Studies
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Neural stem cells (NSCs) in the adult brain transit from the quiescent state to proliferation to produce new neurons. The mechanisms regulating this transition in freely behaving animals are, however, poorly understood. We customized in vivo imaging protocols to follow NSCs for several days up to months, observing their activation kinetics in freely behaving mice. Strikingly, NSC division is more frequent during daylight and is inhibited by darkness-induced melatonin signaling. The inhibition of ...
Submitter: Aditi Methi
Investigation: Transcriptomics
Direct reprogramming based on genetic factors resembles a promising strategy to replace lost cells in degenerative diseases such as Parkinson's disease. For this, we developed a knock‐in mouse line carrying a dual dCas9 transactivator system (dCAM) allowing the conditional in vivo activation of endogenous genes. To enable a translational application, we additionally established an AAV‐based strategy carrying intein‐split‐dCas9 in combination with activators (AAV‐dCAS). Both approaches were ...
Submitter: Aditi Methi
Investigation: Transcriptomics
The oligodendrocyte progenitors (OPCs) are at the front of the glial reaction to the traumatic brain injury. However, regulatory pathways steering the OPC reaction as well as the role of reactive OPCs remain largely unknown. Here, we compared a long-lasting, exacerbated reaction of OPCs to the adult zebrafish brain injury with a timely restricted OPC activation to identify the specific molecular mechanisms regulating OPC reactivity and their contribution to regeneration. We demonstrated that the ...
Submitter: Aditi Methi
Investigation: Transcriptomics
Traumatic brain injury leads to a highly orchestrated immune- and glial cell response partially responsible for long-lasting disability and the development of secondary neurodegenerative diseases. A holistic understanding of the mechanisms controlling the responses of specific cell types and their crosstalk is required to develop an efficient strategy for better regeneration. Here, we combine spatial and single-cell transcriptomics to chart the transcriptomic signature of the injured male murine ...
Submitter: Aditi Methi
Investigation: Transcriptomics
Assays: Expression profiling: Spatial Transcriptomics (mouse), Expression profiling: scRNA-seq (mouse)
Astrocytes regulate brain‐wide functions and also show region‐specific differences, but little is known about how general and region‐specific functions are aligned at the single‐cell level. To explore this, we isolated adult mouse diencephalic astrocytes by ACSA‐2‐mediated magnetic‐activated cell sorting (MACS). Single‐cell RNA‐seq revealed 7 gene expression clusters of astrocytes, with 4 forming a supercluster. Within the supercluster, cells differed by gene expression related to ion homeostasis ...
Submitter: Aditi Methi
Investigation: Transcriptomics
Assays: Expression profiling: Bulk RNA-seq (mouse), Expression profiling: scRNA-seq (mouse)
Astrocytes are a viable source for generating new neurons via direct conversion. However, little is known about the neurogenic cascades triggered in astrocytes from different regions of the CNS. Here, we examine the transcriptome induced by the proneural factors Ascl1 and Neurog2 in spinal cord-derived astrocytes in vitro. Each factor initially elicits different neurogenic programs that later converge to a V2 interneuron-like state. Intriguingly, patch sequencing (patch-seq) shows no overall ...
Submitter: Aditi Methi
Investigation: Transcriptomics
Assays: Expression profiling: Bulk RNA-seq (mouse), Expression profiling: scRNA-seq (mouse)
The centrosome acts as the cell’s microtubule organizing center, supporting cell division and the extension of cilia and neurites. Newly born neurons require the microtubule organizing activity of centrosomes to migrate away from their birthplace at the ventricle. O’Neill et al. analyzed the centrosome proteome of human induced pluripotent stem cell–derived neural stem cells and neurons. The neural centrosome proteome contains a variety of RNA-binding/modifying proteins, including an RNA-splicing ...
Submitter: Aditi Methi
Investigation: Transcriptomics