Biology subjects

Lee, J. H.

Publications and source records attributed to Lee, J. H..

133 records · Page 8Linked to original sources

bioRxiv2018

Cancer exosomes induce tumor neo-neurogenesis potentiating tumor growth

Patients with densely innervated tumors do worse than those with less innervated cancers. We hypothesize that neural elements are acquired by a tumor-induced process, called neo-neurogenesis. Here, we use PC12 cells in a simple system to test this hypothesis. PC12 cells extend processes, called neurites, only when appropriately stimulated. Using this system, we show that patient tumors release vesicles (exosomes) which induce PC12 neurite outgrowth. Using a cancer mouse model, we show that tumor cells compromised in exosome release grow slower and are less innervated than controls indicating a contribution of innervation to disease progression. We find that neo-neurogenesis is mediated in part by the axonal guidance molecule, EphrinB1, contained in exosomes. These findings support testing EphrinB1 blockers to inhibit tumor innervation and improve survival.\n\nOne Sentence SummaryTumors release exosomes which not only promote their own innervation but also potentiate their growth.

cancer biology↗

bioRxiv2017

Biologically plausible mechanisms underlying motor response correction during reward-based decision-making

AO_SCPLOWBSTRACTC_SCPLOWOur propensity to acclimate to new surroundings and choose a goal-directed behavior for a maximal reward (i.e., optimal outcome) is natural, for it affects our survival. A line of studies suggested that anterior cingulate cortex (ACC) could be a potential hub for adaptive behaviors. For instance, an experimental study noted ACCs contribution to selecting motor responses for maximal rewards; it found 1) that ACC neurons were selectively activated when the reward was reduced and 2) that suppression of ACC activity impaired monkeys ability to change motor responses to obtain the maximal reward. To probe ACC functions in adaptive behaviors, we sought biologically-plausible mechanisms to account for the experimental findings mentioned above by utilizing a computational model. Our simulation results raise the possibility that ACC can correct behavioral responses by reading out and updating the motor plans (guiding future motor responses) stored in prefrontal cortex (PFC).

neuroscience↗

bioRxiv2017

Efficient in situ barcode sequencing using padlock probe-based BaristaSeq

Cellular DNA/RNA tags (barcodes) allow for multiplexed cell lineage tracing and neuronal projection mapping with cellular resolution. Conventional approaches to reading out cellular barcodes trade off spatial resolution with throughput. Bulk sequencing achieves high throughput but sacrifices spatial resolution, whereas manual cell picking has low throughput. In situ sequencing could potentially achieve both high spatial resolution and high throughput, but current in situ sequencing techniques are inefficient at reading out cellular barcodes. Here we describe BaristaSeq, an optimization of a targeted, padlock probe-based technique for in situ barcode sequencing compatible with Illumina sequencing chemistry. BaristaSeq results in a five-fold increase in amplification efficiency, with a sequencing accuracy of at least 97%. BaristaSeq could be used for barcode-assisted lineage tracing, and to map long-range neuronal projections.\n\nKey PointsO_LIIn situ sequencing by gap-filling padlock probes is limited by the strand displacement of DNA polymerases\nC_LIO_LIIllumina sequencing chemistry offers superior signal-to-noise ratio in situ compared to sequencing by ligation\nC_LIO_LIBaristaSeq as an accurate method for barcode sequencing in situ with improved gap-filling efficiency\nC_LI

molecular biology↗

bioRxiv2017

Accurate detection of low-level somatic mutations with technical replication for next-generation sequencing

Accurate genome-wide detection of somatic mutations with low variant allele frequency (VAF, <1%) has proven difficult, for which generalized, scalable methods are lacking. Herein, we describe a new computational method, called RePlow that we developed to detect low-VAF somatic mutations based on simple, library-level replicates for next-generation sequencing on any platform. Through joint analysis of replicates, RePlow is able to remove prevailing background errors in next-generation sequencing analysis, facilitating remarkable improvement in the detection accuracy for low-VAF somatic mutations (up to [~]99% reduction in false positives). The method was validated in independent cancer panel and brain tissue sequencing data. Our study suggests a new paradigm with which to exploit an overwhelming abundance of sequencing data for accurate variant detection.

genomics↗

bioRxiv2017

Cortical circuit based lossless neural integrator for perceptual decision-making

The intrinsic uncertainty of sensory information (i.e., evidence) does not necessarily deter an observer from making a reliable decision. Indeed, uncertainty can be reduced by integrating (accumulating) incoming sensory evidence. It is widely thought that this accumulation is instantiated via recurrent rate-code neural networks. Yet, these networks do not fully explain important aspects of perceptual decision-making, such as a subjects ability to retain accumulated evidence during temporal gaps in the sensory evidence. Here, we utilized computational models to show that cortical circuits can switch flexibly between retention and integration modes during perceptual decision-making. Further, we found that, depending on how the sensory evidence was readout, we could simulate stepping and ramping activity patterns, which may be analogous to those seen in different studies of decision-making in the primate parietal cortex. This finding may reconcile these previous empirical studies because it suggests these two activity patterns emerge from the same mechanism.

neuroscience↗

bioRxiv2017

Multiple reference genome sequences of hot pepper reveal the massive evolution of plant disease resistance genes by retroduplication

Transposable elements (TEs) provide major evolutionary forces leading to new genome structure and species diversification. However, the role of TEs in the expansion of disease resistance gene families has been unexplored in plants. Here, we report high-quality de novo genomes for two peppers (Capsicum baccatum and C. chinense) and an improved reference genome (C. annuum). Dynamic genome rearrangements involving translocations among chromosome 3, 5 and 9 were detected in comparison between C. baccatum and the two other peppers. The amplification of athila LTR-retrotransposons, members of the gypsy superfamily, led to genome expansion in C. baccatum. In-depth genome-wide comparison of genes and repeats unveiled that the copy numbers of NLRs were greatly increased by LTR-retrotransposon-mediated retroduplication. Moreover, retroduplicated NLRs exhibited great abundance across the angiosperms, with most cases lineage-specific and thus recent events. Our study revealed that retroduplication has played key roles in the emergence of new disease-resistance genes in plants.

plant biology↗

bioRxiv2016

Visual processing mode switching regulated by VIP cells

The responses of neurons in mouse primary visual cortex (V1) to visual stimuli depend on behavioral states. Specifically, surround suppression is reduced during locomotion. Although locomotion-induced vasoactive intestinal polypeptide positive (VIP) interneuron depolarization can account for the reduction of surround suppression, the functions of VIP cell depolarization are not fully understood. Here we utilize a firing rate model and a computational model to elucidate the potential functions of VIP cell depolarization during locomotion. Our analyses suggest 1) that surround suppression sharpens the visual responses in V1 to a stationary scene, 2) that depolarized VIP cells enhance V1 responses to moving objects by reducing self-induced surround suppression and 3) that during locomotion V1 neuron responses to some features of the moving objects can be selectively enhanced. Thus, VIP cells regulate surround suppression to allow pyramidal neurons to optimally encode visual information independent of behavioral state.

neuroscience↗