Polycomb protein eed is required for neurogenesis and cortical injury activation in the subventricular zone

The postnatal subventricular zone (SVZ) harbors neural stem cells (NSCs) that exhibit robust neurogenesis. However, the epigenetic mechanisms that maintain NSCs and regulate neurogenesis remain unclear. We report that label-retaining SVZ NSCs express Eed, the core component of Polycomb repressive co...

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Main Authors: Sun, B, Chang, E, Gerhartl, A, Szele, F
Format: Journal article
Language:English
Published: Oxford University Press 2018
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author Sun, B
Chang, E
Gerhartl, A
Szele, F
author_facet Sun, B
Chang, E
Gerhartl, A
Szele, F
author_sort Sun, B
collection OXFORD
description The postnatal subventricular zone (SVZ) harbors neural stem cells (NSCs) that exhibit robust neurogenesis. However, the epigenetic mechanisms that maintain NSCs and regulate neurogenesis remain unclear. We report that label-retaining SVZ NSCs express Eed, the core component of Polycomb repressive complex 2. In vivo and in vitro conditional knockout and knockdown show Eed is necessary for maintaining NSC proliferation, neurogenesis and neurosphere formation. We discovered that Eed functions to maintain p21 protein levels in NSCs by repressing Gata6 transcription. Both Gata6 overexpression and p21 knockdown reduced neurogenesis, while Gata6 knockdown or p21 overexpression partially rescued neurogenesis after Eed loss. Furthermore, genetic deletion of Eed impaired injury induced SVZ proliferation and emigration. These data reveal a novel epigenetic regulated pathway and suggest an essential role for Eed in SVZ homeostasis and injury.
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spelling oxford-uuid:a675502a-2a72-4417-9abb-a63ca73e53a02022-03-27T02:47:35ZPolycomb protein eed is required for neurogenesis and cortical injury activation in the subventricular zoneJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a675502a-2a72-4417-9abb-a63ca73e53a0EnglishSymplectic Elements at OxfordOxford University Press2018Sun, BChang, EGerhartl, ASzele, FThe postnatal subventricular zone (SVZ) harbors neural stem cells (NSCs) that exhibit robust neurogenesis. However, the epigenetic mechanisms that maintain NSCs and regulate neurogenesis remain unclear. We report that label-retaining SVZ NSCs express Eed, the core component of Polycomb repressive complex 2. In vivo and in vitro conditional knockout and knockdown show Eed is necessary for maintaining NSC proliferation, neurogenesis and neurosphere formation. We discovered that Eed functions to maintain p21 protein levels in NSCs by repressing Gata6 transcription. Both Gata6 overexpression and p21 knockdown reduced neurogenesis, while Gata6 knockdown or p21 overexpression partially rescued neurogenesis after Eed loss. Furthermore, genetic deletion of Eed impaired injury induced SVZ proliferation and emigration. These data reveal a novel epigenetic regulated pathway and suggest an essential role for Eed in SVZ homeostasis and injury.
spellingShingle Sun, B
Chang, E
Gerhartl, A
Szele, F
Polycomb protein eed is required for neurogenesis and cortical injury activation in the subventricular zone
title Polycomb protein eed is required for neurogenesis and cortical injury activation in the subventricular zone
title_full Polycomb protein eed is required for neurogenesis and cortical injury activation in the subventricular zone
title_fullStr Polycomb protein eed is required for neurogenesis and cortical injury activation in the subventricular zone
title_full_unstemmed Polycomb protein eed is required for neurogenesis and cortical injury activation in the subventricular zone
title_short Polycomb protein eed is required for neurogenesis and cortical injury activation in the subventricular zone
title_sort polycomb protein eed is required for neurogenesis and cortical injury activation in the subventricular zone
work_keys_str_mv AT sunb polycombproteineedisrequiredforneurogenesisandcorticalinjuryactivationinthesubventricularzone
AT change polycombproteineedisrequiredforneurogenesisandcorticalinjuryactivationinthesubventricularzone
AT gerhartla polycombproteineedisrequiredforneurogenesisandcorticalinjuryactivationinthesubventricularzone
AT szelef polycombproteineedisrequiredforneurogenesisandcorticalinjuryactivationinthesubventricularzone