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Neural Progenitor Cell Gene Expression In Response To CBP(S436A) mutant

ABSTRACT: Neural Progenitor Cell Gene Expression In Response To CBP(S436A) mutant

PROVIDER: PRJNA525137 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8650312.fastq.gz	Fastqsanger.gz
	SRR8650313.fastq.gz	Fastqsanger.gz
	SRR8650314.fastq.gz	Fastqsanger.gz
	SRR8650315.fastq.gz	Fastqsanger.gz

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Neural Progenitor Cell Gene Expression In Response To CBP(S436A) mutant

Project description:The histone acetyltransferase, CREB binding protein (CBP), is important for appropriate differentiation of neural stem/progenitor cells (NPCs). The serine 436 phosphoryaltion in CBP responds to enviormental cues to promote neuronal differentiaiton of adult NPCs (Fatt, et al, Stem Cell Reports, 5:1-8, 2015; Gouveia, et al., Stem Cell Reports, 11: 719-734, 2016). Here, we have used a phospho-null CBPS436A knock-in (KI) mouse strain to isolate subventricular zone (SVZ) NPCs, which were further expanded and differentiated ex vivo for RNAseq analysis. This allowed us to study underlying molecular mechanisms that mediate CBP Ser436 phosphorylation to promote adult NPC differentiation.

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CBP and p300 Jointly Maintain Neural Progenitor Viability but Play Unique Roles in the Differentiation of Neural Lineages

Project description:The paralogous lysine acetyltransferases 3 (KAT3), CBP and P300, play critical roles during neurodevelopment, but their specific roles in neural precursors maintenance and differentiation remain obscure. In fact, it is still unclear whether these proteins are individually or jointly essential in processes such as proliferation of neural precursors, differentiation to specific neural cell types, or both. Here, we use subventricular zone-derived neurospheres as a potential ex vivo developmental model to analyze the proliferation and differentiation of neural stem cells (NSCs) lacking CBP, p300, or both proteins. The results showed that CBP and p300 are not individually essential for maintenance and proliferation of NSCs, although their combined ablation seriously compromised cell division. In turn, the absence of either of the two proteins compromised the differentiation of NSC into the neuronal and astrocytic lineages. Single-nucleus RNA sequencing analysis of neural cell cultures derived from CBP or p300 mutant neurospheres revealed divergent trajectories of neural differentiation upon CBP or p300 ablation, confirming unique functions and nonredundant roles in neural development. These findings contribute to a better understanding of the shared and individual roles of KAT3 proteins in neural differentiation and the etiology of neurodevelopmental disorders caused by their deficiency.

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