| 1. |
- Kvastad, Linda, et al.
(author)
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The spatial RNA integrity number assay for in situ evaluation of transcriptome quality
- 2021
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In: Communications Biology. - : Springer Nature. - 2399-3642. ; 4:1
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Journal article (peer-reviewed)abstract
- The RNA integrity number (RIN) is a frequently used quality metric to assess the completeness of rRNA, as a proxy for the corresponding mRNA in a tissue. Current methods operate at bulk resolution and provide a single average estimate for the whole sample. Spatial transcriptomics technologies have emerged and shown their value by placing gene expression into a tissue context, resulting in transcriptional information from all tissue regions. Thus, the ability to estimate RNA quality in situ has become of utmost importance to overcome the limitation with a bulk rRNA measurement. Here we show a new tool, the spatial RNA integrity number (sRIN) assay, to assess the rRNA completeness in a tissue wide manner at cellular resolution. We demonstrate the use of sRIN to identify spatial variation in tissue quality prior to more comprehensive spatial transcriptomics workflows. Kvastad et al. develop the spatial RNA Integrity Number (sRIN) assay that evaluates the RNA integrity at cellular resolution. This method improves the resolution of a similar method called the RNA Integrity Number (RIN), demonstrating spatial variation in the quality of RNA samples.
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| 2. |
- Santopolo, Giuseppe, et al.
(author)
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Blocking Notch-Signaling Increases Neurogenesis in the Striatum after Stroke
- 2020
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In: Cells. - : MDPI AG. - 2073-4409. ; 9:7
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Journal article (peer-reviewed)abstract
- Stroke triggers neurogenesis in the striatum in mice, with new neurons deriving in part from the nearby subventricular zone and in part from parenchymal astrocytes. The initiation of neurogenesis by astrocytes within the striatum is triggered by reduced Notch-signaling, and blocking this signaling pathway by deletion of the gene encoding the obligate Notch coactivator Rbpj is sufficient to activate neurogenesis by striatal astrocytes in the absence of an injury. Here we report that blocking Notch-signaling in stroke increases the neurogenic response to stroke 3.5-fold in mice. Deletion of Rbpj results in the recruitment of a larger number of parenchymal astrocytes to neurogenesis and over larger areas of the striatum. These data suggest inhibition of Notch-signaling as a potential translational strategy to promote neuronal regeneration after stroke.
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| 3. |
- Magnusson, Jens, et al.
(author)
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Pattern Recognition with Neuromorphic Sensor System
- 2018
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Reports (other academic/artistic)abstract
- Biological sensor systems are remarkably robust and power efficient systems that solve complex pattern recognition problems. Neuromorphic engineering concerns the design of very-large-scale-integration (VLSI) systems with power-efficient analog circuits that mimic biological sensors and neural systems. In this work, we examine how dynamical models of spiking neural networks (SNNs) and the low-power neuromorphic processor Dynap-se, developed at iniLabs in Zurich, can be used in a pattern-recognition application. We implement and investigate a training protocol for signal classification with an SNN-model incorporating the same neuron- and synapse models as those implemented in Dynap-se. We use the model to classify sampled vibration signals generated in healthy- and faulty states of a wind turbine. We investigate two different methods for conversion of an analog signal to spikes, a software delta-modulator and a neuromorphic sensor system known as the Dynamic Audio Sensor (DAS) from iniLabs. The SNN-based classifier is tested on 10 pairs of healthy- and faulty signals not included in the training set. We achieve 90% classification test accuracy using the delta-modulator. The SNN-based classifier is trained on a rather small dataset. Larger training and test sets are needed to increase the performance and reliability of the results. For the delta-modulator stimuli, the model needs to be further evaluated using for instance cross-validation. For the DAS-stimuli, the classifier is not functioning well in its current state. Possibly, this can be improved by modifying the network architecture. A prototype training protocol for Monte Carlo-based synaptic configuration of Dynap-se is developed using a hardware-in-the-loop approach. The protocol enables optimization of a given cost function, and thus has potential to be further developed for the optimization of neural networks implemented in Dynap-se.
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| 4. |
- Magnusson, Jens
(author)
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Astrocytes : a reservoir for new neurons
- 2017
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Doctoral thesis (other academic/artistic)abstract
- The goal of regenerative medicine is to be able to help the body to replace worn-out cells and tissues. To achieve this goal, one approach being pursued today is to recruit and boost the body’s own mechanisms for cell replacement. In the brain, this approach is perhaps more challenging than in many other organs because the brain’s own ability to replace neurons is almost non-existent. Therefore, an alternative strategy is to genetically reprogram support cells in the living brain directly into neurons, or into progenitor cells which in turn would produce neurons. For such a strategy to work, a first step is to identify a cell type in the brain that has the capacity to act as a source for neurons. This thesis describes work that shows for the first time that astrocytes, one of the most abundant cell types in the brain, can generate neurons in vivo under certain circumstances and in certain brain regions. Thus, astrocytes represent a potential reservoir for new neurons, whose neurogenic capacity might be recruited to improve brain repair. In Paper I, we describe the finding that some astrocytes generate neurons in response to stroke in the striatum of mice. We found that the neurogenic capacity of these astrocytes was under control of the Notch signaling pathway. By manipulating this pathway experimentally, we could activate the neurogenic program of these astrocytes even in the absence of stroke. Yet, not all astrocytes generated neurons. In fact, outside the striatum, most of them did not do so, neither after stroke nor after Notch manipulation. In Paper II, we therefore used single-cell RNA sequencing to better understand how astrocytes respond to Notch manipulation and why this does not induce all astrocytes to undergo neurogenesis. We found that even astrocytes that do not generate neurons in fact initiate early steps of neurogenesis. However, they halt their lineage progression immediately before undergoing transit-amplifying divisions. In the striatum, exposure to a mitogen pushed such halted astrocytes into transit-amplifying divisions, and our results suggest that similar strategies could work also outside the striatum, given the right stimulus. In Paper III, we asked whether stroke-induced striatal neurogenesis occurs also in humans. For this, we used radiocarbon dating to assess the age of striatal neurons isolated from postmortem samples of stroke patients. We found that the stroke-injured striatum contains a higher proportion of young neurons than the non-injured striatum of the same subjects. This could be explained either by neurogenesis or selective death of old neurons. Each of these possibilities would represent an interesting and previously undescribed biological scenario. The work in these three papers suggests that endogenous brain cells exist whose neurogenic properties could be recruited to improve brain repair. However, one additional challenge with neuronal replacement strategies is that the great diversity of neurons in the brain is still incompletely characterized. Before any cell replacement interventions can be undertaken, the cell composition in the healthy brain must be known. In Paper IV, we describe a new method for performing RNA sequencing on intact tissue sections with retained spatial information. This technique, dubbed spatial transcriptomics, is useful for answering fundamental biological questions about cell distribution and gene expression. In addition, it could provide valuable information for disease diagnostics. In summary, the work presented in this thesis provides information that may prove crucial for bringing neuronal replacement strategies closer to the clinic.
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| 5. |
- Ståhl, Patrik, Dr., et al.
(author)
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Visualization and analysis of gene expression in tissue sections by spatial transcriptomics
- 2016
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In: Science. - : AMER ASSOC ADVANCEMENT SCIENCE. - 0036-8075 .- 1095-9203. ; 353:6294, s. 78-82
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Journal article (peer-reviewed)abstract
- Analysis of the pattern of proteins or messenger RNAs (mRNAs) in histological tissue sections is a cornerstone in biomedical research and diagnostics. This typically involves the visualization of a few proteins or expressed genes at a time. We have devised a strategy, which we call "spatial transcriptomics," that allows visualization and quantitative analysis of the transcriptome with spatial resolution in individual tissue sections. By positioning histological sections on arrayed reverse transcription primers with unique positional barcodes, we demonstrate high-quality RNA-sequencing data with maintained two-dimensional positional information from the mouse brain and human breast cancer. Spatial transcriptomics provides quantitative gene expression data and visualization of the distribution of mRNAs within tissue sections and enables novel types of bioinformatics analyses, valuable in research and diagnostics.
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| 6. |
- Magnusson, Jens P, et al.
(author)
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A latent neurogenic program in astrocytes regulated by Notch signaling in the mouse.
- 2014
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In: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 346:6206, s. 237-241
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Journal article (peer-reviewed)abstract
- Neurogenesis is restricted in the adult mammalian brain; most neurons are neither exchanged during normal life nor replaced in pathological situations. We report that stroke elicits a latent neurogenic program in striatal astrocytes in mice. Notch1 signaling is reduced in astrocytes after stroke, and attenuated Notch1 signaling is necessary for neurogenesis by striatal astrocytes. Blocking Notch signaling triggers astrocytes in the striatum and the medial cortex to enter a neurogenic program, even in the absence of stroke, resulting in 850 ± 210 (mean ± SEM) new neurons in a mouse striatum. Thus, under Notch signaling regulation, astrocytes in the adult mouse brain parenchyma carry a latent neurogenic program that may potentially be useful for neuronal replacement strategies.
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| 7. |
- Magnusson, Simon
(author)
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Än gäller pamparnas promenad
- 2014
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In: Språktidningen. - 1654-5028. ; :5, s. 16-22
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Journal article (pop. science, debate, etc.)
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