Biology subjects

Zhao, X.-F.

Publications and source records attributed to Zhao, X.-F..

3 recordsLinked to original sources

bioRxiv2022

The Injured Sciatic Nerve Atlas (iSNAT), Insights into the Cellular and Molecular Basis of Neural Tissue Degeneration and Regeneration

Upon trauma, the adult murine PNS displays a remarkable degree of spontaneous anatomical and functional regeneration. To explore extrinsic mechanisms of neural repair, we carried out single cell analysis of naive mouse sciatic nerve, peripheral blood mononuclear cells, and crushed sciatic nerves at 1-day, 3-days, and 7-days following injury. During the first week, monocytes and macrophages (Mo/Mac) rapidly accumulate in the injured nerve and undergo extensive metabolic reprogramming. Proinflammatory Mo/Mac in the injured nerve show high glycolytic flux compared to Mo/Mac in blood and dominate the early injury response. They subsequently give way to inflammation resolving Mac, programmed toward oxidative phosphorylation. Nerve crush injury causes partial leakiness of the blood-nerve-barrier, proliferation of endoneurial and perineurial stromal cells, and accumulation of select serum proteins. Micro-dissection of the nerve injury site and distal nerve, followed by single-cell RNA-sequencing, identified distinct immune compartments, triggered by mechanical nerve wounding and Wallerian degeneration, respectively. This finding was independently confirmed with Sarm1-/- mice, where Wallerian degeneration is greatly delayed. Experiments with chimeric mice showed that wildtype immune cells readily enter the injury site in Sarm1-/- mice, but are sparse in the distal nerve, except for Mo. We used CellChat to explore intercellular communications in the naive and injured PNS and report on hundreds of ligand-receptor interactions. Our longitudinal analysis represents a new resource for nerve regeneration, reveals location specific immune microenvironments, and reports on large intercellular communication networks. To facilitate mining of scRNAseq datasets, we generated the injured sciatic nerve atlas (iSNAT): https://cdb-rshiny.med.umich.edu/Giger_iSNAT/

neuroscience↗

bioRxiv2021

Plexins Promote Hedgehog Signaling Through Their Cytoplasmic GAP Activity

Hedgehog signaling controls tissue patterning during embryonic and postnatal development and continues to play important roles throughout life. Characterizing the full complement of Hedgehog pathway components is essential to understanding its wide- ranging functions. Previous work has identified Neuropilins, established Semaphorin receptors, as positive regulators of Hedgehog signaling. Neuropilins require Plexin co- receptors to mediate Semaphorin signaling, but a role for Plexins in Hedgehog signaling has not yet been explored. Here, we provide evidence that multiple Plexins promote Hedgehog signaling in NIH/3T3 fibroblasts and that Plexin loss-of-function in these cells results in significantly reduced Hedgehog pathway activity. Catalytic activity of the Plexin GTPase activating protein (GAP) domain is required for Hedgehog signal promotion, and constitutive activation of the GAP domain further amplifies Hedgehog signaling. Additionally, we demonstrate that Plexins promote Hedgehog signaling at the level of GLI transcription factors and that this promotion requires intact primary cilia. Finally, we find that Plexin loss-of-function significantly reduces the response to Hedgehog pathway activation in the mouse dentate gyrus. Together, these data identify Plexins as novel components of the Hedgehog pathway and provide insight into their mechanism of action.

developmental biology↗

bioRxiv2020

Seasonal climate variations promote bacterial α-diversity in soil

Ecological theory suggests that temporal environmental fluctuations can contribute greatly to diversity maintenance. Given bacterias short generation time and rapid responses to environmental change, seasonal climate fluctuations are very likely to play an important role in maintaining the extremely high -diversity of soil bacterial community, which has been unfortunately neglected in previous studies. Here, with in-depth analyses of two previously published soil bacterial datasets at global scale, we found that soil bacterial -diversity was positively correlated with both seasonal variations of temperature and precipitation. Furthermore, piecewise structural equation models showed that seasonal variations of temperature or precipitation directly promoted soil bacterial -diversity in each dataset. However, it is noteworthy that the importance of seasonal climate variations might be underestimated in the above analyses, due to the high level of environmental variations irrelevant to climate seasonality among sampling sites and the lack of sampling across seasons. Supplementary analyses of a previously published wheat cropland dataset with samples collected in both summer and winter across North China Plain was conducted. Similarly, we found that bacterial -diversity was positively correlated with seasonal climate variations, but much stronger, though the range of seasonal climate variations was much smaller compared to the two global datasets. Collectively, these findings implied that fluctuation-dependent mechanisms of diversity maintenance presumably operate in soil bacterial communities. Based on existing evidence, we speculated that the storage effect may be the main mechanism responsible for diversity maintenance in soil bacterial community, but rigorous experimental tests are needed in the future.

ecology↗