Biology subjects

Jenkins, J. E.

Publications and source records attributed to Jenkins, J. E..

3 recordsLinked to original sources

bioRxiv2026

Neuropeptide Signaling Promotes Stem-Cell Driven Regeneration in Planarians

Neurons and neuroendocrine cells produce neuropeptides, which act as long-range signals to modulate organismal state and physiological function. In a few cases, neuropeptides have been thought to promote regeneration, but understanding this connection has been difficult due to the relatively poor regenerative capacity of most traditional model organisms. To test whether neuropeptides drive robust regeneration, we used the highly regenerative asexual planarian flatworm as a model. We began by investigating enzymes that cleave and process pre-propeptides to produce bioactive neuropeptides. We characterized 12 putative neuropeptide-processing enzymes and identified three enzymes, prohormone convertase 2 (pc2), carboxypeptidase E (CPE), and peptidylglycine alpha-hydroxylating monooxygenase (PHM-1) that regulate regeneration through their effects on stem cell differentiation and maintenance. We then investigated 51 of the 52 known neuropeptide-encoding genes in planarians, finding that 16 of these genes promote efficient regeneration and/or stem cell function. Our work indicates that diverse neuropeptides regulate endogenous pluripotent stem cells during homeostasis and in robust regeneration. Our data supports a key role for neuropeptide signaling in planarians to promote a pro-regenerative state, which could be valuable to mimic in regenerative therapies.

neuroscience↗

bioRxiv2022

Heterotrimeric G proteins regulate planarian regeneration and behavior

G protein-coupled receptors (GPCRs) play broad roles in development and stem cell biology, but few roles for GPCR signaling in complex tissue regeneration have been uncovered. Planarian flatworms robustly regenerate all tissues and provide a model with which to explore potential functions for GPCR signaling in somatic regeneration and pluripotent stem cell biology. As a first step toward exploring GPCR function in planarians, we investigated downstream signal transducers that work with GPCRs, called heterotrimeric G proteins. Here, we characterized the complete heterotrimeric G protein complement in Schmidtea mediterranea for the first time and found that seven heterotrimeric G protein subunits promote regeneration. We further characterized two subunits critical for regeneration, Gq1 and G{beta}1-4a, finding that they promote the late phase of anterior polarity re-establishment, likely through anterior pole-produced Follistatin. Incidentally, we also found that five heterotrimeric G proteins modulate planarian behavior. We further identified a putative serotonin receptor, gcr052, that we propose works with G{beta}x2 in planarian locomotion, demonstrating the utility of our strategy for identifying relevant GPCRs. Our work provides foundational insight into roles of heterotrimeric G proteins in planarian biology and serves as a useful springboard towards broadening our understanding of GPCR signaling in adult tissue regeneration.

developmental biology↗

bioRxiv2019

Regional astrocyte interferon-γ signaling regulates immunoproteasome-mediated protection during chronic autoimmunity

In early autoimmune neuroinflammation, interferon (IFN){gamma} and its upregulation of the immunoproteasome (iP) is pathologic. However, during chronic multiple sclerosis (MS), IFN{gamma} has protective properties and, the role of the iP remains to be fully elucidated. Here, we demonstrated that IFN{gamma} signaling in regional astrocytes induces the iP and protects the CNS during autoimmunity. In MS tissue, iP expression was enhanced in spinal cord compared to brainstem lesions, which correlated with a decrease in oxidative stress. In vitro, IFN{gamma} stimulation enhanced iP expression, reduced reactive oxygen species burden, and decreased oxidatively damaged and poly-ubiquitinated protein accumulation preferentially in human spinal cord astrocytes, which was abrogated with the use of the iP inhibitor, ONX 0914. During the chronic phase of an MS animal model, experimental autoimmune encephalomyelitis (EAE), ONX 0914 treatment exacerbated disease and led to increased oxidative stress and poly-ubiquitinated protein build-up. Finally, mice with astrocyte-specific loss of the IFN{gamma} receptor exhibited worsened chronic EAE associated with reduced iP expression, enhanced lesion size and oxidative stress and poly-ubiquitinated protein accumulation in astrocytes. Taken together, our data reveal a protective role for IFN{gamma} in chronic neuroinflammation and identify a novel function of the iP in astrocytes during CNS autoimmunity.

neuroscience↗