Simulated Microgravity Exerts an Age-Dependent Effect on the Differentiation of Cardiovascular Progenitors Isolated from the Human Heart
Microgravity has a profound effect on cardiovascular function, however, little is known about the impact of microgravity on progenitors that reside within the heart. We investigated the effect of simulated microgravity exposure on progenitors isolated from the neonatal and adult human heart by quant...
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| Veröffentlicht in: | PloS one 2015-07, Vol.10 (7), p.e0132378-e0132378 |
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| creator | Fuentes, Tania I Appleby, Nancy Raya, Michael Bailey, Leonard Hasaniya, Nahidh Stodieck, Louis Kearns-Jonker, Mary |
| description | Microgravity has a profound effect on cardiovascular function, however, little is known about the impact of microgravity on progenitors that reside within the heart. We investigated the effect of simulated microgravity exposure on progenitors isolated from the neonatal and adult human heart by quantifying changes in functional parameters, gene expression and protein levels after 6-7 days of 2D clinorotation. Utilization of neonatal and adult cardiovascular progenitors in ground-based studies has provided novel insight into how microgravity may affect cells differently depending on age. Simulated microgravity exposure did not impact AKT or ERK phosphorylation levels and did not influence cell migration, but elevated transcripts for paracrine factors were identified in neonatal and adult cardiovascular progenitors. Age-dependent responses surfaced when comparing the impact of microgravity on differentiation. Endothelial cell tube formation was unchanged or increased in progenitors from adults whereas neonatal cardiovascular progenitors showed a decline in tube formation (p |
| doi_str_mv | 10.1371/journal.pone.0132378 |
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We investigated the effect of simulated microgravity exposure on progenitors isolated from the neonatal and adult human heart by quantifying changes in functional parameters, gene expression and protein levels after 6-7 days of 2D clinorotation. Utilization of neonatal and adult cardiovascular progenitors in ground-based studies has provided novel insight into how microgravity may affect cells differently depending on age. Simulated microgravity exposure did not impact AKT or ERK phosphorylation levels and did not influence cell migration, but elevated transcripts for paracrine factors were identified in neonatal and adult cardiovascular progenitors. Age-dependent responses surfaced when comparing the impact of microgravity on differentiation. Endothelial cell tube formation was unchanged or increased in progenitors from adults whereas neonatal cardiovascular progenitors showed a decline in tube formation (p<0.05). Von Willebrand Factor, an endothelial differentiation marker, and MLC2v and Troponin T, markers for cardiomyogenic differentiation, were elevated in expression in adult progenitors after simulated microgravity. DNA repair genes and telomerase reverse transcriptase which are highly expressed in early stem cells were increased in expression in neonatal but not adult cardiac progenitors after growth under simulated microgravity conditions. Neonatal cardiac progenitors demonstrated higher levels of MESP1, OCT4, and brachyury, markers for early stem cells. MicroRNA profiling was used to further investigate the impact of simulated microgravity on cardiovascular progenitors. Fifteen microRNAs were significantly altered in expression, including microRNAs-99a and 100 (which play a critical role in cell dedifferentiation). These microRNAs were unchanged in adult cardiac progenitors. The effect of exposure to simulated microgravity in cardiovascular progenitors is age-dependent. Adult cardiac progenitors showed elevated expression of markers for endothelial and cardiomyogenic differentiation whereas neonatal progenitors acquired characteristics of dedifferentiating cells.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0132378</identifier><identifier>PMID: 26161778</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adults ; Age ; Aged ; Aging - physiology ; AKT protein ; Angiogenesis ; Biomarkers ; Calcium-binding protein ; Cancer ; Cardiomyocytes ; Cardiovascular system ; Cell Count ; Cell cycle ; Cell differentiation ; Cell Differentiation - drug effects ; Cell growth ; Cell migration ; Cell Movement - drug effects ; Cell Separation - methods ; Clinorotation ; Cloning ; Deoxyribonucleic acid ; Differentiation (biology) ; DNA ; DNA repair ; DNA Repair - genetics ; Embryos ; Endothelial cells ; Exposure ; Extracellular signal-regulated kinase ; Extracellular Signal-Regulated MAP Kinases - metabolism ; Flow cytometry ; Gene expression ; Gene Expression Profiling ; Gene Expression Regulation - drug effects ; Heart ; Heart diseases ; Heart surgery ; Humans ; Infant, Newborn ; Intercellular Signaling Peptides and Proteins - pharmacology ; Medicine ; Microgravity ; MicroRNA ; MicroRNAs ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Middle Aged ; miRNA ; Myocardium - cytology ; Neonates ; Oct-4 protein ; Paracrine signalling ; Pathology ; Phosphorylation ; Phosphorylation - drug effects ; Proto-Oncogene Proteins c-akt - metabolism ; Ribonucleic acid ; RNA ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; RNA-directed DNA polymerase ; Simulation ; Stem cells ; Stem Cells - cytology ; Stem Cells - drug effects ; Stem Cells - enzymology ; Telomerase ; Telomerase reverse transcriptase ; Troponin ; Troponin T ; Von Willebrand factor ; Weightlessness Simulation</subject><ispartof>PloS one, 2015-07, Vol.10 (7), p.e0132378-e0132378</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Fuentes et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Fuentes et al 2015 Fuentes et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-b3bc31a7d23f33bd2175bf2b00a91e6aab75e367b5a611b278e5d219cebd51333</citedby><cites>FETCH-LOGICAL-c692t-b3bc31a7d23f33bd2175bf2b00a91e6aab75e367b5a611b278e5d219cebd51333</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4498633/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4498633/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26161778$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Limana, Federica</contributor><creatorcontrib>Fuentes, Tania I</creatorcontrib><creatorcontrib>Appleby, Nancy</creatorcontrib><creatorcontrib>Raya, Michael</creatorcontrib><creatorcontrib>Bailey, Leonard</creatorcontrib><creatorcontrib>Hasaniya, Nahidh</creatorcontrib><creatorcontrib>Stodieck, Louis</creatorcontrib><creatorcontrib>Kearns-Jonker, Mary</creatorcontrib><title>Simulated Microgravity Exerts an Age-Dependent Effect on the Differentiation of Cardiovascular Progenitors Isolated from the Human Heart</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Microgravity has a profound effect on cardiovascular function, however, little is known about the impact of microgravity on progenitors that reside within the heart. We investigated the effect of simulated microgravity exposure on progenitors isolated from the neonatal and adult human heart by quantifying changes in functional parameters, gene expression and protein levels after 6-7 days of 2D clinorotation. Utilization of neonatal and adult cardiovascular progenitors in ground-based studies has provided novel insight into how microgravity may affect cells differently depending on age. Simulated microgravity exposure did not impact AKT or ERK phosphorylation levels and did not influence cell migration, but elevated transcripts for paracrine factors were identified in neonatal and adult cardiovascular progenitors. Age-dependent responses surfaced when comparing the impact of microgravity on differentiation. Endothelial cell tube formation was unchanged or increased in progenitors from adults whereas neonatal cardiovascular progenitors showed a decline in tube formation (p<0.05). Von Willebrand Factor, an endothelial differentiation marker, and MLC2v and Troponin T, markers for cardiomyogenic differentiation, were elevated in expression in adult progenitors after simulated microgravity. DNA repair genes and telomerase reverse transcriptase which are highly expressed in early stem cells were increased in expression in neonatal but not adult cardiac progenitors after growth under simulated microgravity conditions. Neonatal cardiac progenitors demonstrated higher levels of MESP1, OCT4, and brachyury, markers for early stem cells. MicroRNA profiling was used to further investigate the impact of simulated microgravity on cardiovascular progenitors. Fifteen microRNAs were significantly altered in expression, including microRNAs-99a and 100 (which play a critical role in cell dedifferentiation). These microRNAs were unchanged in adult cardiac progenitors. The effect of exposure to simulated microgravity in cardiovascular progenitors is age-dependent. Adult cardiac progenitors showed elevated expression of markers for endothelial and cardiomyogenic differentiation whereas neonatal progenitors acquired characteristics of dedifferentiating cells.</description><subject>Adults</subject><subject>Age</subject><subject>Aged</subject><subject>Aging - physiology</subject><subject>AKT protein</subject><subject>Angiogenesis</subject><subject>Biomarkers</subject><subject>Calcium-binding protein</subject><subject>Cancer</subject><subject>Cardiomyocytes</subject><subject>Cardiovascular system</subject><subject>Cell Count</subject><subject>Cell cycle</subject><subject>Cell differentiation</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell growth</subject><subject>Cell migration</subject><subject>Cell Movement - drug effects</subject><subject>Cell Separation - methods</subject><subject>Clinorotation</subject><subject>Cloning</subject><subject>Deoxyribonucleic acid</subject><subject>Differentiation (biology)</subject><subject>DNA</subject><subject>DNA repair</subject><subject>DNA Repair - genetics</subject><subject>Embryos</subject><subject>Endothelial cells</subject><subject>Exposure</subject><subject>Extracellular signal-regulated kinase</subject><subject>Extracellular Signal-Regulated MAP Kinases - metabolism</subject><subject>Flow cytometry</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Heart</subject><subject>Heart diseases</subject><subject>Heart surgery</subject><subject>Humans</subject><subject>Infant, Newborn</subject><subject>Intercellular Signaling Peptides and Proteins - pharmacology</subject><subject>Medicine</subject><subject>Microgravity</subject><subject>MicroRNA</subject><subject>MicroRNAs</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>Middle Aged</subject><subject>miRNA</subject><subject>Myocardium - cytology</subject><subject>Neonates</subject><subject>Oct-4 protein</subject><subject>Paracrine signalling</subject><subject>Pathology</subject><subject>Phosphorylation</subject><subject>Phosphorylation - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fuentes, Tania I</au><au>Appleby, Nancy</au><au>Raya, Michael</au><au>Bailey, Leonard</au><au>Hasaniya, Nahidh</au><au>Stodieck, Louis</au><au>Kearns-Jonker, Mary</au><au>Limana, Federica</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Simulated Microgravity Exerts an Age-Dependent Effect on the Differentiation of Cardiovascular Progenitors Isolated from the Human Heart</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-07-10</date><risdate>2015</risdate><volume>10</volume><issue>7</issue><spage>e0132378</spage><epage>e0132378</epage><pages>e0132378-e0132378</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Microgravity has a profound effect on cardiovascular function, however, little is known about the impact of microgravity on progenitors that reside within the heart. We investigated the effect of simulated microgravity exposure on progenitors isolated from the neonatal and adult human heart by quantifying changes in functional parameters, gene expression and protein levels after 6-7 days of 2D clinorotation. Utilization of neonatal and adult cardiovascular progenitors in ground-based studies has provided novel insight into how microgravity may affect cells differently depending on age. Simulated microgravity exposure did not impact AKT or ERK phosphorylation levels and did not influence cell migration, but elevated transcripts for paracrine factors were identified in neonatal and adult cardiovascular progenitors. Age-dependent responses surfaced when comparing the impact of microgravity on differentiation. Endothelial cell tube formation was unchanged or increased in progenitors from adults whereas neonatal cardiovascular progenitors showed a decline in tube formation (p<0.05). Von Willebrand Factor, an endothelial differentiation marker, and MLC2v and Troponin T, markers for cardiomyogenic differentiation, were elevated in expression in adult progenitors after simulated microgravity. DNA repair genes and telomerase reverse transcriptase which are highly expressed in early stem cells were increased in expression in neonatal but not adult cardiac progenitors after growth under simulated microgravity conditions. Neonatal cardiac progenitors demonstrated higher levels of MESP1, OCT4, and brachyury, markers for early stem cells. MicroRNA profiling was used to further investigate the impact of simulated microgravity on cardiovascular progenitors. Fifteen microRNAs were significantly altered in expression, including microRNAs-99a and 100 (which play a critical role in cell dedifferentiation). These microRNAs were unchanged in adult cardiac progenitors. The effect of exposure to simulated microgravity in cardiovascular progenitors is age-dependent. Adult cardiac progenitors showed elevated expression of markers for endothelial and cardiomyogenic differentiation whereas neonatal progenitors acquired characteristics of dedifferentiating cells.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26161778</pmid><doi>10.1371/journal.pone.0132378</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2015-07, Vol.10 (7), p.e0132378-e0132378 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1695377900 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adults Age Aged Aging - physiology AKT protein Angiogenesis Biomarkers Calcium-binding protein Cancer Cardiomyocytes Cardiovascular system Cell Count Cell cycle Cell differentiation Cell Differentiation - drug effects Cell growth Cell migration Cell Movement - drug effects Cell Separation - methods Clinorotation Cloning Deoxyribonucleic acid Differentiation (biology) DNA DNA repair DNA Repair - genetics Embryos Endothelial cells Exposure Extracellular signal-regulated kinase Extracellular Signal-Regulated MAP Kinases - metabolism Flow cytometry Gene expression Gene Expression Profiling Gene Expression Regulation - drug effects Heart Heart diseases Heart surgery Humans Infant, Newborn Intercellular Signaling Peptides and Proteins - pharmacology Medicine Microgravity MicroRNA MicroRNAs MicroRNAs - genetics MicroRNAs - metabolism Middle Aged miRNA Myocardium - cytology Neonates Oct-4 protein Paracrine signalling Pathology Phosphorylation Phosphorylation - drug effects Proto-Oncogene Proteins c-akt - metabolism Ribonucleic acid RNA RNA, Messenger - genetics RNA, Messenger - metabolism RNA-directed DNA polymerase Simulation Stem cells Stem Cells - cytology Stem Cells - drug effects Stem Cells - enzymology Telomerase Telomerase reverse transcriptase Troponin Troponin T Von Willebrand factor Weightlessness Simulation |
| title | Simulated Microgravity Exerts an Age-Dependent Effect on the Differentiation of Cardiovascular Progenitors Isolated from the Human Heart |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T18%3A21%3A57IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Simulated%20Microgravity%20Exerts%20an%20Age-Dependent%20Effect%20on%20the%20Differentiation%20of%20Cardiovascular%20Progenitors%20Isolated%20from%20the%20Human%20Heart&rft.jtitle=PloS%20one&rft.au=Fuentes,%20Tania%20I&rft.date=2015-07-10&rft.volume=10&rft.issue=7&rft.spage=e0132378&rft.epage=e0132378&rft.pages=e0132378-e0132378&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0132378&rft_dat=%3Cgale_plos_%3EA421278195%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1695377900&rft_id=info:pmid/26161778&rft_galeid=A421278195&rft_doaj_id=oai_doaj_org_article_e9ba6b38384e4393b515f2ecbffbdbe0&rfr_iscdi=true |