Modulating Glypican4 suppresses tumorigenicity of embryonic stem cells while preserving self-renewal and pluripotency

Simple item page
dc.contributor.authorFico, Annalisa
dc.contributor.authorChevigny, Antoine De
dc.contributor.authorEgea Navarro, Joaquim
dc.contributor.authorBösl, Michael R.
dc.contributor.authorCremer, Harold
dc.contributor.authorMaina, Flavio
dc.contributor.authorDono, Rosanna
dc.date.accessioned2016-05-23T09:32:46Z
dc.date.embargoEndDate2025-01-01
dc.date.issued2012
dc.description.abstractSelf-renewal and differentiation of stem cell depend on a dynamic interplay of cell-extrinsic and -intrinsic regulators. However, how stem cells perceive the right amount of signal and at the right time to undergo a precise developmental program remains poorly understood. The cell surface proteins Glypicans act as gatekeepers of environmental signals to modulate their perception by target cells. Here, we show that one of these, Glypican4 (Gpc4), is specifically required to maintain the self-renewal potential of mouse embryonic stem cells (ESCs) and to fine tune cell lineage commitment. Notably, Gpc4-mutant ESCs contribute to all embryonic cell lineages when injected in blastocyts but lose their intrinsic tumorigenic properties after implantation into nude mice. Therefore, our molecular and functional studies reveal that Gpc4 maintains distinct stemness features. Moreover, we provide evidence that self-renewal and lineage commitment of different stem cell types is fine tuned by Gpc4 activity by showing that Gpc4 is required for the maintenance of adult neural stem cell fate in vivo. Mechanistically, Gpc4 regulates self-renewal of ESCs by modulating Wnt/b-catenin signaling activities. Thus, our findings establish that Gpc4 acts at the interface of extrinsic and intrinsic signal regulation to fine tune stem cell fate. Moreover, the ability to uncouple pluripotent stem cell differentiation from tumorigenic potential makes Gpc4 as a promising target for cell-based regenerative therapies.ca_ES
dc.identifier.doihttps://doi.org/10.1002/stem.1165
dc.identifier.idgrec018109
dc.identifier.issn1066-5099
dc.identifier.urihttp://hdl.handle.net/10459.1/57083
dc.language.isoengca_ES
dc.publisherWileyca_ES
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.1002/stem.1165ca_ES
dc.relation.ispartofStem Cells, 2012, vol. 30, núm 9, p. 1863-1874ca_ES
dc.rights(c) Wiley, 2012ca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccessca_ES
dc.subjectStem Cellsca_ES
dc.subjectSelf-renewal and differentiationca_ES
dc.subjectGlypicans as signaling modulatorsca_ES
dc.titleModulating Glypican4 suppresses tumorigenicity of embryonic stem cells while preserving self-renewal and pluripotencyca_ES
dc.typearticleca_ES
dc.type.versionpublishedVersionca_ES
Files
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Articles publicats (Ciències Mèdiques Bàsiques)
Articles publicats (IRBLleida)