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Wang, Z.-y.

Publications and source records attributed to Wang, Z.-y..

3 recordsLinked to original sources

A feed-forward loop between niche adenosine and Gzmk⁺ CD8 T cells propagates systemic inflammaging

The causal link between the aging microenvironment and T cell aging remains elusive. Here, we demonstrate that adenosine within aging tissues actively reprograms CD8+ T cells into a pro-aging Granzyme K+ (Gzmk+) population. Mechanistically, senescent cells create an adenosine-rich niche via p16-dependent CD39 upregulation, triggering A2aR signaling to induce Gzmk+ T cell differentiation. Once released, Gzmk promotes systemic inflammaging through PAR1 and complement activation. Crucially, targeting this axis--either via genetic Gzmk ablation or pharmacological A2aR blockade--reverses multi-organ aging phenotypes and significantly extends healthy lifespan in mice. Human analysis reveals age-dependent Gzmk+ T cell accumulation in multi organs, while coffee intake (an A2aR antagonist) inversely correlates with plasma Gzmk levels. Our findings uncover how metabolic niche changes drive T cell aging and establish the adenosine-Gzmk axis as a pivotal therapeutic target for combating age-related diseases.

immunology↗

A Spatiotemporal Molecular Switch Governs Plant Asymmetric Cell Division

Asymmetric cell division (ACD) often requires protein polarization in the mother cell to produce daughter cells with distinct identities ("cell-fate asymmetry"). Here, we define a previously undocumented mechanism for establishing cell-fate asymmetry in Arabidopsis stomatal stem cells. In particular, we show that polarization of BSL protein phosphatases promotes stomatal ACD by establishing a "kinase-based signaling asymmetry" in the two daughter cells. BSL polarization in the stomatal ACD mother cell is triggered upon commitment to cell division. Polarized BSL is inherited by the differentiating daughter cell where it suppresses cell division and promotes cell-fate determination. Plants lacking BSL exhibit stomatal over-proliferation, demonstrating BSL plays an essential role in stomatal development. Our findings establish that BSL polarization provides a spatiotemporal molecular switch that enables cell-fate asymmetry in stomatal ACD daughter cells. We propose BSL polarization is triggered by an ACD "checkpoint" in the mother cell that monitors establishment of division-plane asymmetry.

plant biology↗

Sex differences in electrophysiological properties of mouse mPOA neurons revealed by in vitro whole-cell recordings

The medial preoptic area (mPOA) of the hypothalamus is sexually dimorphic and controls sexually dimorphic display of male mating and parental care. Yet, despite extensive characterization of sex differences in the mPOA, we know surprisingly little about whether or how male and female mPOA neurons differ electrophysiologically, which relate more directly to neuronal firing and behavioral pattern generation. In this study, we performed whole-cell patch clamp recordings of the mPOA in acute brain slices cut from virgin adult mice, and compared in total 29 electrophysiological parameters between male and female mPOA neurons. We find that resting membrane potential (Vm), input resistance (Rm), time constant ({tau}m), threshold (Vth) and minimum current (rheobase) required to generate an action potential differ significantly between male and female in a cell-type dependent manner. Nonetheless, there is little evidence for profuse sex differences in neuronal excitability, except for a higher probability of rebound neurons in males. Depletion of male gonadal hormones in adulthood partially de-masculinizes sexually dimorphic electrophysiological parameters, suggesting that some of these sex differences may establish during development. Furthermore, as a demonstration of the behavioral relevance of these sex differences, we show that pharmacologic blockage of currents mediated by T-type Ca2+ channel, which underlie rebound and tends to be larger in male mPOA neurons, result in behavioral deficits in male mating. In summary, we have identified key sex differences in electrophysiological properties of mPOA neurons that likely contribute to sexually dimorphic display of behaviors.\n\nSignificance StatementSex represents an important biological variable that impact an individuals behaviors, physiology and disease susceptibility. Indeed, sex differences in the nervous system manifest across many different levels and scales. Yet, throughout previous multifaceted investigations on sex differences in the brain, electrophysiological characterizations, which could potentially bridge cellular and molecular sex differences with sexually dimorphic brain functions and behaviors, remains scant. Here, focusing on an evolutionarily conserved sexually dimorphic nucleus, we investigated sex differences in electrophysiological properties of mPOA neurons and its modulation by gonadal hormones in adult males via in vitro whole-cell patch clamp. As a result, we identified novel sex differences in electrophysiological properties that likely contribute to sexually dimorphic display of behaviors and physiological functions.

neuroscience↗