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Título:
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Modulating Glypican4 suppresses tumorigenicity of embryonic stem cells while preserving self-renewal and pluripotency
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Autor/a:
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Fico, Annalisa; Chevigny, Antoine De; Egea Navarro, Joaquim; Bösl, Michael R.; Cremer, Harold; Maina, Flavio; Dono, Rosanna
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Notas:
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Self-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. |
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Materia(s):
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-Stem Cells
-Self-renewal and differentiation
-Glypicans as signaling modulators |
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Derechos:
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(c) Wiley, 2012
info:eu-repo/semantics/restrictedAccess |
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Tipo de documento:
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article
publishedVersion |
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Editor:
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Wiley
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Compartir:
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