Biology subjects

Jeong, G.

Publications and source records attributed to Jeong, G..

9 recordsLinked to original sources

bioRxiv2025

Aberrant Fibro-Adipogenic Progenitor Subpopulations Drive Volumetric Muscle Loss-Induced Fibrosis

Volumetric muscle loss (VML) injuries result in chronic fibrosis, inflammation, and persistent functional deficits. Fibro-adipogenic progenitor (FAP) cells are a heterogeneous, muscle-resident stromal cell population that play a crucial role in muscle regeneration, but also contribute to fibrosis in muscle disease. The role of FAPs in VML is not well established and may be critical target to ensure functional muscle regeneration after VML. We utilized a VML model in the mouse quadriceps to study the location, secretome, surface marker distribution, gene expression, and single-cell transcriptional profile of FAPs after VML. After VML, a subpopulation of FAPs highly expressed {beta}1-integrin and were elevated in the post-VML muscle tissue; these FAPs had increased fibrotic gene expression and increased myofibroblast differentiation potential. Transforming growth factor-{beta}1 (TGF-{beta}1) and tissue inhibitor of matrix metalloproteinase 1 (TIMP1) were identified as secreted proteins from VML derived FAPs that produced both pro-fibrotic and anti-myogenic signaling. These data establish an aberrant FAP sub-population that are elevated in VML injury and provides novel targets for future scarless muscle regeneration in VML.

pathology↗

bioRxiv2024

Engineering a Cell-Based Orthogonal Ubiquitin Transfer Cascade for Profiling the Substrates of RBR E3 Parkin

The E3 ubiquitin (UB) ligase Parkin utilizes a Ring-Between-Ring (RBR) domain to mediate the transfer of UB to its substrates to regulate diverse cellular functions, including mitochondrial quality control, cell cycle progression, metabolism programming, and the establishment of synaptic functions. Mutations affecting the E3 ligase activity of Parkin are associated with cancer and Parkinsons disease (PD). An essential role of Parkin is to synthesize UB chains on the surface of damaged mitochondria to initiate mitophagy. Still, it is not clear how Parkin carries out other biological functions through the ubiquitination of its downstream targets in the cell. We hypothesized that a comprehensive substrate profile of Parkin would facilitate the discovery of ubiquitination pathways underpinning its multifaceted roles in cell regulation and reveal mechanistic linkages between Parkin malfunction and disease development. Here, we used phage display to assemble an orthogonal ubiquitin transfer (OUT) cascade of Parkin that can exclusively deliver an engineered UB mutant (xUB) to Parkin and its substrates in living cells. We then generated a substrate profile of Parkin by purifying xUB-conjugated proteins from cells and identifying them by proteomics. The OUT screen identified Parkin substrates involved in DNA replication, protein translation, intracellular protein transport, and rhythmic regulation. Based on previous literature implicating alterations in membrane vesicle trafficking in PD, we verified Parkin-catalyzed ubiquitination of Rab GTPases (Rab1a, Rab5a, Rab5c, Rab7a, Rab8a, Rab10, an Rab13) as well as CDK5, with reconstituted ubiquitination reactions in vitro and in cells. We also found chemical-induced stimulation of mitophagy enhanced Parkin-mediated ubiquitination of Rab proteins. These findings demonstrate that the OUT cascade of Parkin can serve as an empowering tool for identifying Parkin substrates to elucidate its cellular functions.

biochemistry↗

bioRxiv2024

Chaperonin-mediated Winter Cold Response via Circadian Clock Components in Arabidopsis

Vernalization and cold acclimation are plant strategies that evolved to enhance their fitness during the winter season. The molecular mechanisms behind these processes in Arabidopsis have been intensively studied. However, how plants measure the duration of long-term cold exposure has not been fully understood. Our research shows that cytosolic chaperonin is crucial for appropriate long-term cold responses by regulating plant circadian clocks. Furthermore, one of the clock components, REVEILLE4 (RVE4) and RVE8 directly activate VERNALIZATION INSENSITIVE 3 (VIN3) and the C-REPEAT BINDING FACTOR (CBF)/DEHYDRATION-RESPONSIVE ELEMENT BINDING 1 (DREB1) family genes, which are key regulators of vernalization and cold acclimation, respectively. The activation of the VIN3 and CBF/DREB1 genes was specific to the time of day, indicating that cold exposure during the day is critical for long-term cold responses. Our research delves deeper into understanding the regulatory mechanism governing these two distinct long-term cold responses.

plant biology↗

bioRxiv2022

Adaptation of Dynamics in Default Mode Network Depending on Mental States: the one-to-many dynamic functional connectivity analysis with fMRI

The default mode network is a brain network processing mental states featuring an internal representation of subjective experiences like autobiographical episodic memory retrieval and a resting state. If the default mode network is the common spatial domain processing such mental states, then the temporal domain might present the differences in the mental states. To detect adaptations in dynamics of a single brain network dependent on the mental states it processes, we suggested a novel analysis method called one-to-many dynamic functional connectivity analysis for fMRI. The analysis method assesses the variance in the partial correlations of a center that are time-windowed functional correlations of a brain region (a center) to the rest of the regions in a brain network, then compares the similarities in the directions of their major variance from the same or distinct mental states. We applied one-to-many dynamic functional connectivity analysis to the default mode network and measured the similarity between the major variances of the partial correlations from three autobiographical episodic memory retrieval states and a resting state. If the major direction of the variance is a configuration presenting the mental states of the brain network, we expect to see the high similarity for the same mental states and less similarity for the distinct mental states. To test our hypothesis with the new analysis method, we chose a single subject who is a late blind with advanced mental imagery ability. The results showed that the dynamic adaption in the default mode network in the two mental states could be well depicted when the posterior cingulate cortex is the center in this single case. Furthermore, we could observe that the weight of the correlation between the posterior cingulate cortex and the right parahippocampal cortex varied mostly and therefore its contribution to the dynamic adaptation was relatively higher than the other correlations.

neuroscience↗

bioRxiv2021

Comparison of neuromuscular junction dynamics following ischemic and aged skeletal muscle

Both aging and neuromuscular diseases lead to significant changes in the morphology and functionality of the neuromuscular synapse. Skeletal muscles display a remarkable regenerative capacity, however, are still susceptible to diseases of aging and peripheral nerve perturbations. In this study, we assessed how neuromuscular synapses differ in aged and injured skeletal muscle using an improved neuromuscular junction (NMJ) staining and imaging method. We found that both aged and ischemic skeletal muscle display Wallerian degeneration of the presynaptic motor axons and fragmentation of postsynaptic acetylcholine receptors (AChRs). Quantifiable measurements of various metrics of the NMJs provide a more concrete idea of the dynamics that are occurring in the muscle microenvironment. We questioned whether neuronal degradation precedes myofiber atrophy or vice versa. Previously, it was shown that a cellular crosstalk exists among the motor neurons, myofibers, vasculature, and mitochondria within the muscle microdomain. It is apparent that lack of blood flow to motor neurons in ischemic skeletal muscle disrupts the structure of NMJs, however it is unclear if the aging condition experiences similar dynamics. We demonstrated that both aged and ischemic skeletal muscle demonstrate similar patterns of degeneration, characterized by a smaller percentage overlap of presynaptic and postsynaptic sides, greater fragmentation of AChRs, and a smaller area of AChR clusters. Together, these results reveal high resolution, precise parallels between the aged and ischemic NMJs. Impact StatementThe goal of this study was to assess changes in presynaptic motor neurons and postsynaptic acetylcholine receptors following an ischemic injury model and compare this with an aging model. This was accomplished by characterizing key components of NMJ morphology, including overlap and size of the receptors. There is currently limited research investigating the cellular communication between skeletal muscle fibers and motor neurons. Additionally, there is limited work comparing neuromuscular remodeling in aged and young models. With the substantial prevalence of neuromuscular disorders, especially in the aging population, it is essential to understand nerve-muscle interactions in order to promote increased mobility and improved quality of life in both injury and aging models.

neuroscience↗

bioRxiv2021

Vernalization-triggered expression of the antisense transcript COOLAIR is mediated by CBF genes

To synchronize flowering time with spring, many plants undergo vernalization, a floral-promotion process triggered by exposure to long-term winter cold. In Arabidopsis thaliana, this is achieved through cold-mediated epigenetic silencing of the floral repressor, FLOWERING LOCUS C (FLC). COOLAIR, a cold-induced antisense RNA transcribed from the FLC locus, has been proposed to facilitate FLC silencing. Here, we show that C-repeat (CRT)/dehydration-responsive elements (DREs) at the 3'-end of FLC and CRT/DRE-binding factors (CBFs) are required for cold-mediated expression of COOLAIR. CBFs bind to CRT/DREs at the 3'-end of FLC, both in vitro and in vivo, and CBF levels increase gradually during vernalization. Cold-induced COOLAIR expression is severely impaired in cbfs mutants in which all CBF genes are knocked-out. Conversely, CBF-overexpressing plants show increased COOLAIR levels even at warm temperatures. We show that COOLAIR is induced by CBFs during early stages of vernalization but COOLAIR levels decrease in later phases as FLC chromatin transitions to an inactive state to which CBFs can no longer bind. We also demonstrate that cbfs and FLC{Delta}COOLAIR mutants exhibit a normal vernalization response despite their inability to activate COOLAIR expression during cold, revealing that COOLAIR is not required for the vernalization process.

plant biology↗

bioRxiv2020

Targeted mutagenesis of the Arabidopsis GROWTH-REGULATING FACTOR (GRF) gene family suggests competition of multiplexed sgRNAs for Cas9 apoprotein

Genome editing in plants typically relies on T-DNA plasmids that are mobilized by Agrobacterium-mediated transformation to deliver the CRISPR/Cas9 machinery. Here, we introduce a series of CRISPR/Cas9 T-DNA vectors for minimal lab settings, such as in the classroom or citizen science projects. Spacer sequences targeting genes of interest can be inserted as annealed short oligonucleotides in a single straightforward cloning step. Fluorescent markers expressed in mature seeds enable reliable selection of transgenic as well as transgene-free individuals using a combination of inexpensive LED lamps and colored-glass alternative filters. Testing these tools on the Arabidopsis GROWTH-REGULATING FACTOR (GRF) gene family, we found that Cas9 expression from an EGG CELL1 (EC1) promoter resulted in tenfold lower mutation rates than expression from a UBIQUITIN10 (UBQ10) promoter. A collection of bona fide null mutations in all nine GRF genes could be established with little effort. Finally, we explored the effects of simultaneously targeting two, four and eight GRF genes on the rate of induced mutations at each target locus. Multiplexing caused strong interference effects: while mutation rates at some loci remained consistently high, mutation rates at other loci dropped dramatically with increasing number of single guide RNA species. Our results suggest potential detrimental genetic interaction between induced mutations as well as competition of CRISPR RNAs for a limiting amount of Cas9 apoprotein.

plant biology↗

bioRxiv2020

Regenerating motor neurons prime muscle stem cells for myogenesis by enhancing protein synthesis and mitochondrial bioenergetics

Throughout life, skeletal muscle, the arbiter of voluntary movements, is maintained by a population of skeletal muscle-dedicated stem cells, called muscle satellite cells (MuSCs). Similar to other adult stem cells, the function of MuSCs is tightly coordinated by the cellular and acellular components of their microenvironment, or the niche. While the processes that control the coupling of neurotransmission and muscle contraction have been well characterized, little is known on the reciprocal crosstalk between neural cells and MuSCs within the muscle microenvironment. Here, we report that mild peripheral nerve injury enhances MuSC myogenic function and muscle regeneration by synergistically augmenting MuSC mitochondrial bioenergetics and upregulating anabolic protein synthesis pathways. We also demonstrate that chronic disruption or degeneration of neuromuscular synapses, such as in muscular dystrophy and biological aging, abolishes MuSC and motor neuron interactions, causing significant deficits in muscle regeneration following injury. These results underscore the importance of neuromuscular junction and neural network as an essential niche of MuSCs. Determining the significance of MuSC-nerve interactions and their functional outcomes, as well as the possibility of modulating these connections, have important implications for our understanding of neuromuscular disease pathology and development of therapeutic interventions. HighlightsO_LIMild peripheral nerve injury increases muscle stem cell bioavailability of healthy muscle. C_LIO_LINerve perturbation stimulates myogenesis by enhancing protein synthesis and mitochondrial metabolism in young, healthy muscle. C_LIO_LISynergistic crosstalk within neuromuscular niche boosts muscle regeneration in young, healthy muscle. C_LIO_LIPositive influences from the neural network on muscle stem cells are abolished in pathological denervation manifested in dystrophic and aging muscle. C_LI

cell biology↗

bioRxiv2018

Chimpanzees but not orangutans display aversive reactions toward their partner receiving a superior reward

Fairness judgment is a fundamental aspect of human cooperation. By carefully balancing the payoffs and efforts with cooperating partner (s) we could either avoid or punish cheaters and stably maintain cooperation. Recent studies investigating the origin of this fairness sentiment have demonstrated that this psychological trait is not unique to humans, but also can be observed in other group-living primates, such as chimpanzees and capuchins, suggesting a convergent evolution of a sense of fairness, with cooperative social life being the selective pressure for it. The current study was designed to test this hypothesis by directly comparing the response to the outcome inequity in two of our closest living relatives, chimpanzees and orangutans, having different social systems, i.e. solitary and patrilocal multi-male multi-female groups. Unlike other inequity experiments, we used a prosocial choice apparatus with different reward distributions (advantageous / disadvantageous) to give subjects an active role of not-sharing foods if they considered it unfair. In addition to the choice, we also recorded the behavioral responses of the apes to the inequity. Throughout the experiments aversive emotional responses toward the disadvantageous inequity were only found in chimpanzees, but not in orangutans, supporting the convergent (or domain-specific) evolution of a sense of fairness. However, this aversion to the inequity did not lead the chimpanzees to actually make selfish choices, indirectly supporting the previous findings that chimpanzees employ a partner choice strategy rather than a punishment for fair cooperation. We also found that hierarchy seems to play an important role in the expression of aversion to inequity and prosocial tendency in chimpanzees.

animal behavior and cognition↗