TY  - JOUR
AU  - Wischhof, Lena
AU  - Lee, Hang-mao
AU  - Tutas, Janine
AU  - Overkott, Clemens
AU  - Tedt, Eileen
AU  - Stork, Miriam
AU  - Peitz, Michael
AU  - Brüstle, Oliver
AU  - Ulas, Thomas
AU  - Händler, Kristian
AU  - Schultze, Joachim L
AU  - Ehninger, Dan
AU  - Nicotera, Pierluigi
AU  - Salomoni, Paolo
AU  - Bano, Daniele
TI  - BCL7A-containing SWI/SNF/BAF complexes modulate mitochondrial bioenergetics during neural progenitor differentiation.
JO  - The EMBO journal
VL  - 41
IS  - 23
SN  - 0261-4189
CY  - Hoboken, NJ [u.a.]
PB  - Wiley
M1  - DZNE-2022-01626
SP  - e110595
PY  - 2022
AB  - 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.
KW  - Animals
KW  - Mice
KW  - Adenosine Triphosphatases: metabolism
KW  - Chromatin Assembly and Disassembly
KW  - Energy Metabolism
KW  - Mitochondria: metabolism
KW  - Transcription Factors: genetics
KW  - Transcription Factors: metabolism
KW  - Microfilament Proteins: metabolism
KW  - Neural Stem Cells: cytology
KW  - Cell Differentiation
KW  - BCL7A (Other)
KW  - SWI/SNF/BAF complex (Other)
KW  - cognitive function (Other)
KW  - mitochondrial OXPHOS (Other)
KW  - neural progenitor cells (NPCs) (Other)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC9713712
C6  - pmid:36305367
DO  - DOI:10.15252/embj.2022110595
UR  - https://pub.dzne.de/record/165349
ER  -