Transcriptional profiling along the radial axis of CA1 layer of the adult rat hippocampus in the normal and in the epileptic hippocampus.
Full text available in Cell Reports:
Sublayer- and cell-type-specific neurodegenerative transcriptional trajectories in hippocampal sclerosis.
Elena Cid
*
,
Angel Marquez-Galera
*
,
Manuel Valero
,
Beatriz Gal
,
Daniel C Medeiros
,
Carmen M Navarron
,
Luis Ballesteros-Esteban,
Rita Reig-Viader
,
Aixa V Morales
,
Ivan Fernandez-Lamo
,
Daniel Gomez-Dominguez
,
Masaaki Sato
,
Yasunori Hayashi
,
Alex Bayes
,
Angel Barco
,
Jose P Lopez-Atalaya
✉ ,
Liset M de la Prida
✉ .
doi: https://doi.org/10.1016/j.celrep.2021.109229
link: https://www.cell.com/cell-reports/fulltext/S2211-1247(21)00580-5
Associated protocol available in Star Protocols:
A protocol to extract cell-type-specific signatures from differentially expressed genes in bulk-tissue RNA-seq.
Angel Marquez-Galera
✉ ,
Liset M de la Prida
,
Jose P Lopez-Atalaya
✉ .
doi: https://doi.org/10.1016/j.xpro.2022.101121
link: https://star-protocols.cell.com/protocols/1386
Publication related tools:
- Transcriptional profiling along the radial axis of normal and epileptic CA1: http://lopezatalayalab.in.umh-csic.es/CA1_Sublayers_&_Epilepsy
- Single-nuclei transcriptional profiling of normal and epileptic CA1: http://lopezatalayalab.in.umh-csic.es/CA1_SingleNuclei_&_Epilepsy
Web App developed by Angel Marquez-Galera 
, at Lopez-Atalaya Lab.
,
Liset M de la Prida
,
Jose P Lopez-Atalaya
✉ .
doi: https://doi.org/10.1016/j.xpro.2022.101121
link: https://star-protocols.cell.com/protocols/1386
Publication related tools:
- Transcriptional profiling along the radial axis of normal and epileptic CA1: http://lopezatalayalab.in.umh-csic.es/CA1_Sublayers_&_Epilepsy
- Single-nuclei transcriptional profiling of normal and epileptic CA1: http://lopezatalayalab.in.umh-csic.es/CA1_SingleNuclei_&_Epilepsy
Web App developed by Angel Marquez-Galera , at Lopez-Atalaya Lab.
Sublayer profiling in controls (sup/deep)
Sublayer profiling in epilepsy (sup/deep)
Epilepsy effect in deep sublayer (epileptic/control)
Epilepsy effect in superficial sublayer (epileptic/control)
Figure legend:
A, Subpopulation signatures inferred by deconvolution of bulk tissue transcriptome profiles. Gene sets were the top 250 DEGs between superficial and deep CA1 sublayers in epileptic and control rats (as indicated) identified in bulk tissue RNA-seq. For the selected genes, normalized expression was retrieved from publicly available scRNA-seq data from the Allen Brain Map portal (Mouse Whole Cortex and Hippocampus SMART-seq [2019] with 10x-SMART-seq taxonomy [2020]) (Yao et al., 2021), and single cells were summarized by linear dimensionality reduction using principal-component analysis (PCA) (top panels). Cells are colored by population membership (Step 2). Also shown are heatmaps of pairwise correlation for selected gene sets using scRNA-seq data, as indicated above (bottom panels). Bona fide markers of distinct cell types were detected in clusters of highly correlated genes representing cell type gene signatures convoluted in the bulk tissue RNA-seq (Pyr, pyramidal cell; Inter, interneuron; ODC, oligodendrocytes; Astro, astrocytes; Endo, endothelial cells; Micro, microglia; Mural, mural cells). Gene signatures of different types of cells (e.g., Pyrs, Astros, and ODCs) in the deep CA1 sublayer of control and epileptic rats lead to segregation of the cells in the corresponding PCAs and heatmap of the pairwise correlation matrix. Note the different distribution of distinct cell types at the deep and superficial (Sup) sublayers of the CA1 region in control and epileptic rats. Also note the presence of a strong gene signature of Micro in the Sup CA1 sublayer of epileptic rats (arrowhead). Names of highly correlated genes enriched in Micro are shown (Zeisel et al., 2018). B, Similar results were obtained using a different reference dataset from scRNA-seq data (Zeisel et al., 2015).
Image: Extracted from article Figure 3 (A-B).
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This project is lead by the labs of Liset M de la Prida (Instituto Cajal (CSIC), Madrid) and Jose P. Lopez-Atalaya (Instituto de Neurociencias (UMH-CSIC), Alicante). The project is the result of a collaboration between several groups under of the SynCogDis Network of Excellence (http://www.syncogdis.org). Other contributing groups include Àlex Bayés (Institut d'Investigacions Biomèdiques Sant Pau (IIB Sant Pau), Barcelona) and Angel Barco (Instituto de Neurociencias (UMH-CSIC), Alicante). Research Groups |
Hippo-Circuit Lab. (Prida Lab.)
The main goal of our lab is to understand the function of the hippocampal and para-hippocampal circuits in the normal and the epileptic brain. We are interested on how complex patterns of activity are produced with a special emphasis in the cellular and synaptic rules that govern circuit dynamics. To tackle these questions we use different in vivo and in vitro preparations and exploit modern techniques for selective interrogation of neuronal circuits, including cell-type specific opto and chemogenetics. We combine electrophysiological tools with behavioral assessments to relate microcircuit function and dysfunction with cognition. We focus in different forms of activity, including several types of oscillations (ripples, fast ripples, theta and gamma) and epileptiform events.
Recently, we discovered that deep and superficial CA1 pyramidal cells participate differentially during sharp-wave ripples (Valero et al., Nat.Neurosci. 2015). Our data support the idea of a strong regionalization of hippocampal function during basic processes underlying memory consolidation, which is a major research line today in our lab. We next disclosed a mechanism determining firing selectivity and its distorsion in the epileptic hippocampus (Valero et al., Neuron 2017). Our purpose is to better understand the epileptic condition and to identify new therapeutic approaches.
Recently, we discovered that deep and superficial CA1 pyramidal cells participate differentially during sharp-wave ripples (Valero et al., Nat.Neurosci. 2015). Our data support the idea of a strong regionalization of hippocampal function during basic processes underlying memory consolidation, which is a major research line today in our lab. We next disclosed a mechanism determining firing selectivity and its distorsion in the epileptic hippocampus (Valero et al., Neuron 2017). Our purpose is to better understand the epileptic condition and to identify new therapeutic approaches.
Cell Plasticity and Neuropathology Lab. (Lopez-Atalaya Lab.)
Our research focuses on cellular plasticity of microglia and brain macrophages. The ability of a cell to adopt an alternative fate when exposed to different conditions is now emerging as an important process in normal physiology and in disease conditions, such as epilepsy and other neurodegenerative diseases.
In the brain, glial cells play fundamental roles in neuronal physiology including regulation of neurotransmission and synapse formation and maintenance. In addition, neuroglia constitutes the intrinsic brain defense system. Stroke, trauma, infection or chronic neurodegeneration trigger a pronounced glial response. This dual role is associated to a profound phenotypic switch from “basal” to “reactive”. Critically, microglia and other macrophages of the brain, and astrocytes must orchestrate complex genetic programs in response to a variety of stimuli that dictate the induction of alternations in their phenotype to serve the appropriate functions.
We seek to obtain direct mechanistic insights into neuroinflammatory processes. We have particular interest in elucidating the mechanisms underlying the transition between microglia states and maintenance of phenotypic and molecular identity. To do so, we combine mouse genetics, genomics and state-of-the-art histological, cellular and molecular biology methods. Our research may reveal potential targets for novel therapeutics for brain aging and neurodegenerative diseases.
In the brain, glial cells play fundamental roles in neuronal physiology including regulation of neurotransmission and synapse formation and maintenance. In addition, neuroglia constitutes the intrinsic brain defense system. Stroke, trauma, infection or chronic neurodegeneration trigger a pronounced glial response. This dual role is associated to a profound phenotypic switch from “basal” to “reactive”. Critically, microglia and other macrophages of the brain, and astrocytes must orchestrate complex genetic programs in response to a variety of stimuli that dictate the induction of alternations in their phenotype to serve the appropriate functions.
We seek to obtain direct mechanistic insights into neuroinflammatory processes. We have particular interest in elucidating the mechanisms underlying the transition between microglia states and maintenance of phenotypic and molecular identity. To do so, we combine mouse genetics, genomics and state-of-the-art histological, cellular and molecular biology methods. Our research may reveal potential targets for novel therapeutics for brain aging and neurodegenerative diseases.
Web App developed by Angel Marquez-Galera , at Lopez-Atalaya Lab.