Biology subjects

Imdahl, F.

Publications and source records attributed to Imdahl, F..

3 recordsLinked to original sources

bioRxiv2024

Satellite glial cells from adult DRG dedifferentiate in vitro and can be reprogrammed into nociceptor-like neurons

In dorsal root ganglia (DRG), neuronal loss has been reported in patients with neuropathic pain, raising the question of whether the DRG, as part of the peripheral nervous system (PNS), harbor an endogenous cell source for neural repair. We found that adult mouse DRG harbor glial cells that dedifferentiate in vitro into Sox2/Sox10-positive glial progenitor-like cells. Coexpression of the developmental transcription factors Neurog1 and Neurog2 was sufficient to induce both neuronal and glial phenotypes. Nerve growth factor supported the maturation of a subset of neurons into nociceptor-like cells expressing functional TrpA1, TrpV1, and TTX-resistant NaV channels. We report the limitation that we miss factors allowing consistent maturation to the sensory neuron profile. In summary, in the PNS, adult DRG-derived glial cells can acquire neural progenitor-like properties, show bipotent reprogramming competence, and may serve as an intrinsic cell source for sensory circuit regeneration.

neuroscience↗

bioRxiv2023

Genetically perturbed myelin as a risk factor for neuroinflammation-driven axon degeneration

Axon degeneration and functional decline in myelin diseases are often attributed to loss of myelin but their relation is not fully understood. Perturbed myelinating glia can instigate chronic neuroinflammation and contribute to demyelination and axonal damage. Here we study mice with distinct defects in the proteolipid protein 1 gene that develop axonal damage which is driven by cytotoxic T cells targeting myelinating oligodendrocytes. We show that persistent ensheathment with perturbed myelin poses a risk for axon degeneration, neuron loss, and behavioral decline. We demonstrate that CD8+ T cell-driven axonal damage is less likely to progress towards degeneration when axons are efficiently demyelinated by activated microglia. Mechanistically, we show that cytotoxic T cell effector molecules induce cytoskeletal alterations within myelinating glia and aberrant actomyosin constriction of axons at paranodal domains. Our study identifies detrimental axon-glia-immune interactions which promote neurodegeneration and possible therapeutic targets for disorders associated with myelin defects and neuroinflammation.

neuroscience↗

bioRxiv2021

Vector-borne Trypanosoma brucei parasites develop in artificial human skin and persist as skin tissue forms

Transmission of Trypanosoma brucei by tsetse flies involves the deposition of the cell cycle-arrested metacyclic life cycle stage into mammalian skin at the site of the flys bite. In the skin, the metacyclic parasites reactivate and differentiate into proliferative trypanosomes before colonizing the hosts blood and tissues. We generated an advanced human skin equivalent and used tsetse flies to naturally infect the artificial skin with trypanosomes. We detailed the chronological order of the parasites development in the skin, and found a rapid activation of metacyclic trypanosomes and differentiation to proliferative parasites. Single-cell parasite transcriptomics were used to document the biological events during differentiation and host invasion at five different timepoints. After the establishment of a proliferative trypanosome population in the skin, the parasites entered a reversible quiescent state characterized by slow replication and a strongly reduced metabolism. We termed these quiescent trypanosomes skin tissue forms (STF), a parasite population that may play an important role in maintaining the infection over long time periods and in asymptomatic infected individuals.

microbiology↗