Collagen Type I Improves the Differentiation of Human Embryonic Stem Cells towards Definitive Endoderm
Human embryonic stem cells have the ability to generate all cell types in the body and can potentially provide an unlimited source of cells for cell replacement therapy to treat degenerative diseases such as diabetes. Current differentiation protocols of human embryonic stem cells towards insulin pr...
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description | Human embryonic stem cells have the ability to generate all cell types in the body and can potentially provide an unlimited source of cells for cell replacement therapy to treat degenerative diseases such as diabetes. Current differentiation protocols of human embryonic stem cells towards insulin producing beta cells focus on soluble molecules whereas the impact of cell-matrix interactions has been mainly unattended. In this study almost 500 different extracellular matrix protein combinations were screened to systemically identify extracellular matrix proteins that influence differentiation of human embryonic stem cells to the definitive endoderm lineage. The percentage of definitive endoderm cells after differentiation on collagen I and fibronectin was >85% and 65%, respectively. The cells on collagen I substrates displayed different morphology and gene expression during differentiation as assessed by time lapse studies compared to cells on the other tested substrates. Global gene expression analysis showed that cells differentiated on collagen I were largely similar to cells on fibronectin after completed differentiation. Collectively, the data suggest that collagen I induces a more rapid and consistent differentiation of stem cells to definitive endoderm. The results shed light on the importance of extracellular matrix proteins for differentiation and also points to a cost effective and easy method to improve differentiation. |
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Current differentiation protocols of human embryonic stem cells towards insulin producing beta cells focus on soluble molecules whereas the impact of cell-matrix interactions has been mainly unattended. In this study almost 500 different extracellular matrix protein combinations were screened to systemically identify extracellular matrix proteins that influence differentiation of human embryonic stem cells to the definitive endoderm lineage. The percentage of definitive endoderm cells after differentiation on collagen I and fibronectin was >85% and 65%, respectively. The cells on collagen I substrates displayed different morphology and gene expression during differentiation as assessed by time lapse studies compared to cells on the other tested substrates. Global gene expression analysis showed that cells differentiated on collagen I were largely similar to cells on fibronectin after completed differentiation. Collectively, the data suggest that collagen I induces a more rapid and consistent differentiation of stem cells to definitive endoderm. The results shed light on the importance of extracellular matrix proteins for differentiation and also points to a cost effective and easy method to improve differentiation.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0145389</identifier><identifier>PMID: 26713616</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Beta cells ; Cancer ; Cell adhesion & migration ; Cell culture ; Cell Differentiation ; Collagen ; Collagen (type I) ; Collagen Type I - metabolism ; Degenerative diseases ; Diabetes mellitus ; Diabetes therapy ; Differentiation ; Embryo cells ; Embryonic stem cells ; Embryos ; Endoderm ; Endoderm - cytology ; Extracellular matrix ; Fibroblasts ; Fibronectin ; Fibronectins ; Gene expression ; Gene Expression Profiling ; Growth factors ; Human Embryonic Stem Cells - cytology ; Human Embryonic Stem Cells - metabolism ; Humans ; Insulin ; Kinases ; Kinetics ; Matrix protein ; Proteins ; Stem cell research ; Stem cells ; Substrates</subject><ispartof>PloS one, 2015-12, Vol.10 (12), p.e0145389-e0145389</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Rasmussen 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 Rasmussen et al 2015 Rasmussen et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-ef0bf526504cda9aafcf2b3b61f0c258005bdc7f5b0c72ca9e43db7295a9bf943</citedby><cites>FETCH-LOGICAL-c692t-ef0bf526504cda9aafcf2b3b61f0c258005bdc7f5b0c72ca9e43db7295a9bf943</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/PMC4694921/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694921/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,2096,2915,23847,27905,27906,53772,53774,79349,79350</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26713616$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Lako, Majlinda</contributor><creatorcontrib>Rasmussen, Camilla Holzmann</creatorcontrib><creatorcontrib>Petersen, Dorthe Roenn</creatorcontrib><creatorcontrib>Moeller, Jonas Bech</creatorcontrib><creatorcontrib>Hansson, Mattias</creatorcontrib><creatorcontrib>Dufva, Martin</creatorcontrib><title>Collagen Type I Improves the Differentiation of Human Embryonic Stem Cells towards Definitive Endoderm</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Human embryonic stem cells have the ability to generate all cell types in the body and can potentially provide an unlimited source of cells for cell replacement therapy to treat degenerative diseases such as diabetes. Current differentiation protocols of human embryonic stem cells towards insulin producing beta cells focus on soluble molecules whereas the impact of cell-matrix interactions has been mainly unattended. In this study almost 500 different extracellular matrix protein combinations were screened to systemically identify extracellular matrix proteins that influence differentiation of human embryonic stem cells to the definitive endoderm lineage. The percentage of definitive endoderm cells after differentiation on collagen I and fibronectin was >85% and 65%, respectively. The cells on collagen I substrates displayed different morphology and gene expression during differentiation as assessed by time lapse studies compared to cells on the other tested substrates. Global gene expression analysis showed that cells differentiated on collagen I were largely similar to cells on fibronectin after completed differentiation. Collectively, the data suggest that collagen I induces a more rapid and consistent differentiation of stem cells to definitive endoderm. The results shed light on the importance of extracellular matrix proteins for differentiation and also points to a cost effective and easy method to improve differentiation.</description><subject>Analysis</subject><subject>Beta cells</subject><subject>Cancer</subject><subject>Cell adhesion & migration</subject><subject>Cell culture</subject><subject>Cell Differentiation</subject><subject>Collagen</subject><subject>Collagen (type I)</subject><subject>Collagen Type I - metabolism</subject><subject>Degenerative diseases</subject><subject>Diabetes mellitus</subject><subject>Diabetes therapy</subject><subject>Differentiation</subject><subject>Embryo cells</subject><subject>Embryonic stem cells</subject><subject>Embryos</subject><subject>Endoderm</subject><subject>Endoderm - cytology</subject><subject>Extracellular matrix</subject><subject>Fibroblasts</subject><subject>Fibronectin</subject><subject>Fibronectins</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Growth factors</subject><subject>Human Embryonic Stem Cells - cytology</subject><subject>Human Embryonic Stem Cells - metabolism</subject><subject>Humans</subject><subject>Insulin</subject><subject>Kinases</subject><subject>Kinetics</subject><subject>Matrix protein</subject><subject>Proteins</subject><subject>Stem cell research</subject><subject>Stem cells</subject><subject>Substrates</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk11v0zAUhiMEYmPwDxBYQkJw0eKPxG5ukKausEqTJrHBreU4x62nxC52Uui_x6Hd1KBdoFwktp_3PTnH52TZa4KnhAny6c73walmuvEOppjkBZuVT7JTUjI64RSzp0ffJ9mLGO8wTgznz7MTygVhnPDTzMx906gVOHS72wBaomW7CX4LEXVrQBfWGAjgOqs66x3yBl32rXJo0VZh553V6KaDFs2haZLC_1KhjugCjHW2s1tAC1f7GkL7MntmVBPh1eF9ln3_sridX06urr8u5-dXE81L2k3A4MoUlBc417UqlTLa0IpVnBisaTFLGVS1FqaosBZUqxJyVleCloUqK1Pm7Cx7u_fdND7KQ4miJKKgrGBMzBKx3BO1V3dyE2yrwk56ZeXfDR9WUoXO6gakLvCMi7JgVSFyATQtsNK5ZibF5ookr8-HaH3VQq1ToYJqRqbjE2fXcuW3MudlXtLB4MPBIPifPcROtjbqVEzlwPf7_xYzkbMBffcP-nh2B2qlUgLWGZ_i6sFUnueCpIbgfKCmj1DpqaG1OvWTsWl_JPg4EiSmg9_dSvUxyuXNt_9nr3-M2fdH7BpU062jb_qh2eIYzPegDj7GAOahyATLYRzuqyGHcZCHcUiyN8cX9CC673_2B08VBWs</recordid><startdate>20151229</startdate><enddate>20151229</enddate><creator>Rasmussen, Camilla Holzmann</creator><creator>Petersen, Dorthe Roenn</creator><creator>Moeller, Jonas Bech</creator><creator>Hansson, Mattias</creator><creator>Dufva, Martin</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20151229</creationdate><title>Collagen Type I Improves the Differentiation of Human Embryonic Stem Cells towards Definitive Endoderm</title><author>Rasmussen, Camilla Holzmann ; Petersen, Dorthe Roenn ; Moeller, Jonas Bech ; Hansson, Mattias ; Dufva, Martin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-ef0bf526504cda9aafcf2b3b61f0c258005bdc7f5b0c72ca9e43db7295a9bf943</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Analysis</topic><topic>Beta cells</topic><topic>Cancer</topic><topic>Cell adhesion & migration</topic><topic>Cell culture</topic><topic>Cell Differentiation</topic><topic>Collagen</topic><topic>Collagen (type I)</topic><topic>Collagen Type I - 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subjects | Analysis Beta cells Cancer Cell adhesion & migration Cell culture Cell Differentiation Collagen Collagen (type I) Collagen Type I - metabolism Degenerative diseases Diabetes mellitus Diabetes therapy Differentiation Embryo cells Embryonic stem cells Embryos Endoderm Endoderm - cytology Extracellular matrix Fibroblasts Fibronectin Fibronectins Gene expression Gene Expression Profiling Growth factors Human Embryonic Stem Cells - cytology Human Embryonic Stem Cells - metabolism Humans Insulin Kinases Kinetics Matrix protein Proteins Stem cell research Stem cells Substrates |
title | Collagen Type I Improves the Differentiation of Human Embryonic Stem Cells towards Definitive Endoderm |
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