CBP and p300 Jointly Maintain Neural Progenitor Viability but Play Unique Roles in the Differentiation of Neural Lineages
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 pro...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-12-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/11/24/4118 |
| _version_ | 1797460978691997696 |
|---|---|
| author | Rocío González-Martínez Angel Márquez-Galera Beatriz Del Blanco Jose P. López-Atalaya Angel Barco Eloísa Herrera |
| author_facet | Rocío González-Martínez Angel Márquez-Galera Beatriz Del Blanco Jose P. López-Atalaya Angel Barco Eloísa Herrera |
| author_sort | Rocío González-Martínez |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T17:12:49Z |
| format | Article |
| id | doaj.art-e65a3a11db6e43a499558b54d008ca51 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T17:12:49Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-e65a3a11db6e43a499558b54d008ca512023-11-24T13:56:10ZengMDPI AGCells2073-44092022-12-011124411810.3390/cells11244118CBP and p300 Jointly Maintain Neural Progenitor Viability but Play Unique Roles in the Differentiation of Neural LineagesRocío González-Martínez0Angel Márquez-Galera1Beatriz Del Blanco2Jose P. López-Atalaya3Angel Barco4Eloísa Herrera5Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas-Universidad Miguel Hernández, CSIC-UMH. Av. Santiago Ramón y Cajal s/n, 03550 Alicante, SpainInstituto de Neurociencias, Consejo Superior de Investigaciones Científicas-Universidad Miguel Hernández, CSIC-UMH. Av. Santiago Ramón y Cajal s/n, 03550 Alicante, SpainInstituto de Neurociencias, Consejo Superior de Investigaciones Científicas-Universidad Miguel Hernández, CSIC-UMH. Av. Santiago Ramón y Cajal s/n, 03550 Alicante, SpainInstituto de Neurociencias, Consejo Superior de Investigaciones Científicas-Universidad Miguel Hernández, CSIC-UMH. Av. Santiago Ramón y Cajal s/n, 03550 Alicante, SpainInstituto de Neurociencias, Consejo Superior de Investigaciones Científicas-Universidad Miguel Hernández, CSIC-UMH. Av. Santiago Ramón y Cajal s/n, 03550 Alicante, SpainInstituto de Neurociencias, Consejo Superior de Investigaciones Científicas-Universidad Miguel Hernández, CSIC-UMH. Av. Santiago Ramón y Cajal s/n, 03550 Alicante, SpainThe 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.https://www.mdpi.com/2073-4409/11/24/4118neuronal differentiationneural progenitor proliferationCBPp300lysine acetylationtranscriptomics |
| spellingShingle | Rocío González-Martínez Angel Márquez-Galera Beatriz Del Blanco Jose P. López-Atalaya Angel Barco Eloísa Herrera CBP and p300 Jointly Maintain Neural Progenitor Viability but Play Unique Roles in the Differentiation of Neural Lineages Cells neuronal differentiation neural progenitor proliferation CBP p300 lysine acetylation transcriptomics |
| title | CBP and p300 Jointly Maintain Neural Progenitor Viability but Play Unique Roles in the Differentiation of Neural Lineages |
| title_full | CBP and p300 Jointly Maintain Neural Progenitor Viability but Play Unique Roles in the Differentiation of Neural Lineages |
| title_fullStr | CBP and p300 Jointly Maintain Neural Progenitor Viability but Play Unique Roles in the Differentiation of Neural Lineages |
| title_full_unstemmed | CBP and p300 Jointly Maintain Neural Progenitor Viability but Play Unique Roles in the Differentiation of Neural Lineages |
| title_short | CBP and p300 Jointly Maintain Neural Progenitor Viability but Play Unique Roles in the Differentiation of Neural Lineages |
| title_sort | cbp and p300 jointly maintain neural progenitor viability but play unique roles in the differentiation of neural lineages |
| topic | neuronal differentiation neural progenitor proliferation CBP p300 lysine acetylation transcriptomics |
| url | https://www.mdpi.com/2073-4409/11/24/4118 |
| work_keys_str_mv | AT rociogonzalezmartinez cbpandp300jointlymaintainneuralprogenitorviabilitybutplayuniquerolesinthedifferentiationofneurallineages AT angelmarquezgalera cbpandp300jointlymaintainneuralprogenitorviabilitybutplayuniquerolesinthedifferentiationofneurallineages AT beatrizdelblanco cbpandp300jointlymaintainneuralprogenitorviabilitybutplayuniquerolesinthedifferentiationofneurallineages AT joseplopezatalaya cbpandp300jointlymaintainneuralprogenitorviabilitybutplayuniquerolesinthedifferentiationofneurallineages AT angelbarco cbpandp300jointlymaintainneuralprogenitorviabilitybutplayuniquerolesinthedifferentiationofneurallineages AT eloisaherrera cbpandp300jointlymaintainneuralprogenitorviabilitybutplayuniquerolesinthedifferentiationofneurallineages |