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- Lazaridis, I, et al.
(författare)
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A hypothalamus-habenula circuit controls aversion
- 2019
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Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 24:9, s. 1351-1368
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Tidskriftsartikel (refereegranskat)
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- Carlen, M, et al.
(författare)
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Genetic visualization of neurogenesis
- 2006
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Ingår i: Experimental cell research. - : Elsevier BV. - 0014-4827. ; 312:15, s. 2851-2859
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Tidskriftsartikel (refereegranskat)
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- Forsberg, M, et al.
(författare)
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Efficient reprogramming of adult neural stem cells to monocytes by ectopic expression of a single gene
- 2010
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 107:33, s. 14657-14661
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Tidskriftsartikel (refereegranskat)abstract
- Neural stem cells have a broad differentiation repertoire during embryonic development and can be reprogrammed to pluripotency comparatively easily. We report that adult neural stem cells can be reprogrammed at very high efficiency to monocytes, a differentiated fate of an unrelated somatic lineage, by ectopic expression of the Ets transcription factor PU.1. The reprogrammed cells display a marker profile and functional characteristics of monocytes and integrate into tissues after transplantation. The failure to reprogram lineage-committed neural cells to monocytes with PU.1 suggests that neural stem cells are uniquely amenable to reprogramming.
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- Hansson, EM, et al.
(författare)
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Recording Notch signaling in real time
- 2006
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Ingår i: Developmental neuroscience. - : S. Karger AG. - 0378-5866 .- 1421-9859. ; 28:1-2, s. 118-127
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Tidskriftsartikel (refereegranskat)abstract
- Notch signaling is a highly conserved signaling pathway, which is critical for many cell fate decisions. Ligand activation of Notch leads to cleavage of the Notch receptor and liberation of the Notch intracellular domain (ICD) from the membrane-tethered receptor. After translocation to the nucleus, the Notch ICD interacts with the DNA-binding protein CSL to activate gene transcription. To better understand the temporal and spatial aspects of Notch signaling, we here describe a fluorescent protein-based reporter assay that allows Notch activation to be followed in real time in individual cells. We have generated a reporter construct composed of 12 CSL-binding motifs linked to fluorescent proteins with different half-lives: a stabler red fluorescent protein (DsRedExpressDR) and a destabilized form of green fluorescent protein (d1EGFP). The fluorescent reporters reflect the activation status of Notch signaling with single-cell resolution. The reporters rapidly respond to various forms of Notch activation, including ligand activation of full-length Notch receptors. Finally, we use this assay to gain insights into the level of Notch signaling in CNS progenitor cells in culture and in vivo.
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| 20. |
- Lu, S, et al.
(författare)
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Assessing the replicability of spatial gene expression using atlas data from the adult mouse brain
- 2021
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Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1545-7885. ; 19:7, s. e3001341-
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Tidskriftsartikel (refereegranskat)abstract
- High-throughput, spatially resolved gene expression techniques are poised to be transformative across biology by overcoming a central limitation in single-cell biology: the lack of information on relationships that organize the cells into the functional groupings characteristic of tissues in complex multicellular organisms. Spatial expression is particularly interesting in the mammalian brain, which has a highly defined structure, strong spatial constraint in its organization, and detailed multimodal phenotypes for cells and ensembles of cells that can be linked to mesoscale properties such as projection patterns, and from there, to circuits generating behavior. However, as with any type of expression data, cross-dataset benchmarking of spatial data is a crucial first step. Here, we assess the replicability, with reference to canonical brain subdivisions, between the Allen Institute’s in situ hybridization data from the adult mouse brain (Allen Brain Atlas (ABA)) and a similar dataset collected using spatial transcriptomics (ST). With the advent of tractable spatial techniques, for the first time, we are able to benchmark the Allen Institute’s whole-brain, whole-transcriptome spatial expression dataset with a second independent dataset that similarly spans the whole brain and transcriptome. We use regularized linear regression (LASSO), linear regression, and correlation-based feature selection in a supervised learning framework to classify expression samples relative to their assayed location. We show that Allen Reference Atlas labels are classifiable using transcription in both data sets, but that performance is higher in the ABA than in ST. Furthermore, models trained in one dataset and tested in the opposite dataset do not reproduce classification performance bidirectionally. While an identifying expression profile can be found for a given brain area, it does not generalize to the opposite dataset. In general, we found that canonical brain area labels are classifiable in gene expression space within dataset and that our observed performance is not merely reflecting physical distance in the brain. However, we also show that cross-platform classification is not robust. Emerging spatial datasets from the mouse brain will allow further characterization of cross-dataset replicability ultimately providing a valuable reference set for understanding the cell biology of the brain.
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- Meletis, K, et al.
(författare)
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Have the bloody cells gone to our heads?
- 2001
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Ingår i: The Journal of cell biology. - : Rockefeller University Press. - 0021-9525 .- 1540-8140. ; 155:5, s. 699-702
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have shown that cells expressing neuronal antigens can be derived from a bone marrow transplant. A new report lends support to and extends these previous results by presenting compelling morphological evidence for the generation and integration of highly differentiated bone marrow–derived neurons.
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- Ortiz, C, et al.
(författare)
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Spatial Transcriptomics: Molecular Maps of the Mammalian Brain
- 2021
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Ingår i: Annual review of neuroscience. - : Annual Reviews. - 1545-4126 .- 0147-006X. ; 44, s. 547-562
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Tidskriftsartikel (refereegranskat)abstract
- Maps of the nervous system inspire experiments and theories in neuroscience. Advances in molecular biology over the past decades have revolutionized the definition of cell and tissue identity. Spatial transcriptomics has opened up a new era in neuroanatomy, where the unsupervised and unbiased exploration of the molecular signatures of tissue organization will give rise to a new generation of brain maps. We propose that the molecular classification of brain regions on the basis of their gene expression profile can circumvent subjective neuroanatomical definitions and produce common reference frameworks that can incorporate cell types, connectivity, activity, and other modalities. Here we review the technological and conceptual advances made possible by spatial transcriptomics in the context of advancing neuroanatomy and discuss how molecular neuroanatomy can redefine mapping of the nervous system.
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