Person: Gertner, Rona
Loading...
Email Address
AA Acceptance Date
Birth Date
Research Projects
Organizational Units
Job Title
Last Name
Gertner
First Name
Rona
Name
Gertner, Rona
5 results
Search Results
Now showing 1 - 5 of 5
Publication Nuclear magnetic resonance detection and spectroscopy of single proteins using quantum logic(American Association for the Advancement of Science (AAAS), 2016) Lovchinsky, Igor; Sushkov, Alexander; Urbach, Elana; de Leon, Nathalie Pulmones; Choi, Soonwon; De Greve, Kristiaan; Evans, Ruffin; Gertner, Rona; Bersin, Eric; Muller, Christopher Michael; McGuinness, L.; Jelezko, F.; Walsworth, Ronald; Park, Hongkun; Lukin, MikhailNuclear magnetic resonance spectroscopy is a powerful tool for the structural analysis of organic compounds and biomolecules but typically requires macroscopic sample quantities. We use a sensor, which consists of two quantum bits corresponding to an electronic spin and an ancillary nuclear spin, to demonstrate room temperature magnetic resonance detection and spectroscopy of multiple nuclear species within individual ubiquitin proteins attached to the diamond surface. Using quantum logic to improve readout fidelity and a surface-treatment technique to extend the spin coherence time of shallow nitrogen-vacancy centers, we demonstrate magnetic field sensitivity sufficient to detect individual proton spins within 1 second of integration. This gain in sensitivity enables high-confidence detection of individual proteins and allows us to observe spectral features that reveal information about their chemical composition.Publication Single-cell transcriptomics reveals bimodality in expression and splicing in immune cells(2013) Shalek, Alex K.; Satija, Rahul; Adiconis, Xian; Gertner, Rona; Gaublomme, Jellert; Raychowdhury, Raktima; Schwartz, Schragi; Yosef, Nir; Malboeuf, Christine; Lu, Diana; Trombetta, John T.; Gennert, Dave; Gnirke, Andreas; Goren, Alon; Hacohen, Nir; Levin, Joshua Z.; Park, Hongkun; Regev, AvivRecent molecular studies have revealed that, even when derived from a seemingly homogenous population, individual cells can exhibit substantial differences in gene expression, protein levels, and phenotypic output1–5, with important functional consequences4,5. Existing studies of cellular heterogeneity, however, have typically measured only a few pre-selected RNAs1,2 or proteins5,6 simultaneously because genomic profiling methods3 could not be applied to single cells until very recently7–10. Here, we use single-cell RNA-Seq to investigate heterogeneity in the response of bone marrow derived dendritic cells (BMDCs) to lipopolysaccharide (LPS). We find extensive, and previously unobserved, bimodal variation in mRNA abundance and splicing patterns, which we validate by RNA-fluorescence in situ hybridization (RNA-FISH) for select transcripts. In particular, hundreds of key immune genes are bimodally expressed across cells, surprisingly even for genes that are very highly expressed at the population average. Moreover, splicing patterns demonstrate previously unobserved levels of heterogeneity between cells. Some of the observed bimodality can be attributed to closely related, yet distinct, known maturity states of BMDCs; other portions reflect differences in the usage of key regulatory circuits. For example, we identify a module of 137 highly variable, yet co-regulated, antiviral response genes. Using cells from knockout mice, we show that variability in this module may be propagated through an interferon feedback circuit involving the transcriptional regulators Stat2 and Irf7. Our study demonstrates the power and promise of single-cell genomics in uncovering functional diversity between cells and in deciphering cell states and circuits.Publication 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, AvivHigh-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.Publication Nanowire-Mediated Delivery Enables Functional Interrogation of Primary Immune Cells: Application to the Analysis of Chronic Lymphocytic Leukemia(American ChemicalSociety, 2012) Shalek, Alexander; Gaublomme, Jellert; Wang, Lili; Yosef, Nir; Chevrier, Nicolas; Andersen, Mette S.; Robinson, Jacob T.; Pochet, Nathalie; Neuberg, Donna; Gertner, Rona; Amit, Ido; Brown, Jennifer; Hacohen, Nir; Regev, Aviv; Wu, Catherine; Park, HongkunA circuit level understanding of immune cells and hematological cancers has been severely impeded by a lack of techniques that enable intracellular perturbation without significantly altering cell viability and function. Here, we demonstrate that vertical silicon nanowires (NWs) enable gene-specific manipulation of diverse murine and human immune cells with negligible toxicity. To illustrate the power of the technique, we then apply NW-mediated gene silencing to investigate the role of the Wnt signaling pathway in chronic lymphocytic leukemia (CLL). Remarkably, CLL-B cells from different patients exhibit tremendous heterogeneity in their response to the knockdown of a single gene, LEF1. This functional heterogeneity defines three distinct patient groups not discernible by conventional CLL cytogenetic markers and provides a prognostic indicator for patients’ time to first therapy. Analyses of gene expression signatures associated with these functional patient subgroups reveal unique insights into the underlying molecular basis for disease heterogeneity. Overall, our findings suggest a functional classification that can potentially guide the selection of patient-specific therapies in CLL and highlight the opportunities for nanotechnology to drive biological inquiry.Publication Synaptic connectivity mapping among thousands of neurons via parallelized intracellular recording with a microhole electrode array(Springer Science and Business Media LLC, 2025-02-11) Wang, Jun; Jung, Woo-Bin; Gertner, Rona; Park, Hongkun; Ham, DonheeMassive parallelization of neuronal intracellular recording, which can measure synaptic signals across a network and thus can enable the mapping and characterization of synaptic connections, is a challenge still open in neuroscience, with the state-of-the-art limited to a mapping of ~300 synaptic connections. Here, we report a 4,096 platinum/platinum-black microhole electrode array fabricated on a complementary metal-oxide semiconductor electronic chip that substantially advances parallel intracellular recording and synaptic connectivity mapping. The microhole-neuron interface, together with current-clamp electronics in the underlying semiconductor chip, allows 90% average intracellular coupling rate with rat neuronal cultures, generating network-wide intracellular recording data that abound with synaptic signals. From these data we extract 70,000+ plausible synaptic connections amongst 2,000+ neurons, and catalogue them into inhibitory, weak/uneventful excitatory, and strong/eventful excitatory chemical synaptic connections, and electrical synaptic connections, with an estimated overall error rate of around 5%. The reported scale of synaptic connection mapping, with the ability to characterize synaptic connections, provides a step toward functional connectivity mapping of a large-scale neuronal network.