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1.
Nature ; 626(8001): 1056-1065, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38122823

RESUMEN

The temporal lobe of the human brain contains the entorhinal cortex (EC). This region of the brain is a highly interconnected integrative hub for sensory and spatial information; it also has a key role in episodic memory formation and is the main source of cortical hippocampal inputs1-4. The human EC continues to develop during childhood5, but neurogenesis and neuronal migration to the EC are widely considered to be complete by birth. Here we show that the human temporal lobe contains many young neurons migrating into the postnatal EC and adjacent regions, with a large tangential stream persisting until the age of around one year and radial dispersal continuing until around two to three years of age. By contrast, we found no equivalent postnatal migration in rhesus macaques (Macaca mulatta). Immunostaining and single-nucleus RNA sequencing of ganglionic eminence germinal zones, the EC stream and the postnatal EC revealed that most migrating cells in the EC stream are derived from the caudal ganglionic eminence and become LAMP5+RELN+ inhibitory interneurons. These late-arriving interneurons could continue to shape the processing of sensory and spatial information well into postnatal life, when children are actively interacting with their environment. The EC is one of the first regions of the brain to be affected in Alzheimer's disease, and previous work has linked cognitive decline to the loss of LAMP5+RELN+ cells6,7. Our investigation reveals that many of these cells arrive in the EC through a major postnatal migratory stream in early childhood.


Asunto(s)
Movimiento Celular , Neuronas , Lóbulo Temporal , Animales , Preescolar , Humanos , Lactante , Corteza Entorrinal/citología , Corteza Entorrinal/fisiología , Eminencia Ganglionar/citología , Interneuronas/citología , Interneuronas/fisiología , Macaca mulatta , Neuronas/citología , Neuronas/fisiología , Análisis de Expresión Génica de una Sola Célula , Lóbulo Temporal/citología , Lóbulo Temporal/crecimiento & desarrollo
2.
Nat Aging ; 3(3): 327-345, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-37118429

RESUMEN

Aging is a complex process involving transcriptomic changes associated with deterioration across multiple tissues and organs, including the brain. Recent studies using heterochronic parabiosis have shown that various aspects of aging-associated decline are modifiable or even reversible. To better understand how this occurs, we performed single-cell transcriptomic profiling of young and old mouse brains after parabiosis. For each cell type, we cataloged alterations in gene expression, molecular pathways, transcriptional networks, ligand-receptor interactions and senescence status. Our analyses identified gene signatures, demonstrating that heterochronic parabiosis regulates several hallmarks of aging in a cell-type-specific manner. Brain endothelial cells were found to be especially malleable to this intervention, exhibiting dynamic transcriptional changes that affect vascular structure and function. These findings suggest new strategies for slowing deterioration and driving regeneration in the aging brain through approaches that do not rely on disease-specific mechanisms or actions of individual circulating factors.


Asunto(s)
Células Endoteliales , Transcriptoma , Animales , Ratones , Transcriptoma/genética , Envejecimiento/genética , Parabiosis , Encéfalo
3.
Int J Data Min Bioinform ; 10(3): 329-56, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25946867

RESUMEN

The whole set of human imprinted genes, termed imprintome, is here analysed by means of a reasonable, valid application of the Semantic Web and Linked Data approaches to a few structured datasets in order to provide a comprehensive collection of imprinted genes in the human genome. Thus, we have stored, organised, filtered, and analysed massive amounts of existing data on human imprinted genes towards compiling, structuring and linking data to comprise a sharing resource for genome and epigenome interrogated studies. Our datasets of linked data are the actual research outcome of this human imprintome analysis because as genomics become more and more data intensive, due to huge amounts of biological data, so does our needs for more structured data to be easier mined and shared. We present the resulting first version of the Linked Human Imprintome as a project within Linked Open Data (LOD) initiative (http://lod-cloud.net/) through Data Hub (http:// thedatahub.org/en/dataset/a-draft-version-of-the-linked-human-imprintome).


Asunto(s)
Biología Computacional/métodos , Impresión Genómica , Genómica/métodos , Acceso a la Información , Algoritmos , Islas de CpG , Bases de Datos Factuales , Epigenómica , Perfilación de la Expresión Génica , Genoma Humano , Humanos , Seudogenes , Semántica , Programas Informáticos
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