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Ding, Ruihua

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Ding

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Ruihua

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Ding, Ruihua

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2014 - 20192

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Author's Publications: search.filters.isAuthorOfPublication.9611255f-c5ac-468b-8687-edf061b4078b

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    Remotely Controlled Chemomagnetic Modulation of Targeted Neural Circuits
    (Springer Science and Business Media LLC, 2019-08-19) Rao, Siyuan; Chen, Ritchie; LaRocca, Ava; Christiansen, Michael; Senko, Alexander; Shi, Cindy; Chiang, Po-Han; Varnavides, Georgios; Xue, Jian; Zhou, Yang; Park, Seongjun; Ding, Ruihua; Moon, Junsang; Feng, Guoping; Anikeeva, Polina
    Connecting neural circuit output to behaviour can be facilitated by precise chemical manipulation of specific cell populations1,2. Engineered receptors exclusively activated by designer small molecules enable manipulation of specific neural pathways3,4. Their application to studies of behaviour has thus far been hampered by a trade-off between low temporal resolution of systemic injection versus invasiveness of implanted cannulas or infusion pumps2. Here, we develop remotely controlled chemomagnetic modulation – a nanomaterials-based technique that permits pharmacological interrogation of targeted neural populations in freely moving subjects. The heat dissipated by magnetic nanoparticles in the presence of alternating magnetic fields triggers small molecule release from thermally sensitive lipid vesicles with 20 s latency. Coupled with chemogenetic activation of engineered receptors, this technique permits the control of specific neurons with temporal and spatial precision. Delivery of chemomagnetic particles to the ventral tegmental area allows remote modulation of motivated behaviour in mice. Furthermore, this chemomagnetic approach activates endogenous circuits by enabling regulated release of receptor ligands. Applied to an endogenous dopamine receptor D1 agonist in the nucleus accumbens, a brain area involved in mediating social interactions, chemomagnetic modulation increases sociability in mice. By offering temporally precise control of specified ligand-receptor interactions in neurons, this approach may facilitate molecular neuroscience studies in behaving organisms.
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    Single cell RNA Seq reveals dynamic paracrine control of cellular variation
    (2014) Shalek, Alex K.; Satija, Rahul; Shuga, Joe; Trombetta, John J.; Gennert, Dave; Lu, Diana; Chen, Peilin; Gertner, Rona; Gaublomme, Jellert; Yosef, Nir; Schwartz, Schraga; Fowler, Brian; Weaver, Suzanne; Wang, Jing; Wang, Xiaohui; Ding, Ruihua; Raychowdhury, Raktima; Friedman, Nir; Hacohen, Nir; Park, Hongkun; May, Andrew P.; Regev, Aviv
    High-throughput single-cell transcriptomics offers an unbiased approach for understanding the extent, basis, and function of gene expression variation between seemingly identical cells. Here, we sequence single-cell RNA-Seq libraries prepared from over 1,700 primary mouse bone marrow derived dendritic cells (DCs) spanning several experimental conditions. We find substantial variation between identically stimulated DCs, in both the fraction of cells detectably expressing a given mRNA and the transcript’s level within expressing cells. Distinct gene modules are characterized by different temporal heterogeneity profiles. In particular, a “core” module of antiviral genes is expressed very early by a few “precocious” cells, but is later activated in all cells. By stimulating cells individually in sealed microfluidic chambers, analyzing DCs from knockout mice, and modulating secretion and extracellular signaling, we show that this response is coordinated via interferon-mediated paracrine signaling. Surprisingly, preventing cell-to-cell communication also substantially reduces variability in the expression of an early-induced “peaked” inflammatory module, suggesting that paracrine signaling additionally represses part of the inflammatory program. Our study highlights the importance of cell-to-cell communication in controlling cellular heterogeneity and reveals general strategies that multicellular populations use to establish complex dynamic responses.