Regulation of Mesodermal Differentiation of Mouse Embryonic Stem Cells by Basement Membranes

Fujiwara, Hironobu; Hayashi, Yoshitaka; Sanzen, Noriko; Kobayashi, Reiko; Weber, Charles N.; Emoto, Tomomi; Futaki, Sugiko; Niwa, Hitoshi; Murray, Patricia; Edgar, David; Sekiguchi, Kiyotoshi

doi:https://doi.org/10.1074/jbc.M611452200

Regulation of Mesodermal Differentiation of Mouse Embryonic Stem Cells by Basement Membranes

Fujiwara, Hironobu; Hayashi, Yoshitaka; Sanzen, Noriko et al.

Journal of Biological Chemistry, 2007, 282(40), 29701-29711

Number of Access:1,003（2025-08-18 12:33 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/71427

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Title	Regulation of Mesodermal Differentiation of Mouse Embryonic Stem Cells by Basement Membranes
Creator	NRID 1000020615744 1000020615744 CreatorName Fujiwara, Hironobu
	NRID 1000080420363 1000080420363 CreatorName Hayashi, Yoshitaka
	CreatorName Sanzen, Noriko
	CreatorName Kobayashi, Reiko
	CreatorName Weber, Charles N.
	CreatorName Emoto, Tomomi
	NRID 1000000403014 1000000403014 CreatorName Futaki, Sugiko
	NRID 1000080253730 1000080253730 CreatorName Niwa, Hitoshi
	CreatorName Murray, Patricia
	CreatorName Edgar, David
	NRID 1000050187845 1000050187845 researchmap permalink read0054833 read0054833 Scopus Author ID 7201662709 7201662709 ORCID 0000-0002-6433-1410 0000-0002-6433-1410 CreatorName Sekiguchi, Kiyotoshi
Description	This research was originally published in the Journal of Biological Chemistry. Hironobu Fujiwara, Yoshitaka Hayashi, Noriko Sanzen, Reiko Kobayashi, Charles N. Weber, Tomomi Emoto, Sugiko Futaki, Hitoshi Niwa, Patricia Murray, David Edgar and Kiyotoshi Sekiguchi. Regulation of Mesodermal Differentiation of Mouse Embryonic Stem Cells by Basement Membranes. J. Biol. Chem. 2007; 282: 29701–29711 © the American Society for Biochemistry and Molecular Biology
Abstract	Basement membranes (BMs) have been implicated in cell fate determination during development. Embryoid bodies (EBs) derived from mouse embryonic stem cells deficient in the laminin γ1 chain are incapable of depositing a BM, resulting in failure of primitive ectoderm epithelialization. To elucidate the mechanisms involved in this phenomenon, we compared the gene expression profiles of EBs with or without a BM to identify the genes showing BM-dependent expression. We found that the expressions of marker genes for the epithelial-mesenchymal transition (EMT), including the transcription factor Snai2, were up-regulated in LAMC1-/- EBs, whereas restoration of a BM to LAMC1-/- EBs suppressed the up-regulation of these genes. Overexpression of Snai2 induced the EMT in control EBs by molecular and morphological criteria, suggesting that suppression of the EMT regulatory genes is involved in BM-dependent epithelialization of primitive ectoderm. Despite the failure of primitive ectoderm epithelialization in BM-deficient EBs, mesodermal differentiation was not compromised, but rather accelerated. Furthermore, at later stages of control EB differentiation, the BM was disrupted at the gastrulation site where mesodermal markers were strongly expressed only in cells that had lost contact with the BM. Taken together, these results indicate that the BM prevents the EMT and precocious differentiation of primitive ectoderm toward mesoderm in EBs, implying that BMs are important for the control of mammalian gastrulation.
Publisher	American Society for Biochemistry and Molecular Biology
Source Title	Journal of Biological Chemistry
Volume (Issue)	282(40)
Page	29701-29711
Date of Issued	2007-10
Language	English
Handle URL	https://hdl.handle.net/11094/71427
eISSN	1083351X
NCID	AA1202441X
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1074/jbc.M611452200
Access Rights	open access
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Journal of Biological Chemistry. 2007, 282(40), p. 29701-29711
DC.title	Regulation of Mesodermal Differentiation of Mouse Embryonic Stem Cells by Basement Membranes
DC.creator	Fujiwara, Hironobu
	Hayashi, Yoshitaka
	Sanzen, Noriko
	Kobayashi, Reiko
	Weber, Charles N.
	Emoto, Tomomi
	Futaki, Sugiko
	Niwa, Hitoshi
	Murray, Patricia
	Edgar, David
	Sekiguchi, Kiyotoshi
DC.publisher	American Society for Biochemistry and Molecular Biology
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2007-10
DC.identifier	https://doi.org/10.1074/jbc.M611452200
DC.description	This research was originally published in the Journal of Biological Chemistry. Hironobu Fujiwara, Yoshitaka Hayashi, Noriko Sanzen, Reiko Kobayashi, Charles N. Weber, Tomomi Emoto, Sugiko Futaki, Hitoshi Niwa, Patricia Murray, David Edgar and Kiyotoshi Sekiguchi. Regulation of Mesodermal Differentiation of Mouse Embryonic Stem Cells by Basement Membranes. J. Biol. Chem. 2007; 282: 29701–29711 © the American Society for Biochemistry and Molecular Biology
DCTERMS.abstract	Basement membranes (BMs) have been implicated in cell fate determination during development. Embryoid bodies (EBs) derived from mouse embryonic stem cells deficient in the laminin γ1 chain are incapable of depositing a BM, resulting in failure of primitive ectoderm epithelialization. To elucidate the mechanisms involved in this phenomenon, we compared the gene expression profiles of EBs with or without a BM to identify the genes showing BM-dependent expression. We found that the expressions of marker genes for the epithelial-mesenchymal transition (EMT), including the transcription factor Snai2, were up-regulated in LAMC1-/- EBs, whereas restoration of a BM to LAMC1-/- EBs suppressed the up-regulation of these genes. Overexpression of Snai2 induced the EMT in control EBs by molecular and morphological criteria, suggesting that suppression of the EMT regulatory genes is involved in BM-dependent epithelialization of primitive ectoderm. Despite the failure of primitive ectoderm epithelialization in BM-deficient EBs, mesodermal differentiation was not compromised, but rather accelerated. Furthermore, at later stages of control EB differentiation, the BM was disrupted at the gastrulation site where mesodermal markers were strongly expressed only in cells that had lost contact with the BM. Taken together, these results indicate that the BM prevents the EMT and precocious differentiation of primitive ectoderm toward mesoderm in EBs, implying that BMs are important for the control of mammalian gastrulation.
DC.format	71427
citation_title	Regulation of Mesodermal Differentiation of Mouse Embryonic Stem Cells by Basement Membranes
citation_author	Fujiwara, Hironobu
	Hayashi, Yoshitaka
	Sanzen, Noriko
	Kobayashi, Reiko
	Weber, Charles N.
	Emoto, Tomomi
	Futaki, Sugiko
	Niwa, Hitoshi
	Murray, Patricia
	Edgar, David
	Sekiguchi, Kiyotoshi
citation_publisher	American Society for Biochemistry and Molecular Biology
citation_language	English
citation_date	2007-10
citation_journal_title	Journal of Biological Chemistry
citation_volume	282
citation_issue	40
citation_firstpage	29701
citation_lastpage	29711
citation_doi	https://doi.org/10.1074/jbc.M611452200
citation_public_url	https://hdl.handle.net/11094/71427

Regulation of Mesodermal Differentiation of Mouse Embryonic Stem Cells by Basement Membranes

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