Células-tronco mesenquimais humanas e reparo de DNA: Uma análise in silico de dados de microarray
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Tipo de documento: | Trabalho de conclusão de curso |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFRN |
Texto Completo: | https://repositorio.ufrn.br/handle/123456789/43259 |
Resumo: | Human mesenchymal stem cells (hMSC) are multipotent stem cells of stromal origin. These cells have been widely used for cell therapy means in regenerative medicine due to their tissue diferentiation capacity as well as in vitro expansion and functional plasticity. The effects of senescence on genetic stability has been discussed througout the years, so that a previous study has found that stem cell senescence is associated with chromossomal abnormalities, which can explain the reason why these cells have been linked to age-related diseases such as cancer and Alzheimer’s disease. Furthermore, genetic instability can be responsible for the acquisition of tumorigenesis features in vitro and in vivo. In this study, the expression of DNA repair pathways of umbilical cord- derived hMSC harboring a paracentric chromosomal inversion (MSC/inv) was compared to a normal karyotype lineage (MSC/n) in early (Passage 9) and late (Passage 18) in vitro passages. Microarray data from these cell groups was analyzed through two in silico approaches: Gene Set Enrichment Analysis (GSEA) and gene prioritization (Endeavour). When compared to young stem cells, our results show that both groups of senescent stem cells present reduced DNA repair expression. By looking at the two groups of young stem cells, we found that there is no differential expression of DNA repair pathways between them, whereas senescent stem cell with inverted karyotype showed lower expression of DNA repair pathways. These findings support the idea that senescence alters DNA repair capacity of CTMs, given the inhibition of several DNA repair pathways, especially on MSCs/inv, which presented accentuated genetic instability. |
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Silva, Elielson Veloso daSilbiger, Vivian NogueiraLeal, Angélica Maria de Sousa2016-12-22T14:53:41Z2021-10-06T11:18:07Z2016-12-22T14:53:41Z2021-10-06T11:18:07Z2016-122011018240SILVA, Elielson Veloso da. Células-tronco mesenquimais humanas e reparo de DNA: Uma análise in silico de dados de microarray. 2016. 104 f. Trabalho de Conclusão de Curso (Graduação em Biomedicina)- Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, 2016.https://repositorio.ufrn.br/handle/123456789/43259Human mesenchymal stem cells (hMSC) are multipotent stem cells of stromal origin. These cells have been widely used for cell therapy means in regenerative medicine due to their tissue diferentiation capacity as well as in vitro expansion and functional plasticity. The effects of senescence on genetic stability has been discussed througout the years, so that a previous study has found that stem cell senescence is associated with chromossomal abnormalities, which can explain the reason why these cells have been linked to age-related diseases such as cancer and Alzheimer’s disease. Furthermore, genetic instability can be responsible for the acquisition of tumorigenesis features in vitro and in vivo. In this study, the expression of DNA repair pathways of umbilical cord- derived hMSC harboring a paracentric chromosomal inversion (MSC/inv) was compared to a normal karyotype lineage (MSC/n) in early (Passage 9) and late (Passage 18) in vitro passages. Microarray data from these cell groups was analyzed through two in silico approaches: Gene Set Enrichment Analysis (GSEA) and gene prioritization (Endeavour). When compared to young stem cells, our results show that both groups of senescent stem cells present reduced DNA repair expression. By looking at the two groups of young stem cells, we found that there is no differential expression of DNA repair pathways between them, whereas senescent stem cell with inverted karyotype showed lower expression of DNA repair pathways. These findings support the idea that senescence alters DNA repair capacity of CTMs, given the inhibition of several DNA repair pathways, especially on MSCs/inv, which presented accentuated genetic instability.Células-tronco mesenquimais, do inglês Mesenchymal Stem cells (hMSC) são células multipotentes de origem estromal. Essas células têm sido amplamente utilizadas no campo da medicina regenerativa devido a sua capacidade de diferenciação tecidual, plasticidade funcional, bem como possibilidade de expansão in vitro. Os efeitos da senescência na estabilidade genética têm sido discutidos ao longo dos anos, de modo que um estudo anterior observou que a senescência em células-tronco mesenquimais está associada com anormalidades cromossômicas, o que pode levar ao surgimento de doenças relacionadas à idade, tais como câncer e Alzheimer, já que, por exemplo, a instabilidade genética pode ser responsável pela aquisição de características tumorigênicas tanto in vitro como in vivo. Nesse estudo, a expressão de vias de reparo de DNA em células-tronco mesenquimais humanas extraídas do cordão umbilical e que apresentam uma inversão cromossômica paracêntrica constitucional (CTMs/inv) foi comparada à expressão em células-tronco com cariótipo normal (CTMs/norm) quando jovens (Passagem 9) e senescentes (Passagem 18). Os dados de microarranjo desses grupos celulares foram analisados in silico através de duas ferramentas de bioinformática, Gene Set Enrichiment Analysis (GSEA) e Gene Prioritization (Endeavour). Os resultados mostraram que, quando comparadas com as células jovens, ambos os grupos de células senescentes apresentaram vias de reparo de DNA menos expressas. Já ao analisarmos os dois grupos de células jovens, não foi observada expressão diferencial de vias de reparo de DNA, enquanto que CTMs/inv possuem vias de reparo de DNA menos expressas em comparação com as células normais senescentes. Esses resultados sugerem que a senescência afeta a capacidade que as células tronco possuem de reparar danos no DNA, dada a inibição de diversas vias de reparo, principalmente em CTMs/inv, que apresentam instabilidade genética acentuada.Universidade Federal do Rio Grande do NorteUFRNBrasilBiomedicinaCélulas-tronco mesenquimais humanas (CTMs)SenescênciaReparo de DNAInstabilidade genéticaCélulas-tronco mesenquimais humanas e reparo de DNA: Uma análise in silico de dados de microarrayinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/bachelorThesisinfo:eu-repo/semantics/openAccessporreponame:Repositório Institucional da UFRNinstname:Universidade Federal do Rio Grande do Norte (UFRN)instacron:UFRNTEXTCélulastroncoMesenquimais_Silva_2016.pdf.txtExtracted texttext/plain168129https://repositorio.ufrn.br/bitstream/123456789/43259/1/C%c3%a9lulastroncoMesenquimais_Silva_2016.pdf.txt2366772546e08d5e199dc346ef09521bMD51Células-troncoMesenquimaisHumanas_Silva_2016.pdf.txtExtracted texttext/plain168129https://repositorio.ufrn.br/bitstream/123456789/43259/2/C%c3%a9lulas-troncoMesenquimaisHumanas_Silva_2016.pdf.txt2366772546e08d5e199dc346ef09521bMD52LICENSElicense.txttext/plain756https://repositorio.ufrn.br/bitstream/123456789/43259/3/license.txta80a9cda2756d355b388cc443c3d8a43MD53ORIGINALCélulas-troncoMesenquimaisHumanas_Silva_2016.pdfMonografiaapplication/pdf2755246https://repositorio.ufrn.br/bitstream/123456789/43259/4/C%c3%a9lulas-troncoMesenquimaisHumanas_Silva_2016.pdfb550c71bc8e46454a54c49cbd12b2c8aMD54123456789/432592021-10-06 08:18:08.039oai:https://repositorio.ufrn.br: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ório de PublicaçõesPUBhttp://repositorio.ufrn.br/oai/opendoar:2021-10-06T11:18:08Repositório Institucional da UFRN - Universidade Federal do Rio Grande do Norte (UFRN)false |
dc.title.pr_BR.fl_str_mv |
Células-tronco mesenquimais humanas e reparo de DNA: Uma análise in silico de dados de microarray |
title |
Células-tronco mesenquimais humanas e reparo de DNA: Uma análise in silico de dados de microarray |
spellingShingle |
Células-tronco mesenquimais humanas e reparo de DNA: Uma análise in silico de dados de microarray Silva, Elielson Veloso da Células-tronco mesenquimais humanas (CTMs) Senescência Reparo de DNA Instabilidade genética |
title_short |
Células-tronco mesenquimais humanas e reparo de DNA: Uma análise in silico de dados de microarray |
title_full |
Células-tronco mesenquimais humanas e reparo de DNA: Uma análise in silico de dados de microarray |
title_fullStr |
Células-tronco mesenquimais humanas e reparo de DNA: Uma análise in silico de dados de microarray |
title_full_unstemmed |
Células-tronco mesenquimais humanas e reparo de DNA: Uma análise in silico de dados de microarray |
title_sort |
Células-tronco mesenquimais humanas e reparo de DNA: Uma análise in silico de dados de microarray |
author |
Silva, Elielson Veloso da |
author_facet |
Silva, Elielson Veloso da |
author_role |
author |
dc.contributor.referees1.none.fl_str_mv |
Silbiger, Vivian Nogueira |
dc.contributor.referees2.none.fl_str_mv |
Leal, Angélica Maria de Sousa |
dc.contributor.author.fl_str_mv |
Silva, Elielson Veloso da |
dc.subject.pr_BR.fl_str_mv |
Células-tronco mesenquimais humanas (CTMs) Senescência Reparo de DNA Instabilidade genética |
topic |
Células-tronco mesenquimais humanas (CTMs) Senescência Reparo de DNA Instabilidade genética |
description |
Human mesenchymal stem cells (hMSC) are multipotent stem cells of stromal origin. These cells have been widely used for cell therapy means in regenerative medicine due to their tissue diferentiation capacity as well as in vitro expansion and functional plasticity. The effects of senescence on genetic stability has been discussed througout the years, so that a previous study has found that stem cell senescence is associated with chromossomal abnormalities, which can explain the reason why these cells have been linked to age-related diseases such as cancer and Alzheimer’s disease. Furthermore, genetic instability can be responsible for the acquisition of tumorigenesis features in vitro and in vivo. In this study, the expression of DNA repair pathways of umbilical cord- derived hMSC harboring a paracentric chromosomal inversion (MSC/inv) was compared to a normal karyotype lineage (MSC/n) in early (Passage 9) and late (Passage 18) in vitro passages. Microarray data from these cell groups was analyzed through two in silico approaches: Gene Set Enrichment Analysis (GSEA) and gene prioritization (Endeavour). When compared to young stem cells, our results show that both groups of senescent stem cells present reduced DNA repair expression. By looking at the two groups of young stem cells, we found that there is no differential expression of DNA repair pathways between them, whereas senescent stem cell with inverted karyotype showed lower expression of DNA repair pathways. These findings support the idea that senescence alters DNA repair capacity of CTMs, given the inhibition of several DNA repair pathways, especially on MSCs/inv, which presented accentuated genetic instability. |
publishDate |
2016 |
dc.date.accessioned.fl_str_mv |
2016-12-22T14:53:41Z 2021-10-06T11:18:07Z |
dc.date.available.fl_str_mv |
2016-12-22T14:53:41Z 2021-10-06T11:18:07Z |
dc.date.issued.fl_str_mv |
2016-12 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/bachelorThesis |
format |
bachelorThesis |
status_str |
publishedVersion |
dc.identifier.pr_BR.fl_str_mv |
2011018240 |
dc.identifier.citation.fl_str_mv |
SILVA, Elielson Veloso da. Células-tronco mesenquimais humanas e reparo de DNA: Uma análise in silico de dados de microarray. 2016. 104 f. Trabalho de Conclusão de Curso (Graduação em Biomedicina)- Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, 2016. |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufrn.br/handle/123456789/43259 |
identifier_str_mv |
2011018240 SILVA, Elielson Veloso da. Células-tronco mesenquimais humanas e reparo de DNA: Uma análise in silico de dados de microarray. 2016. 104 f. Trabalho de Conclusão de Curso (Graduação em Biomedicina)- Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, 2016. |
url |
https://repositorio.ufrn.br/handle/123456789/43259 |
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Universidade Federal do Rio Grande do Norte |
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UFRN |
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Brasil |
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Biomedicina |
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Universidade Federal do Rio Grande do Norte |
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