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Article ; Online: Neuroepigenetic disorders: progress, promises and challenges.

Barco, Angel

2014 Volume 80, Page(s) 1–2

MeSH term(s)	Animals ; Brain/drug effects ; Brain/metabolism ; Chromatin/drug effects ; Chromatin/metabolism ; Chromatin Assembly and Disassembly/drug effects ; DNA Methylation/drug effects ; Epigenesis, Genetic/drug effects ; Epigenomics/methods ; Epigenomics/trends ; Histones/metabolism ; Humans ; Nerve Tissue Proteins/metabolism ; Nervous System Diseases/drug therapy ; Nervous System Diseases/metabolism ; Neurobiology/methods ; Neurobiology/trends ; Neurons/drug effects ; Neurons/metabolism ; Neuropharmacology/methods ; Neuropharmacology/trends ; Protein Processing, Post-Translational/drug effects
Chemical Substances	Chromatin ; Histones ; Nerve Tissue Proteins
Language	English
Publishing date	2014-05
Publishing country	England
Document type	Editorial ; Introductory Journal Article
ZDB-ID	218272-5
ISSN	1873-7064 ; 0028-3908
ISSN (online)	1873-7064
ISSN	0028-3908
DOI	10.1016/j.neuropharm.2014.02.013
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Article: A Novel Classification of Endometriosis Based on Clusters of Comorbidities.

Sarria-Santamera, Antonio / Yemenkhan, Yerden / Terzic, Milan / Ortega, Miguel A / Asunsolo Del Barco, Angel

Biomedicines

2023 Volume 11, Issue 9

Abstract: Endometriosis is a heterogeneous, complex, and still challenging disease, due to its epidemiological, etiological and pathogenic, diagnostic, therapeutic, and prognosis characteristics. The classification of endometriosis is contentious, and existing ... ...

Abstract	Endometriosis is a heterogeneous, complex, and still challenging disease, due to its epidemiological, etiological and pathogenic, diagnostic, therapeutic, and prognosis characteristics. The classification of endometriosis is contentious, and existing therapies show significant variability in their effectiveness. This study aims to capture and describe clusters of women with endometriosis based on their comorbidity. With data extracted from electronic records of primary care, this study performs a hierarchical clustering with the Ward method of women with endometriosis with a subsequent analysis of the distribution of comorbidities. Data were available for 4055 women with endometriosis, and six clusters of women were identified: cluster 1 (less comorbidity), cluster 2 (anxiety and musculoskeletal disorders), cluster 3 (type 1 allergy or immediate hypersensitivity); cluster 4 (multiple morbidities); cluster 5 (anemia and infertility); and cluster 6 (headache and migraine). Clustering aggregates similar units into similar clusters, partitioning dissimilar objects into other clusters at a progressively finer granularity-in this case, groups of women with similarities in their comorbidities. Clusters may provide a deeper insight into the multidimensionality of endometriosis and may represent diverse "endometriosis trajectories" which may be associated with specific molecular and biochemical mechanisms. Comorbidity-based clusters may be important to the scientific study of endometriosis, contributing to the clarification of its clinical complexity and variability. An awareness of those comorbidities may help elucidate the etiopathogenesis and facilitate the accurate earlier diagnosis and initiation of treatments targeted toward particular subgroups.
Language	English
Publishing date	2023-09-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines11092448
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Article ; Online: Transcriptome and epigenome analysis of engram cells: Next-generation sequencing technologies in memory research.

Fuentes-Ramos, Miguel / Alaiz-Noya, Marta / Barco, Angel

Neuroscience and biobehavioral reviews

2021 Volume 127, Page(s) 865–875

Abstract: Transcription and epigenetic changes are integral components of the neuronal response to stimulation and have been postulated to be drivers or substrates for enduring changes in animal behavior, including learning and memory. Memories are thought to be ... ...

Abstract	Transcription and epigenetic changes are integral components of the neuronal response to stimulation and have been postulated to be drivers or substrates for enduring changes in animal behavior, including learning and memory. Memories are thought to be deposited in neuronal assemblies called engrams, i.e., groups of cells that undergo persistent physical or chemical changes during learning and are selectively reactivated to retrieve the memory. Despite the research progress made in recent years, the identity of specific epigenetic changes, if any, that occur in these cells and subsequently contribute to the persistence of memory traces remains unknown. The analysis of these changes is challenging due to the difficulty of exploring molecular alterations that only occur in a relatively small percentage of cells embedded in a complex tissue. In this review, we discuss the recent advances in this field and the promise of next-generation sequencing (NGS) and epigenome editing methods for overcoming these challenges and address long-standing questions concerning the role of epigenetic mechanisms in memory encoding, maintenance and expression.
MeSH term(s)	Animals ; Epigenome ; High-Throughput Nucleotide Sequencing ; Learning ; Neurons ; Transcriptome
Language	English
Publishing date	2021-06-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	282464-4
ISSN	1873-7528 ; 0149-7634
ISSN (online)	1873-7528
ISSN	0149-7634
DOI	10.1016/j.neubiorev.2021.06.010
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Article ; Online: Contribution of spurious transcription to intellectual disability disorders.

Scandaglia, Marilyn / Barco, Angel

Journal of medical genetics

2019 Volume 56, Issue 8, Page(s) 491–498

Abstract: During the development of multicellular organisms, chromatin-modifying enzymes orchestrate the establishment of gene expression programmes that characterise each differentiated cell type. These enzymes also contribute to the maintenance of cell type- ... ...

Abstract	During the development of multicellular organisms, chromatin-modifying enzymes orchestrate the establishment of gene expression programmes that characterise each differentiated cell type. These enzymes also contribute to the maintenance of cell type-specific transcription profiles throughout life. But what happens when epigenomic regulation goes awry? Genomic screens in experimental models of intellectual disability disorders (IDDs) caused by mutations in epigenetic machinery-encoding genes have shown that transcriptional dysregulation constitutes a hallmark of these conditions. Here, we underscore the connections between a subset of chromatin-linked IDDs and spurious transcription in brain cells. We also propose that aberrant gene expression in neurons, including both the ectopic transcription of non-neuronal genes and the activation of cryptic promoters, may importantly contribute to the pathoaetiology of these disorders.
MeSH term(s)	Chromatin/genetics ; Chromatin/metabolism ; Chromatin Assembly and Disassembly ; DNA Methylation ; Ectopic Gene Expression ; Epigenesis, Genetic ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genomic Instability ; Histones/metabolism ; Humans ; Intellectual Disability/diagnosis ; Intellectual Disability/genetics ; Intellectual Disability/metabolism ; Methylation ; Mutation ; Neurons/metabolism ; Transcription, Genetic
Chemical Substances	Chromatin ; Histones
Language	English
Publishing date	2019-02-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	220881-7
ISSN	1468-6244 ; 0022-2593
ISSN (online)	1468-6244
ISSN	0022-2593
DOI	10.1136/jmedgenet-2018-105668
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Article ; Online: Editorial on the Special Issue: Molecules and Cognition.

Barco, Angel / Knafo, Shira

Neuroscience

2017 Volume 370, Page(s) 1–3

MeSH term(s)	Animals ; Brain/metabolism ; Cognition/physiology ; Humans
Language	English
Publishing date	2017-11-04
Publishing country	United States
Document type	Editorial ; Introductory Journal Article
ZDB-ID	196739-3
ISSN	1873-7544 ; 0306-4522
ISSN (online)	1873-7544
ISSN	0306-4522
DOI	10.1016/j.neuroscience.2017.11.003
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Article ; Online: Impact of environmental conditions and chemicals on the neuronal epigenome.

Del Blanco, Beatriz / Barco, Angel

Current opinion in chemical biology

2018 Volume 45, Page(s) 157–165

Abstract: During development, chromatin changes contribute to establishing and maintaining the distinct gene-expression profiles of each individual cell type in a multicellular organism. This feat is especially remarkable in the human brain considering the sheer ... ...

Abstract	During development, chromatin changes contribute to establishing and maintaining the distinct gene-expression profiles of each individual cell type in a multicellular organism. This feat is especially remarkable in the human brain considering the sheer number of distinct cell types that make up this organ. This epigenetic programing is sensitive to environmental influences such as the presence of toxicants, diet, temperature, maternal behavior and many other external factors that can lead to sustained differences in neuronal gene expression. Here, we review a number of studies that demonstrate the existence of these environmental fingerprints in the neuronal epigenome and discuss the current challenges and prospects of environmental neuroepigenetics research.
MeSH term(s)	Animals ; Brain/drug effects ; Brain/metabolism ; Chromatin/genetics ; DNA Methylation/drug effects ; Diet ; Environmental Exposure/adverse effects ; Environmental Exposure/analysis ; Environmental Pollutants/adverse effects ; Environmental Pollutants/toxicity ; Epigenesis, Genetic/drug effects ; Female ; Humans ; Maternal Exposure/adverse effects ; Neurons/drug effects ; Neurons/metabolism ; Pregnancy ; Prenatal Exposure Delayed Effects/chemically induced ; Prenatal Exposure Delayed Effects/genetics
Chemical Substances	Chromatin ; Environmental Pollutants
Language	English
Publishing date	2018-06-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1439176-4
ISSN	1879-0402 ; 1367-5931
ISSN (online)	1879-0402
ISSN	1367-5931
DOI	10.1016/j.cbpa.2018.06.003
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Article ; Online: Kdm1a safeguards the topological boundaries of PRC2-repressed genes and prevents aging-related euchromatinization in neurons.

Del Blanco, Beatriz / Niñerola, Sergio / Martín-González, Ana M / Paraíso-Luna, Juan / Kim, Minji / Muñoz-Viana, Rafael / Racovac, Carina / Sanchez-Mut, Jose V / Ruan, Yijun / Barco, Ángel

Nature communications

2024 Volume 15, Issue 1, Page(s) 1781

Abstract: Kdm1a is a histone demethylase linked to intellectual disability with essential roles during gastrulation and the terminal differentiation of specialized cell types, including neurons, that remains highly expressed in the adult brain. To explore Kdm1a's ... ...

Abstract	Kdm1a is a histone demethylase linked to intellectual disability with essential roles during gastrulation and the terminal differentiation of specialized cell types, including neurons, that remains highly expressed in the adult brain. To explore Kdm1a's function in adult neurons, we develop inducible and forebrain-restricted Kdm1a knockouts. By applying multi-omic transcriptome, epigenome and chromatin conformation data, combined with super-resolution microscopy, we find that Kdm1a elimination causes the neuronal activation of nonneuronal genes that are silenced by the polycomb repressor complex and interspersed with active genes. Functional assays demonstrate that the N-terminus of Kdm1a contains an intrinsically disordered region that is essential to segregate Kdm1a-repressed genes from the neighboring active chromatin environment. Finally, we show that the segregation of Kdm1a-target genes is weakened in neurons during natural aging, underscoring the role of Kdm1a safeguarding neuronal genome organization and gene silencing throughout life.
MeSH term(s)	Histone Demethylases/genetics ; Histone Demethylases/metabolism ; Chromatin/genetics ; Neurons/metabolism
Chemical Substances	Histone Demethylases (EC 1.14.11.-) ; Chromatin
Language	English
Publishing date	2024-03-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-45773-3
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Article ; Online: CBP and p300 Jointly Maintain Neural Progenitor Viability but Play Unique Roles in the Differentiation of Neural Lineages.

González-Martínez, Rocío / Márquez-Galera, Angel / Del Blanco, Beatriz / López-Atalaya, Jose P / Barco, Angel / Herrera, Eloísa

Cells

2022 Volume 11, Issue 24

Abstract: 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 ... ...

Abstract	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.
Language	English
Publishing date	2022-12-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11244118
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Article: Diagnosis of Endometriosis Based on Comorbidities: A Machine Learning Approach.

Tore, Ulan / Abilgazym, Aibek / Asunsolo-Del-Barco, Angel / Terzic, Milan / Yemenkhan, Yerden / Zollanvari, Amin / Sarria-Santamera, Antonio

Biomedicines

2023 Volume 11, Issue 11

Abstract: Endometriosis is defined as the presence of estrogen-dependent endometrial-like tissue outside the uterine cavity. Despite extensive research, endometriosis is still an enigmatic disease and is challenging to diagnose and treat. A common clinical finding ...

Abstract	Endometriosis is defined as the presence of estrogen-dependent endometrial-like tissue outside the uterine cavity. Despite extensive research, endometriosis is still an enigmatic disease and is challenging to diagnose and treat. A common clinical finding is the association of endometriosis with multiple diseases. We use a total of 627,566 clinically collected data from cases of endometriosis (0.82%) and controls (99.18%) to construct and evaluate predictive models. We develop a machine learning platform to construct diagnostic tools for endometriosis. The platform consists of logistic regression, decision tree, random forest, AdaBoost, and XGBoost for prediction, and uses Shapley Additive Explanation (SHAP) values to quantify the importance of features. In the model selection phase, the constructed XGBoost model performs better than other algorithms while achieving an area under the curve (AUC) of 0.725 on the test set during the evaluation phase, resulting in a specificity of 62.9% and a sensitivity of 68.6%. The model leads to a quite low positive predictive value of 1.5%, but a quite satisfactory negative predictive value of 99.58%. Moreover, the feature importance analysis points to age, infertility, uterine fibroids, anxiety, and allergic rhinitis as the top five most important features for predicting endometriosis. Although these results show the feasibility of using machine learning to improve the diagnosis of endometriosis, more research is required to improve the performance of predictive models for the diagnosis of endometriosis. This state of affairs is in part attributed to the complex nature of the condition and, at the same time, the administrative nature of our features. Should more informative features be used, we could possibly achieve a higher AUC for predicting endometriosis. As a result, we merely perceive the constructed predictive model as a tool to provide
Language	English
Publishing date	2023-11-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines11113015
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Article ; Online: Extra centrosomes induce PIDD1-mediated inflammation and immunosurveillance.

Garcia-Carpio, Irmina / Braun, Vincent Z / Weiler, Elias S / Leone, Marina / Niñerola, Sergio / Barco, Angel / Fava, Luca L / Villunger, Andreas

The EMBO journal

2023 Volume 42, Issue 20, Page(s) e113510

Abstract: Unscheduled increases in ploidy underlie defects in tissue function, premature aging, and malignancy. A concomitant event to polyploidization is the amplification of centrosomes, the main microtubule organization centers in animal cells. Supernumerary ... ...

Abstract	Unscheduled increases in ploidy underlie defects in tissue function, premature aging, and malignancy. A concomitant event to polyploidization is the amplification of centrosomes, the main microtubule organization centers in animal cells. Supernumerary centrosomes are frequent in tumors, correlating with higher aggressiveness and poor prognosis. However, extra centrosomes initially also exert an onco-protective effect by activating p53-induced cell cycle arrest. If additional signaling events initiated by centrosomes help prevent pathology is unknown. Here, we report that extra centrosomes, arising during unscheduled polyploidization or aberrant centriole biogenesis, induce activation of NF-κB signaling and sterile inflammation. This signaling requires the NEMO-PIDDosome, a multi-protein complex composed of PIDD1, RIPK1, and NEMO/IKKγ. Remarkably, the presence of supernumerary centrosomes suffices to induce a paracrine chemokine and cytokine profile, able to polarize macrophages into a pro-inflammatory phenotype. Furthermore, extra centrosomes increase the immunogenicity of cancer cells and render them more susceptible to NK-cell attack. Hence, the PIDDosome acts as a dual effector, able to engage not only the p53 network for cell cycle control but also NF-κB signaling to instruct innate immunity.
MeSH term(s)	Animals ; Centrosome/metabolism ; Inflammation/pathology ; Monitoring, Immunologic ; Neoplasms/metabolism ; NF-kappa B/genetics ; NF-kappa B/metabolism ; Tumor Suppressor Protein p53/metabolism ; Humans
Chemical Substances	NF-kappa B ; Tumor Suppressor Protein p53 ; PIDD1 protein, human
Language	English
Publishing date	2023-08-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	586044-1
ISSN	1460-2075 ; 0261-4189
ISSN (online)	1460-2075
ISSN	0261-4189
DOI	10.15252/embj.2023113510
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