis. The downregulated cellular systems presented big and tightly connected networks. For long treatment times (12 to 26 days), it was possible to observe a massive impairment in cell transcription profile. Taking the enriched terms together, we observed interference in all layers of gene expression regulation, from chromatin remodeling to vesicle transport. Considering that ES-NP cells are progenitor cells that can originate other neural cell types, our results suggest that lead-induced gene expression disturbance might impair cells’ ability to differentiate, therefore influencing ES-NP cells’ fate. |
publishDate |
2017 |
dc.date.issued.fl_str_mv |
2017 |
dc.date.accessioned.fl_str_mv |
2019-10-11T03:54:43Z |
dc.type.driver.fl_str_mv |
Estrangeiro info:eu-repo/semantics/article |
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info:eu-repo/semantics/publishedVersion |
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article |
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http://hdl.handle.net/10183/200510 |
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1664-8021 |
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001103720 |
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1664-8021 001103720 |
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http://hdl.handle.net/10183/200510 |
dc.language.iso.fl_str_mv |
eng |
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eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
Frontiers in Genetics. Lausanne. Vol. 10 (Sep. 2019), art. 791, p. 1-11 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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