Glycogen synthase kinase 3 (GSK3) inhibitor, SB-216763, promotes pluripotency in mouse embryonic stem cells
Canonical Wnt/β-catenin signaling has been suggested to promote self-renewal of pluripotent mouse and human embryonic stem cells. Here, we show that SB-216763, a glycogen synthase kinase-3 (GSK3) inhibitor, can maintain mouse embryonic stem cells (mESCs) in a pluripotent state in the absence of exog...
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| Veröffentlicht in: | PloS one 2012-06, Vol.7 (6), p.e39329-e39329 |
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| creator | Kirby, Leslie A Schott, Jason T Noble, Brenda L Mendez, Daniel C Caseley, Paul S Peterson, Sarah C Routledge, Tyler J Patel, Nilay V |
| description | Canonical Wnt/β-catenin signaling has been suggested to promote self-renewal of pluripotent mouse and human embryonic stem cells. Here, we show that SB-216763, a glycogen synthase kinase-3 (GSK3) inhibitor, can maintain mouse embryonic stem cells (mESCs) in a pluripotent state in the absence of exogenous leukemia inhibitory factor (LIF) when cultured on mouse embryonic fibroblasts (MEFs). MESCs maintained with SB-216763 for one month were morphologically indistinguishable from LIF-treated mESCs and expressed pluripotent-specific genes Oct4, Sox2, and Nanog. Furthermore, Nanog immunostaining was more homogenous in SB-216763-treated colonies compared to LIF. Embryoid bodies (EBs) prepared from these mESCs expressed early-stage markers for all three germ layers, and could efficiently differentiate into cardiac-like cells and MAP2-immunoreactive neurons. To our knowledge, SB-216763 is the first GSK3 inhibitor that can promote self-renewal of mESC co-cultured with MEFs for more than two months. |
| doi_str_mv | 10.1371/journal.pone.0039329 |
| format | Article |
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Here, we show that SB-216763, a glycogen synthase kinase-3 (GSK3) inhibitor, can maintain mouse embryonic stem cells (mESCs) in a pluripotent state in the absence of exogenous leukemia inhibitory factor (LIF) when cultured on mouse embryonic fibroblasts (MEFs). MESCs maintained with SB-216763 for one month were morphologically indistinguishable from LIF-treated mESCs and expressed pluripotent-specific genes Oct4, Sox2, and Nanog. Furthermore, Nanog immunostaining was more homogenous in SB-216763-treated colonies compared to LIF. Embryoid bodies (EBs) prepared from these mESCs expressed early-stage markers for all three germ layers, and could efficiently differentiate into cardiac-like cells and MAP2-immunoreactive neurons. To our knowledge, SB-216763 is the first GSK3 inhibitor that can promote self-renewal of mESC co-cultured with MEFs for more than two months.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0039329</identifier><identifier>PMID: 22745733</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; beta Catenin - metabolism ; Biology ; Cell culture ; Cell Differentiation - drug effects ; Cell Line ; Cell self-renewal ; Colonies ; Comparative analysis ; Embryo cells ; Embryo fibroblasts ; Embryonic stem cells ; Embryonic Stem Cells - cytology ; Embryonic Stem Cells - drug effects ; Enzyme inhibitors ; Fibroblasts ; Gene expression ; Glycogen ; Glycogen synthase kinase 3 ; Glycogen Synthase Kinase 3 - antagonists & inhibitors ; Glycogen synthesis ; Heart diseases ; Humans ; Immunohistochemistry ; Indoles - pharmacology ; Inhibitors ; Kinases ; Leukemia ; Leukemia inhibitory factor ; Maleimides - pharmacology ; Metabolism ; Mice ; Neurons - cytology ; Neurons - drug effects ; Oct-4 protein ; Phosphorylation ; Pluripotency ; Polymerase Chain Reaction ; Science ; Signal transduction ; Signaling ; Stem cell transplantation ; Stem cells ; Transcription factors ; Trends ; Tumorigenesis ; Wnt protein ; β-Catenin</subject><ispartof>PloS one, 2012-06, Vol.7 (6), p.e39329-e39329</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Kirby et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://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. 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Here, we show that SB-216763, a glycogen synthase kinase-3 (GSK3) inhibitor, can maintain mouse embryonic stem cells (mESCs) in a pluripotent state in the absence of exogenous leukemia inhibitory factor (LIF) when cultured on mouse embryonic fibroblasts (MEFs). MESCs maintained with SB-216763 for one month were morphologically indistinguishable from LIF-treated mESCs and expressed pluripotent-specific genes Oct4, Sox2, and Nanog. Furthermore, Nanog immunostaining was more homogenous in SB-216763-treated colonies compared to LIF. Embryoid bodies (EBs) prepared from these mESCs expressed early-stage markers for all three germ layers, and could efficiently differentiate into cardiac-like cells and MAP2-immunoreactive neurons. To our knowledge, SB-216763 is the first GSK3 inhibitor that can promote self-renewal of mESC co-cultured with MEFs for more than two months.</description><subject>Animals</subject><subject>beta Catenin - metabolism</subject><subject>Biology</subject><subject>Cell culture</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Line</subject><subject>Cell self-renewal</subject><subject>Colonies</subject><subject>Comparative analysis</subject><subject>Embryo cells</subject><subject>Embryo fibroblasts</subject><subject>Embryonic stem cells</subject><subject>Embryonic Stem Cells - cytology</subject><subject>Embryonic Stem Cells - drug effects</subject><subject>Enzyme inhibitors</subject><subject>Fibroblasts</subject><subject>Gene expression</subject><subject>Glycogen</subject><subject>Glycogen synthase kinase 3</subject><subject>Glycogen Synthase Kinase 3 - antagonists & inhibitors</subject><subject>Glycogen synthesis</subject><subject>Heart diseases</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Indoles - 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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>Kirby, Leslie A</au><au>Schott, Jason T</au><au>Noble, Brenda L</au><au>Mendez, Daniel C</au><au>Caseley, Paul S</au><au>Peterson, Sarah C</au><au>Routledge, Tyler J</au><au>Patel, Nilay V</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Glycogen synthase kinase 3 (GSK3) inhibitor, SB-216763, promotes pluripotency in mouse embryonic stem cells</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-06-26</date><risdate>2012</risdate><volume>7</volume><issue>6</issue><spage>e39329</spage><epage>e39329</epage><pages>e39329-e39329</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Canonical Wnt/β-catenin signaling has been suggested to promote self-renewal of pluripotent mouse and human embryonic stem cells. Here, we show that SB-216763, a glycogen synthase kinase-3 (GSK3) inhibitor, can maintain mouse embryonic stem cells (mESCs) in a pluripotent state in the absence of exogenous leukemia inhibitory factor (LIF) when cultured on mouse embryonic fibroblasts (MEFs). MESCs maintained with SB-216763 for one month were morphologically indistinguishable from LIF-treated mESCs and expressed pluripotent-specific genes Oct4, Sox2, and Nanog. Furthermore, Nanog immunostaining was more homogenous in SB-216763-treated colonies compared to LIF. Embryoid bodies (EBs) prepared from these mESCs expressed early-stage markers for all three germ layers, and could efficiently differentiate into cardiac-like cells and MAP2-immunoreactive neurons. To our knowledge, SB-216763 is the first GSK3 inhibitor that can promote self-renewal of mESC co-cultured with MEFs for more than two months.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22745733</pmid><doi>10.1371/journal.pone.0039329</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Animals beta Catenin - metabolism Biology Cell culture Cell Differentiation - drug effects Cell Line Cell self-renewal Colonies Comparative analysis Embryo cells Embryo fibroblasts Embryonic stem cells Embryonic Stem Cells - cytology Embryonic Stem Cells - drug effects Enzyme inhibitors Fibroblasts Gene expression Glycogen Glycogen synthase kinase 3 Glycogen Synthase Kinase 3 - antagonists & inhibitors Glycogen synthesis Heart diseases Humans Immunohistochemistry Indoles - pharmacology Inhibitors Kinases Leukemia Leukemia inhibitory factor Maleimides - pharmacology Metabolism Mice Neurons - cytology Neurons - drug effects Oct-4 protein Phosphorylation Pluripotency Polymerase Chain Reaction Science Signal transduction Signaling Stem cell transplantation Stem cells Transcription factors Trends Tumorigenesis Wnt protein β-Catenin |
| title | Glycogen synthase kinase 3 (GSK3) inhibitor, SB-216763, promotes pluripotency in mouse embryonic stem cells |
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