The effect of dual inhibition of Ras-MEK-ERK and GSK3β pathways on development of in vitro cultured rabbit embryos
Dual inhibition (2i) of Ras-MEK-ERK and GSK3β pathways enables the derivation of embryo stem cells (ESCs) from refractory mouse strains and, for permissive strains, allows ESC derivation with no external protein factor stimuli involvement. In addition, blocking of ERK signalling in 8-cell-stage mous...
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| Veröffentlicht in: | Zygote (Cambridge) 2020-06, Vol.28 (3), p.183-190 |
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| creator | Bontovics, Babett Maraghechi, Pouneh Lázár, Bence Anand, Mahek Németh, Kinga Fábián, Renáta Vašíček, Jaromír Makarevich, Alexander V Gócza, Elen Chrenek, Peter |
| description | Dual inhibition (2i) of Ras-MEK-ERK and GSK3β pathways enables the derivation of embryo stem cells (ESCs) from refractory mouse strains and, for permissive strains, allows ESC derivation with no external protein factor stimuli involvement. In addition, blocking of ERK signalling in 8-cell-stage mouse embryos leads to ablation of GATA4/6 expression in hypoblasts, suggesting fibroblast growth factor (FGF) dependence of hypoblast formation in the mouse. In human, bovine or porcine embryos, the hypoblast remains unaffected or displays slight-to-moderate reduction in cell number. In this study, we demonstrated that segregation of the hypoblast and the epiblast in rabbit embryos is FGF independent and 2i treatment elicits only a limited reinforcement in favour of OCT4-positive epiblast populations against the GATA4-/6-positive hypoblast population. It has been previously shown that TGFβ/Activin A inhibition overcomes the pervasive differentiation and inhomogeneity of rat iPSCs, rat ESCs and human iPSCs while prompting them to acquire naïve properties. However, TGFβ/Activin A inhibition, alone or together with Rho-associated, coiled-coil containing protein kinase (ROCK) inhibition, was not compatible with the viability of rabbit embryos according to the ultrastructural analysis of preimplantation rabbit embryos by electron microscopy. In rabbit models ovulation upon mating allows the precise timing of progression of the pregnancy. It produces several embryos of the desired stage in one pregnancy and a relatively short gestation period, making the rabbit embryo a suitable model to discover the cellular functions and mechanisms of maintenance of pluripotency in embryonic cells and the embryo-derived stem cells of other mammals. |
| doi_str_mv | 10.1017/S0967199419000753 |
| format | Article |
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In addition, blocking of ERK signalling in 8-cell-stage mouse embryos leads to ablation of GATA4/6 expression in hypoblasts, suggesting fibroblast growth factor (FGF) dependence of hypoblast formation in the mouse. In human, bovine or porcine embryos, the hypoblast remains unaffected or displays slight-to-moderate reduction in cell number. In this study, we demonstrated that segregation of the hypoblast and the epiblast in rabbit embryos is FGF independent and 2i treatment elicits only a limited reinforcement in favour of OCT4-positive epiblast populations against the GATA4-/6-positive hypoblast population. It has been previously shown that TGFβ/Activin A inhibition overcomes the pervasive differentiation and inhomogeneity of rat iPSCs, rat ESCs and human iPSCs while prompting them to acquire naïve properties. However, TGFβ/Activin A inhibition, alone or together with Rho-associated, coiled-coil containing protein kinase (ROCK) inhibition, was not compatible with the viability of rabbit embryos according to the ultrastructural analysis of preimplantation rabbit embryos by electron microscopy. In rabbit models ovulation upon mating allows the precise timing of progression of the pregnancy. It produces several embryos of the desired stage in one pregnancy and a relatively short gestation period, making the rabbit embryo a suitable model to discover the cellular functions and mechanisms of maintenance of pluripotency in embryonic cells and the embryo-derived stem cells of other mammals.</description><identifier>ISSN: 0967-1994</identifier><identifier>EISSN: 1469-8730</identifier><identifier>DOI: 10.1017/S0967199419000753</identifier><identifier>PMID: 32192548</identifier><language>eng</language><publisher>England: Cambridge University Press</publisher><subject>Ablation ; Activin ; Amides - pharmacology ; Animal models ; Animals ; Antibodies ; Benzamides - pharmacology ; Cell number ; Coils ; Derivation ; Diphenylamine - analogs & derivatives ; Diphenylamine - pharmacology ; Electron microscopy ; Embryo Culture Techniques ; Embryo, Mammalian - cytology ; Embryo, Mammalian - embryology ; Embryo, Mammalian - metabolism ; Embryonic Development - drug effects ; Embryos ; Enzyme Inhibitors - pharmacology ; Extracellular signal-regulated kinase ; Female ; Fibroblast growth factors ; Gene expression ; Germ Layers - cytology ; Germ Layers - drug effects ; Germ Layers - metabolism ; Gestation ; Glycogen Synthase Kinase 3 beta - antagonists & inhibitors ; Glycogen Synthase Kinase 3 beta - metabolism ; Growth factors ; Inhibitory postsynaptic potentials ; Inhomogeneity ; Kinases ; Laboratories ; MAP Kinase Signaling System - drug effects ; Mitogen-Activated Protein Kinase Kinases - antagonists & inhibitors ; Mitogen-Activated Protein Kinase Kinases - metabolism ; Oct-4 protein ; Ovulation ; Pluripotency ; Pregnancy ; Protein kinase ; Proteins ; Pyrazoles - pharmacology ; Pyridines - pharmacology ; Pyrimidines - pharmacology ; Rabbits ; Ras protein ; ras Proteins - antagonists & inhibitors ; ras Proteins - metabolism ; Signal transduction ; Stem cell transplantation ; Stem cells ; Thiosemicarbazones - pharmacology</subject><ispartof>Zygote (Cambridge), 2020-06, Vol.28 (3), p.183-190</ispartof><rights>Cambridge University Press 2020</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c244t-1032ffc436ab268f6bf2bdb5566e36d47123ab836f69f46567c532c6ee624a2f3</citedby><cites>FETCH-LOGICAL-c244t-1032ffc436ab268f6bf2bdb5566e36d47123ab836f69f46567c532c6ee624a2f3</cites><orcidid>0000-0001-7720-4720</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27922,27923</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32192548$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bontovics, Babett</creatorcontrib><creatorcontrib>Maraghechi, Pouneh</creatorcontrib><creatorcontrib>Lázár, Bence</creatorcontrib><creatorcontrib>Anand, Mahek</creatorcontrib><creatorcontrib>Németh, Kinga</creatorcontrib><creatorcontrib>Fábián, Renáta</creatorcontrib><creatorcontrib>Vašíček, Jaromír</creatorcontrib><creatorcontrib>Makarevich, Alexander V</creatorcontrib><creatorcontrib>Gócza, Elen</creatorcontrib><creatorcontrib>Chrenek, Peter</creatorcontrib><title>The effect of dual inhibition of Ras-MEK-ERK and GSK3β pathways on development of in vitro cultured rabbit embryos</title><title>Zygote (Cambridge)</title><addtitle>Zygote</addtitle><description>Dual inhibition (2i) of Ras-MEK-ERK and GSK3β pathways enables the derivation of embryo stem cells (ESCs) from refractory mouse strains and, for permissive strains, allows ESC derivation with no external protein factor stimuli involvement. In addition, blocking of ERK signalling in 8-cell-stage mouse embryos leads to ablation of GATA4/6 expression in hypoblasts, suggesting fibroblast growth factor (FGF) dependence of hypoblast formation in the mouse. In human, bovine or porcine embryos, the hypoblast remains unaffected or displays slight-to-moderate reduction in cell number. In this study, we demonstrated that segregation of the hypoblast and the epiblast in rabbit embryos is FGF independent and 2i treatment elicits only a limited reinforcement in favour of OCT4-positive epiblast populations against the GATA4-/6-positive hypoblast population. It has been previously shown that TGFβ/Activin A inhibition overcomes the pervasive differentiation and inhomogeneity of rat iPSCs, rat ESCs and human iPSCs while prompting them to acquire naïve properties. However, TGFβ/Activin A inhibition, alone or together with Rho-associated, coiled-coil containing protein kinase (ROCK) inhibition, was not compatible with the viability of rabbit embryos according to the ultrastructural analysis of preimplantation rabbit embryos by electron microscopy. In rabbit models ovulation upon mating allows the precise timing of progression of the pregnancy. It produces several embryos of the desired stage in one pregnancy and a relatively short gestation period, making the rabbit embryo a suitable model to discover the cellular functions and mechanisms of maintenance of pluripotency in embryonic cells and the embryo-derived stem cells of other mammals.</description><subject>Ablation</subject><subject>Activin</subject><subject>Amides - pharmacology</subject><subject>Animal models</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Benzamides - pharmacology</subject><subject>Cell number</subject><subject>Coils</subject><subject>Derivation</subject><subject>Diphenylamine - analogs & derivatives</subject><subject>Diphenylamine - pharmacology</subject><subject>Electron microscopy</subject><subject>Embryo Culture Techniques</subject><subject>Embryo, Mammalian - cytology</subject><subject>Embryo, Mammalian - embryology</subject><subject>Embryo, Mammalian - metabolism</subject><subject>Embryonic Development - drug effects</subject><subject>Embryos</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Extracellular signal-regulated kinase</subject><subject>Female</subject><subject>Fibroblast growth factors</subject><subject>Gene expression</subject><subject>Germ Layers - cytology</subject><subject>Germ Layers - drug effects</subject><subject>Germ Layers - metabolism</subject><subject>Gestation</subject><subject>Glycogen Synthase Kinase 3 beta - antagonists & inhibitors</subject><subject>Glycogen Synthase Kinase 3 beta - metabolism</subject><subject>Growth factors</subject><subject>Inhibitory postsynaptic potentials</subject><subject>Inhomogeneity</subject><subject>Kinases</subject><subject>Laboratories</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>Mitogen-Activated Protein Kinase Kinases - antagonists & inhibitors</subject><subject>Mitogen-Activated Protein Kinase Kinases - metabolism</subject><subject>Oct-4 protein</subject><subject>Ovulation</subject><subject>Pluripotency</subject><subject>Pregnancy</subject><subject>Protein kinase</subject><subject>Proteins</subject><subject>Pyrazoles - pharmacology</subject><subject>Pyridines - pharmacology</subject><subject>Pyrimidines - pharmacology</subject><subject>Rabbits</subject><subject>Ras protein</subject><subject>ras Proteins - antagonists & inhibitors</subject><subject>ras Proteins - metabolism</subject><subject>Signal transduction</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Thiosemicarbazones - pharmacology</subject><issn>0967-1994</issn><issn>1469-8730</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</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><recordid>eNplkM1Kw0AURgdRbK0-gBsZcB2d_2SWUmqVVoS2rsNMMkNTkkydSSp9LR_EZzKx1Y2rC_ee71z4ALjG6A4jHN8vkRQxlpJhiRCKOT0BQ8yEjJKYolMw7M9Rfx-AixA2PRNLdg4GlGBJOEuGIKzWBhprTdZAZ2HeqhIW9brQRVO4ul8tVIheJrNosphBVedwupzRr0-4Vc36Q-0D7Kjc7EzptpWpfyRFDXdF4x3M2rJpvcmhV7oTQlNpv3fhEpxZVQZzdZwj8PY4WY2fovnr9Hn8MI8ywlgTYUSJtRmjQmkiEiu0JTrXnAthqMhZjAlVOqHCCmmZ4CLOOCWZMEYQpoilI3B78G69e29NaNKNa33dvUwJQ4xwzLjsKHygMu9C8MamW19Uyu9TjNK-5vRfzV3m5mhudWXyv8Rvr_Qb8oR3kA</recordid><startdate>202006</startdate><enddate>202006</enddate><creator>Bontovics, Babett</creator><creator>Maraghechi, Pouneh</creator><creator>Lázár, Bence</creator><creator>Anand, Mahek</creator><creator>Németh, Kinga</creator><creator>Fábián, Renáta</creator><creator>Vašíček, Jaromír</creator><creator>Makarevich, Alexander V</creator><creator>Gócza, Elen</creator><creator>Chrenek, Peter</creator><general>Cambridge University Press</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>3V.</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><orcidid>https://orcid.org/0000-0001-7720-4720</orcidid></search><sort><creationdate>202006</creationdate><title>The effect of dual inhibition of Ras-MEK-ERK and GSK3β pathways on development of in vitro cultured rabbit embryos</title><author>Bontovics, Babett ; Maraghechi, Pouneh ; Lázár, Bence ; Anand, Mahek ; Németh, Kinga ; Fábián, Renáta ; Vašíček, Jaromír ; Makarevich, Alexander V ; Gócza, Elen ; Chrenek, Peter</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c244t-1032ffc436ab268f6bf2bdb5566e36d47123ab836f69f46567c532c6ee624a2f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Ablation</topic><topic>Activin</topic><topic>Amides - pharmacology</topic><topic>Animal models</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Benzamides - pharmacology</topic><topic>Cell number</topic><topic>Coils</topic><topic>Derivation</topic><topic>Diphenylamine - analogs & derivatives</topic><topic>Diphenylamine - pharmacology</topic><topic>Electron microscopy</topic><topic>Embryo Culture Techniques</topic><topic>Embryo, Mammalian - cytology</topic><topic>Embryo, Mammalian - embryology</topic><topic>Embryo, Mammalian - metabolism</topic><topic>Embryonic Development - drug effects</topic><topic>Embryos</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Extracellular signal-regulated kinase</topic><topic>Female</topic><topic>Fibroblast growth factors</topic><topic>Gene expression</topic><topic>Germ Layers - cytology</topic><topic>Germ Layers - drug effects</topic><topic>Germ Layers - metabolism</topic><topic>Gestation</topic><topic>Glycogen Synthase Kinase 3 beta - antagonists & inhibitors</topic><topic>Glycogen Synthase Kinase 3 beta - 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In addition, blocking of ERK signalling in 8-cell-stage mouse embryos leads to ablation of GATA4/6 expression in hypoblasts, suggesting fibroblast growth factor (FGF) dependence of hypoblast formation in the mouse. In human, bovine or porcine embryos, the hypoblast remains unaffected or displays slight-to-moderate reduction in cell number. In this study, we demonstrated that segregation of the hypoblast and the epiblast in rabbit embryos is FGF independent and 2i treatment elicits only a limited reinforcement in favour of OCT4-positive epiblast populations against the GATA4-/6-positive hypoblast population. It has been previously shown that TGFβ/Activin A inhibition overcomes the pervasive differentiation and inhomogeneity of rat iPSCs, rat ESCs and human iPSCs while prompting them to acquire naïve properties. However, TGFβ/Activin A inhibition, alone or together with Rho-associated, coiled-coil containing protein kinase (ROCK) inhibition, was not compatible with the viability of rabbit embryos according to the ultrastructural analysis of preimplantation rabbit embryos by electron microscopy. In rabbit models ovulation upon mating allows the precise timing of progression of the pregnancy. It produces several embryos of the desired stage in one pregnancy and a relatively short gestation period, making the rabbit embryo a suitable model to discover the cellular functions and mechanisms of maintenance of pluripotency in embryonic cells and the embryo-derived stem cells of other mammals.</abstract><cop>England</cop><pub>Cambridge University Press</pub><pmid>32192548</pmid><doi>10.1017/S0967199419000753</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0001-7720-4720</orcidid></addata></record> |
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| ispartof | Zygote (Cambridge), 2020-06, Vol.28 (3), p.183-190 |
| issn | 0967-1994 1469-8730 |
| language | eng |
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| source | MEDLINE; Cambridge Journals |
| subjects | Ablation Activin Amides - pharmacology Animal models Animals Antibodies Benzamides - pharmacology Cell number Coils Derivation Diphenylamine - analogs & derivatives Diphenylamine - pharmacology Electron microscopy Embryo Culture Techniques Embryo, Mammalian - cytology Embryo, Mammalian - embryology Embryo, Mammalian - metabolism Embryonic Development - drug effects Embryos Enzyme Inhibitors - pharmacology Extracellular signal-regulated kinase Female Fibroblast growth factors Gene expression Germ Layers - cytology Germ Layers - drug effects Germ Layers - metabolism Gestation Glycogen Synthase Kinase 3 beta - antagonists & inhibitors Glycogen Synthase Kinase 3 beta - metabolism Growth factors Inhibitory postsynaptic potentials Inhomogeneity Kinases Laboratories MAP Kinase Signaling System - drug effects Mitogen-Activated Protein Kinase Kinases - antagonists & inhibitors Mitogen-Activated Protein Kinase Kinases - metabolism Oct-4 protein Ovulation Pluripotency Pregnancy Protein kinase Proteins Pyrazoles - pharmacology Pyridines - pharmacology Pyrimidines - pharmacology Rabbits Ras protein ras Proteins - antagonists & inhibitors ras Proteins - metabolism Signal transduction Stem cell transplantation Stem cells Thiosemicarbazones - pharmacology |
| title | The effect of dual inhibition of Ras-MEK-ERK and GSK3β pathways on development of in vitro cultured rabbit embryos |
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