Journal Article

DZNE-2022-01626

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png BCL7A-containing SWI/SNF/BAF complexes modulate mitochondrial bioenergetics during neural progenitor differentiation.

Wischhof, L. (First author)DZNE* ; Lee, H.-m.DZNE* ; Tutas, J.DZNE* ; Overkott, C.DZNE* ; Tedt, E.DZNE* ; Stork, M.DZNE* ; Peitz, M.Extern* ; Brüstle, O.Extern* ; Ulas, T.DZNE* ; Händler, K.DZNE* ; Schultze, J. L.DZNE* ; Ehninger, D.DZNE* ; Nicotera, P.DZNE* ; Salomoni, P.DZNE* ; Bano, D. (Last author)DZNE*

2022
Wiley Hoboken, NJ [u.a.]

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Please use a persistent id in citations: doi:10.15252/embj.2022110595

Abstract: Mammalian SWI/SNF/BAF chromatin remodeling complexes influence cell lineage determination. While the contribution of these complexes to neural progenitor cell (NPC) proliferation and differentiation has been reported, little is known about the transcriptional profiles that determine neurogenesis or gliogenesis. Here, we report that BCL7A is a modulator of the SWI/SNF/BAF complex that stimulates the genome-wide occupancy of the ATPase subunit BRG1. We demonstrate that BCL7A is dispensable for SWI/SNF/BAF complex integrity, whereas it is essential to regulate Notch/Wnt pathway signaling and mitochondrial bioenergetics in differentiating NPCs. Pharmacological stimulation of Wnt signaling restores mitochondrial respiration and attenuates the defective neurogenic patterns observed in NPCs lacking BCL7A. Consistently, treatment with an enhancer of mitochondrial biogenesis, pioglitazone, partially restores mitochondrial respiration and stimulates neuronal differentiation of BCL7A-deficient NPCs. Using conditional BCL7A knockout mice, we reveal that BCL7A expression in NPCs and postmitotic neurons is required for neuronal plasticity and supports behavioral and cognitive performance. Together, our findings define the specific contribution of BCL7A-containing SWI/SNF/BAF complexes to mitochondria-driven NPC commitment, thereby providing a better understanding of the cell-intrinsic transcriptional processes that connect metabolism, neuronal morphogenesis, and cognitive flexibility.

Keyword(s): Animals (MeSH) ; Mice (MeSH) ; Adenosine Triphosphatases: metabolism (MeSH) ; Chromatin Assembly and Disassembly (MeSH) ; Energy Metabolism (MeSH) ; Mitochondria: metabolism (MeSH) ; Transcription Factors: genetics (MeSH) ; Transcription Factors: metabolism (MeSH) ; Microfilament Proteins: metabolism (MeSH) ; Neural Stem Cells: cytology (MeSH) ; Cell Differentiation (MeSH) ; BCL7A ; SWI/SNF/BAF complex ; cognitive function ; mitochondrial OXPHOS ; neural progenitor cells (NPCs)

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Contributing Institute(s):

1. Aging and Neurodegeneration (AG Bano)
2. Nuclear Function in CNS Pathophysiology (AG Salomoni)
3. Clinical Single Cell Omics (CSCO) / Systems Medicine (AG Schultze)
4. Translational Biogerontology (AG Ehninger)
5. Platform for Single Cell Genomics and Epigenomics (PRECISE)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)
2. 352 - Disease Mechanisms (POF4-352) (POF4-352)
3. 354 - Disease Prevention and Healthy Aging (POF4-354) (POF4-354)

Experiment(s):

1. Platform for Single Cell Genomics and Epigenomics at DZNE University of Bonn

Appears in the scientific report 2022

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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Linked articles:

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Journal Article (Erratum/Correction) Wischhof, L. (First author)DZNE* ; Lee, H.-m.DZNE* ; Tutas, J.DZNE* ; Overkott, C. F.DZNE* ; Tedt, E.DZNE* ; Stork, M.DZNE* ; Peitz, M. ; Brüstle, O. ; Ulas, T.DZNE* ; Händler, K.DZNE* ; Schultze, J. L.DZNE* ; Ehninger, D.DZNE* ; Nicotera, P.DZNE* ; Salomoni, P.DZNE* ; Bano, D. (Last author)DZNE*
Author Correction: BCL7A-containing SWI/SNF/BAF complexes modulate mitochondrial bioenergetics during neural progenitor differentiation.
The EMBO journal 43(19), 4437 - 4438 (2024) [10.1038/s44318-024-00157-7]2024   Files  Fulltext by Pubmed Central BibTeX | EndNote: XML, Text | RIS

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