Biology subjects

Tang, S. Y.

Publications and source records attributed to Tang, S. Y..

23 records · Page 2Linked to original sources

bioRxiv2022

Single Cell RNA-Sequence Analyses Reveal Uniquely Expressed Genes and Heterogeneous Immune Cell Involvement in the Rat Model of Intervertebral Disc Degeneration

Intervertebral disc (IVD) degeneration is characterized by a loss of cellularity, and changes in cell-mediated activity that drives anatomic changes to IVD structure. In this study, we use single cell RNA-sequencing analysis of cells extracted from the degenerating tissues of the rat IVD following lumbar disc puncture. Two control, uninjured IVDs (L2-3, L3-4) and two degenerated, injured IVDs (L4-5, L5-6) from each animal were examined either at two- and eight-week post-operative time points. The cells from these IVDs were extracted and transcriptionally profiled at a single-cell resolution. Unsupervised cluster analysis revealed the presence of 4 known cell types in both non-degenerative and degenerated IVDs based on previously established gene markers: IVD cells, endothelial cells, myeloid cells, and lymphoid cells. As a majority of cells were associated with the IVD cell cluster, sub-clustering was used to further identify the cell populations of the nucleus pulposus, inner and outer annulus fibrosus. The most notable difference between control and degenerated IVDs was the increase of myeloid and lymphoid cells in degenerated samples at 2- and 8- weeks post-surgery. Differential gene expression analysis revealed multiple distinct cell types from the myeloid and lymphoid lineages, most notably macrophages and B lymphocytes and demonstrated a high degree of immune specificity during degeneration. In addition to the heterogenous infiltrating immune cell populations in the degenerating IVD, the increased number of cells in the AF sub-cluster expressing Ngf and Ngfr, encoding for p75NTR, suggest that NGF signaling may be one of the key mediators of the IVD crosstalk between immune and neuronal cell populations. These findings provide the basis for future work to understand the involvement of select subsets of non-resident cells in IVD degeneration.

cell biology↗

bioRxiv2022

Contrast-enhanced microCT evaluation of degeneration following partial and full width injuries to mouse lumbar intervertebral disc

Study DesignPreclinical animal study ObjectiveEvaluation of the degenerative progression resulting from either a partial- or full- width injury to the mouse lumbar intervertebral disc (IVD) using contrast-enhanced micro-computed tomography and histological analyses. We utilized a lateral-retroperitoneal surgical approach to access the lumbar IVD, and the injuries to the IVD were induced by either incising one side of the annulus fibrosus or puncturing both sides of the annulus fibrosus. The full-width injury caused dramatic reduction in nucleus pulposus hydration and significant degeneration. A partial-width injury produces localized deterioration around the annulus fibrosus that resulted in local tissue remodeling without gross degeneration to the IVD. MethodsFemale C57BL/6J mice of 3-4 months age were used in this study. They were divided into three groups to undergo partial-width, full-width, or sham injuries. The L5/L6 and L6/S1 lumbar IVDs were surgically exposed using a lateral-retroperitoneal approach. The L6/S1 IVDs were injured using either a surgical scalpel (partial-width) or a 33G needle (full-width), with the L5/L6 serving as an internal control. These animals were allowed to recover and then sacrificed at 2-, 4-, or 8-weeks post-surgery. The IVDs were assessed for degeneration using contrast-enhanced microCT (CE{micro}CT) and histological analysis. ResultsThe high-resolution 3D evaluation of the IVD confirmed that the respective injuries localized within one side of the annulus fibrosus or spanned the full width of the IVD. The full-width injury caused deteriorations in the nucleus pulposus after 2 weeks and progressed to significant degeneration at 8 weeks, while the partial width injury caused localized disruptions that remained limited to the annulus fibrosus. ConclusionThe use of CE{micro}CT revealed distinct IVD degeneration profiles resulting from partial- and full- width injuries. The partial width injury may serve as an alternative for IVD degeneration resulting from localized annulus fibrosus injuries in humans.

animal behavior and cognition↗

bioRxiv2020

Sex dependent compensatory mechanisms to preserve blood pressure homeostasis in PGI2 receptor deficient mice

Inhibitors of microsomal prostaglandin E synthase-1 (mPges-1) are in the early phase of clinical development. Deletion of mPges-1 confers analgesia, restrains atherogenesis and fails to accelerate thrombogenesis, while suppressing prostaglandin (PG) E2, but increasing biosynthesis of prostacyclin (PGI2). In hyperlipidemic mice, this last effect represents the dominant mechanism by which mPges-1 deletion restrains thrombogenesis, while suppression of PGE2 accounts for its anti-atherogenic effect. However, the impact of mPges-1 depletion on blood pressure (BP) in this setting remains unknown. To address how differential effects on PGE2 and PGI2 might modulate salt-evoked BP responses in the absence of mPges-1, we generated mice lacking the I prostanoid (Ipr) receptor or mPges-1 on a hyperlipidemic background caused by deletion of the low density lipoprotein receptor (Ldlr KOs). Here, mPges-1 depletion significantly increased the BP response to salt loading in male Ldlr KO mice, whereas, despite the direct vasodilator properties of PGI2, Ipr deletion suppressed it. Furthermore, combined deletion of the Ipr abrogated the exaggerated BP response in male mPges-1 KO mice. Suppression of PGE2 biosynthesis was enough to explain the exaggerated BP response to salt loading by either mPges-1/Ldlr depletion or by an MPGES-1 inhibitor in mice expressing human mPGES-1. However, the lack of a hypertensive response to salt in Ipr-deficient mice was attributable to reactive activation of the atrial natriuretic peptide pathway. Interestingly, these unexpected BP phenotypes were not observed in female mice fed a high salt diet. This is attributable to the protective effect of estrogen in Ldlr KO mice and in Ipr /Ldlr DKOs. Thus, estrogen compensates for a deficiency in PGI2 to maintain BP homeostasis in response to high salt in hyperlipidemic female mice. In males, by contrast, augmented formation of ANP plays a similar compensatory role, restraining hypertension and oxidant stress in the setting of Ipr depletion. Hyperlipidemic males on a high salt diet might be at risk of a hypertensive response to mPGES-1 inhibitors.

pharmacology and toxicology↗

bioRxiv2019

Effects of Standing on Spinal Alignment and Lumbar Intervertebral Discs in Young, Healthy Individuals Determined by Positional Magnetic Resonance Imaging

Traditional diagnostic imaging of the spine is performed in supine, a relatively unloaded position. However, the spine is subjected to complex loading environments in daily activities such as standing. Therefore, we seek to quantify the changes from supine to standing in the spines of young, healthy individuals in standing using a positional MRI system. This is an observational study that examined the changes in the spine and individual intervertebral discs (IVDs) during supine and standing of forty healthy participants (19 males / 21 females) without a history of low back pain. The regional lumbar spinal alignment was measured by the sagittal Cobb angle. Segmental IVD measurements included the segmental Cobb angle, anterior to posterior height (A/P) ratio, and IVD width measured at each L1/L2 - L5/S1 levels. The intra-observer intra-class correlation (ICC) consistency model showed values for measurements ranged from 0.76-0.98. The inter-observer ICC values ranged from 0.68-0.99. The Cobb angle decreased in standing. The L5/S1 segmental Cobb angle decreased in standing. The L2/L3 and L3/L4 A/P ratios increased and the L5/S1 A/P ratio decreased in standing. No differences in IVD width were observed from supine to standing. This study examined the regional lumbar spinal alignment and segmental IVD changes from supine to standing in young, healthy individuals without LBP using pMRI. In developing and validating these measurements, we have also established the normative data for healthy, asymptomatic population that could be useful for other investigations examining how individuals with spinal or IVD pathologies may adapt between supine and standing.

physiology↗

bioRxiv2018

Circadian control of lung inflammation in influenza infection

Influenza is a leading cause of respiratory mortality and morbidity. While inflammation is necessary for fighting infection, a fine balance of anti-viral defense and host tolerance is necessary for recovery. Circadian rhythms have been known to modulate inflammation. However, the importance of diurnal variability in the timing of influenza infection is not well understood. Here we demonstrate that endogenous rhythms influence the cellular response to infection in bronchoalveolar lavage (BAL), the pulmonary transcriptomic profile and lesional histology. This time dependent variability does not reflect alterations in viral replication. Rather, we found that better time-dependent outcomes were associated with a preponderance of NK and NKT cells and lower proportion of monocytes in the lung. Thus, host tolerance, rather than viral burden underlies the diurnal gating of influenza induced lung injury.\n\nSignificance statementOur work demonstrates the importance of circadian rhythms in influenza infection --a condition with significant public health implications. Our findings, which establish the role of the circadian rhythms in maintaining the balance between host tolerance pathways and anti-viral responses confers a new framework for evaluating the relevance of circadian influences on immunity.

immunology↗