All Publications


  • Coordination of two enhancers drives expression of olfactory trace amine-associated receptors NATURE COMMUNICATIONS Fei, A., Wu, W., Tan, L., Tang, C., Xu, Z., Huo, X., Bao, H., Kong, Y., Johnson, M., Hartmann, G., Talay, M., Yang, C., Riegler, C., Herrera, K. J., Engert, F., Xie, X., Barnea, G., Liberles, S. D., Yang, H., Li, Q. 2021; 12 (1): 3798

    Abstract

    Olfactory sensory neurons (OSNs) are functionally defined by their expression of a unique odorant receptor (OR). Mechanisms underlying singular OR expression are well studied, and involve a massive cross-chromosomal enhancer interaction network. Trace amine-associated receptors (TAARs) form a distinct family of olfactory receptors, and here we find that mechanisms regulating Taar gene choice display many unique features. The epigenetic signature of Taar genes in TAAR OSNs is different from that in OR OSNs. We further identify that two TAAR enhancers conserved across placental mammals are absolutely required for expression of the entire Taar gene repertoire. Deletion of either enhancer dramatically decreases the expression probabilities of different Taar genes, while deletion of both enhancers completely eliminates the TAAR OSN populations. In addition, both of the enhancers are sufficient to drive transgene expression in the partially overlapped TAAR OSNs. We also show that the TAAR enhancers operate in cis to regulate Taar gene expression. Our findings reveal a coordinated control of Taar gene choice in OSNs by two remote enhancers, and provide an excellent model to study molecular mechanisms underlying formation of an olfactory subsystem.

    View details for DOI 10.1038/s41467-021-23823-4

    View details for Web of Science ID 000665041200004

    View details for PubMedID 34145235

    View details for PubMedCentralID PMC8213717

  • MALIGNANT SYNAPTIC PLASTICITY IN PEDIATRIC HIGH-GRADE GLIOMAS Taylor, K., Barron, T., Hartmann, G., Zhang, H., Hui, A., Gillespie, S., Monje, M. OXFORD UNIV PRESS INC. 2021: 21
  • Emergence of a High-Plasticity Cell State during Lung Cancer Evolution CANCER CELL Marjanovic, N., Hofree, M., Chan, J. E., Canner, D., Wu, K., Trakala, M., Hartmann, G. G., Smith, O. C., Kim, J. Y., Evans, K., Hudson, A., Ashenberg, O., Porter, C. M., Bejnood, A., Subramanian, A., Pitter, K., Yan, Y., Delorey, T., Phillips, D. R., Shah, N., Chaudhary, O., Tsankov, A., Hollmann, T., Rekhtman, N., Massion, P. P., Poirier, J. T., Mazutis, L., Li, R., Lee, J., Amon, A., Rudin, C. M., Jacks, T., Regev, A., Tammela, T. 2020; 38 (2): 229-+

    Abstract

    Tumor evolution from a single cell into a malignant, heterogeneous tissue remains poorly understood. Here, we profile single-cell transcriptomes of genetically engineered mouse lung tumors at seven stages, from pre-neoplastic hyperplasia to adenocarcinoma. The diversity of transcriptional states increases over time and is reproducible across tumors and mice. Cancer cells progressively adopt alternate lineage identities, computationally predicted to be mediated through a common transitional, high-plasticity cell state (HPCS). Accordingly, HPCS cells prospectively isolated from mouse tumors and human patient-derived xenografts display high capacity for differentiation and proliferation. The HPCS program is associated with poor survival across human cancers and demonstrates chemoresistance in mice. Our study reveals a central principle underpinning intra-tumoral heterogeneity and motivates therapeutic targeting of the HPCS.

    View details for DOI 10.1016/j.ccell.2020.06.012

    View details for Web of Science ID 000559591600011

    View details for PubMedID 32707077

    View details for PubMedCentralID PMC7745838

  • Transsynaptic Mapping of Second-Order Taste Neurons in Flies by trans-Tango NEURON Talay, M., Richman, E. B., Snell, N. J., Hartmann, G. G., Fisher, J. D., Sorkac, A., Santoyo, J. F., Chou-Freed, C., Nair, N., Johnson, M., Szymanski, J. R., Barnea, G. 2017; 96 (4): 783-+

    Abstract

    Mapping neural circuits across defined synapses is essential for understanding brain function. Here we describe trans-Tango, a technique for anterograde transsynaptic circuit tracing and manipulation. At the core of trans-Tango is a synthetic signaling pathway that is introduced into all neurons in the animal. This pathway converts receptor activation at the cell surface into reporter expression through site-specific proteolysis. Specific labeling is achieved by presenting a tethered ligand at the synapses of genetically defined neurons, thereby activating the pathway in their postsynaptic partners and providing genetic access to these neurons. We first validated trans-Tango in the Drosophila olfactory system and then implemented it in the gustatory system, where projections beyond the first-order receptor neurons are not fully characterized. We identified putative second-order neurons within the sweet circuit that include projection neurons targeting known neuromodulation centers in the brain. These experiments establish trans-Tango as a flexible platform for transsynaptic circuit analysis.

    View details for DOI 10.1016/j.neuron.2017.10.011

    View details for Web of Science ID 000415310800011

    View details for PubMedID 29107518

    View details for PubMedCentralID PMC5693608