BCL7A ‐containing SWI/SNF/BAF complexes modulate mitochondrial bioenergetics during neural progenitor differentiation
| Autor: | Lena Wischhof, Hang‐Mao Lee, Janine Tutas, Clemens Overkott, Eileen Tedt, Miriam Stork, Michael Peitz, Oliver Brüstle, Thomas Ulas, Kristian Händler, Joachim L Schultze, Dan Ehninger, Pierluigi Nicotera, Paolo Salomoni, Daniele Bano |
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| Rok vydání: | 2022 |
| Předmět: |
BCL7A
mitochondrial OXPHOS neural progenitor cells (NPCs) General Biochemistry Genetics and Molecular Biology SWI/SNF/BAF complex Mice Neural Stem Cells ddc:570 Animals metabolism [Transcription Factors] cytology [Neural Stem Cells] Molecular Biology cognitive function Adenosine Triphosphatases General Immunology and Microbiology General Neuroscience Microfilament Proteins metabolism [Microfilament Proteins] Cell Differentiation genetics [Transcription Factors] Chromatin Assembly and Disassembly metabolism [Mitochondria] Mitochondria metabolism [Adenosine Triphosphatases] Energy Metabolism Transcription Factors |
| Zdroj: | The EMBO journal 41(23), e110595 (2022). doi:10.15252/embj.2022110595 |
| ISSN: | 1460-2075 0261-4189 |
| DOI: | 10.15252/embj.2022110595 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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