Colleen McLaughlin

All Publications

• Scent of a human: The mosquito olfactory system defies dogma to ensure attraction to humans. Cell McLaughlin, C. N., Luo, L. 2022; 185 (17): 3079-3081

  Abstract

  Mosquitoes are strongly attracted to humans, and their bites not only cause intense itch but can beget severe diseases. In this issue of Cell, Herre etal. reveal that non-canonical olfactory circuit organization and coding likely endow mosquitoes with a robust ability to locate human hosts.

  View details for DOI 10.1016/j.cell.2022.07.018

  View details for PubMedID 35985284

• Isolation and RNA sequencing of single nuclei from Drosophila tissues. STAR protocols McLaughlin, C. N., Qi, Y., Quake, S. R., Luo, L., Li, H. 2022; 3 (2): 101417

  Abstract

  Many insect cells are encapsulated within the exoskeleton and cannot be dissociated intact, making them inaccessible to single-cell transcriptomic profiling. We have used single-nucleus RNA sequencing to extract transcriptomic information from multiple Drosophila tissues. Here, we describe procedures for the (1) dissociation of single nuclei, (2) isolation of single nuclei using two popular cell sorters, and (3) preparation of libraries for Smart-seq2 and 10× Genomics. This protocol enables generation of high-quality transcriptomes from single nuclei and can be applied to other species. For complete details on the use and execution of this protocol, please refer to McLaughlin et al. (2021) and Li et al. (2022).

  View details for DOI 10.1016/j.xpro.2022.101417

  View details for PubMedID 35620068

  View details for PubMedCentralID PMC9127693

• Fly Cell Atlas: A single-nucleus transcriptomic atlas of the adult fruit fly. Science (New York, N.Y.) Li, H., Janssens, J., De Waegeneer, M., Kolluru, S. S., Davie, K., Gardeux, V., Saelens, W., David, F. P., Brbic, M., Spanier, K., Leskovec, J., McLaughlin, C. N., Xie, Q., Jones, R. C., Brueckner, K., Shim, J., Tattikota, S. G., Schnorrer, F., Rust, K., Nystul, T. G., Carvalho-Santos, Z., Ribeiro, C., Pal, S., Mahadevaraju, S., Przytycka, T. M., Allen, A. M., Goodwin, S. F., Berry, C. W., Fuller, M. T., White-Cooper, H., Matunis, E. L., DiNardo, S., Galenza, A., O'Brien, L. E., Dow, J. A., FCA Consortium, Jasper, H., Oliver, B., Perrimon, N., Deplancke, B., Quake, S. R., Luo, L., Aerts, S., Agarwal, D., Ahmed-Braimah, Y., Arbeitman, M., Ariss, M. M., Augsburger, J., Ayush, K., Baker, C. C., Banisch, T., Birker, K., Bodmer, R., Bolival, B., Brantley, S. E., Brill, J. A., Brown, N. C., Buehner, N. A., Cai, X. T., Cardoso-Figueiredo, R., Casares, F., Chang, A., Clandinin, T. R., Crasta, S., Desplan, C., Detweiler, A. M., Dhakan, D. B., Dona, E., Engert, S., Floc'hlay, S., George, N., Gonzalez-Segarra, A. J., Groves, A. K., Gumbin, S., Guo, Y., Harris, D. E., Heifetz, Y., Holtz, S. L., Horns, F., Hudry, B., Hung, R., Jan, Y. N., Jaszczak, J. S., Jefferis, G. S., Karkanias, J., Karr, T. L., Katheder, N. S., Kezos, J., Kim, A. A., Kim, S. K., Kockel, L., Konstantinides, N., Kornberg, T. B., Krause, H. M., Labott, A. T., Laturney, M., Lehmann, R., Leinwand, S., Li, J., Li, J. S., Li, K., Li, K., Li, L., Li, T., Litovchenko, M., Liu, H., Liu, Y., Lu, T., Manning, J., Mase, A., Matera-Vatnick, M., Matias, N. R., McDonough-Goldstein, C. E., McGeever, A., McLachlan, A. D., Moreno-Roman, P., Neff, N., Neville, M., Ngo, S., Nielsen, T., O'Brien, C. E., Osumi-Sutherland, D., Ozel, M. N., Papatheodorou, I., Petkovic, M., Pilgrim, C., Pisco, A. O., Reisenman, C., Sanders, E. N., Dos Santos, G., Scott, K., Sherlekar, A., Shiu, P., Sims, D., Sit, R. V., Slaidina, M., Smith, H. E., Sterne, G., Su, Y., Sutton, D., Tamayo, M., Tan, M., Tastekin, I., Treiber, C., Vacek, D., Vogler, G., Waddell, S., Wang, W., Wilson, R. I., Wolfner, M. F., Wong, Y. E., Xie, A., Xu, J., Yamamoto, S., Yan, J., Yao, Z., Yoda, K., Zhu, R., Zinzen, R. P. 2022; 375 (6584): eabk2432

  Abstract

  For more than 100 years, the fruit fly Drosophila melanogaster has been one of the most studied model organisms. Here, we present a single-cell atlas of the adult fly, Tabula Drosophilae, that includes 580,000 nuclei from 15 individually dissected sexed tissues as well as the entire head and body, annotated to >250 distinct cell types. We provide an in-depth analysis of cell type-related gene signatures and transcription factor markers, as well as sexual dimorphism, across the whole animal. Analysis of common cell types between tissues, such as blood and muscle cells, reveals rare cell types and tissue-specific subtypes. This atlas provides a valuable resource for the Drosophila community and serves as a reference to study genetic perturbations and disease models at single-cell resolution.

  View details for DOI 10.1126/science.abk2432

  View details for PubMedID 35239393

• Temporal evolution of single-cell transcriptomes of Drosophila olfactory projection neurons. eLife Xie, Q., Brbic, M., Horns, F., Kolluru, S. S., Jones, R. C., Li, J., Reddy, A. R., Xie, A., Kohani, S., Li, Z., McLaughlin, C. N., Li, T., Xu, C., Vacek, D., Luginbuhl, D. J., Leskovec, J., Quake, S. R., Luo, L., Li, H. 2021; 10

  Abstract

  Neurons undergo substantial morphological and functional changes during development to form precise synaptic connections and acquire specific physiological properties. What are the underlying transcriptomic bases? Here, we obtained the single-cell transcriptomes of Drosophila olfactory projection neurons (PNs) at four developmental stages. We decoded the identity of 21 transcriptomic clusters corresponding to 20 PN types and developed methods to match transcriptomic clusters representing the same PN type across development. We discovered that PN transcriptomes reflect unique biological processes unfolding at each stage-neurite growth and pruning during metamorphosis at an early pupal stage; peaked transcriptomic diversity during olfactory circuit assembly at mid-pupal stages; and neuronal signaling in adults. At early developmental stages, PN types with adjacent birth order share similar transcriptomes. Together, our work reveals principles of cellular diversity during brain development and provides a resource for future studies of neural development in PNs and other neuronal types.

  View details for DOI 10.7554/eLife.63450

  View details for PubMedID 33427646

• Single-cell transcriptomes of developing and adult olfactory receptor neurons in Drosophila. eLife McLaughlin, C. N., Brbić, M. n., Xie, Q. n., Li, T. n., Horns, F. n., Kolluru, S. S., Kebschull, J. M., Vacek, D. n., Xie, A. n., Li, J. n., Jones, R. C., Leskovec, J. n., Quake, S. R., Luo, L. n., Li, H. n. 2021; 10

  Abstract

  Recognition of environmental cues is essential for the survival of all organisms. Transcriptional changes occur to enable the generation and function of the neural circuits underlying sensory perception. To gain insight into these changes, we generated single-cell transcriptomes of Drosophila olfactory- (ORNs), thermo-, and hygro-sensory neurons at an early developmental and adult stage using single-cell and single-nucleus RNA sequencing. We discovered that ORNs maintain expression of the same olfactory receptors across development. Using receptor expression and computational approaches, we matched transcriptomic clusters corresponding to anatomically and physiologically defined neuron types across multiple developmental stages. We found that cell-type-specific transcriptomes partly reflected axon trajectory choices in development and sensory modality in adults. We uncovered stage-specific genes that could regulate the wiring and sensory responses of distinct ORN types. Collectively, our data reveal transcriptomic features of sensory neuron biology and provide a resource for future studies of their development and physiology.

  View details for DOI 10.7554/eLife.63856

  View details for PubMedID 33555999

• Cell-Surface Proteomic Profiling in the Fly Brain Uncovers Wiring Regulators. Cell Li, J., Han, S., Li, H., Udeshi, N. D., Svinkina, T., Mani, D. R., Xu, C., Guajardo, R., Xie, Q., Li, T., Luginbuhl, D. J., Wu, B., McLaughlin, C. N., Xie, A., Kaewsapsak, P., Quake, S. R., Carr, S. A., Ting, A. Y., Luo, L. 2020

  Abstract

  Molecular interactions at the cellular interface mediate organized assembly of single cells into tissues and, thus, govern the development and physiology of multicellular organisms. Here, we developed a cell-type-specific, spatiotemporally resolved approach to profile cell-surface proteomes in intact tissues. Quantitative profiling of cell-surface proteomes of Drosophila olfactory projection neurons (PNs) in pupae and adults revealed global downregulation of wiring molecules and upregulation of synaptic molecules in the transition from developing to mature PNs. A proteome-instructed invivo screen identified 20 cell-surface molecules regulating neural circuit assembly, many of which belong to evolutionarily conserved protein families not previously linked to neural development. Genetic analysis further revealed that the lipoprotein receptor LRP1 cell-autonomously controls PN dendrite targeting, contributing to the formation of a precise olfactory map. These findings highlight the power of temporally resolved in situ cell-surface proteomic profiling in discovering regulators of brain wiring.

  View details for DOI 10.1016/j.cell.2019.12.029

  View details for PubMedID 31955847

• Single-Cell Transcriptomes Reveal Diverse Regulatory Strategies for Olfactory Receptor Expression and Axon Targeting. Current biology : CB Li, H. n., Li, T. n., Horns, F. n., Li, J. n., Xie, Q. n., Xu, C. n., Wu, B. n., Kebschull, J. M., McLaughlin, C. N., Kolluru, S. S., Jones, R. C., Vacek, D. n., Xie, A. n., Luginbuhl, D. J., Quake, S. R., Luo, L. n. 2020

  Abstract

  The regulatory mechanisms by which neurons coordinate their physiology and connectivity are not well understood. The Drosophila olfactory receptor neurons (ORNs) provide an excellent system to investigate this question. Each ORN type expresses a unique olfactory receptor, or a combination thereof, and sends their axons to a stereotyped glomerulus. Using single-cell RNA sequencing, we identified 33 transcriptomic clusters for ORNs and mapped 20 to their glomerular types, demonstrating that transcriptomic clusters correspond well with anatomically and physiologically defined ORN types. Each ORN type expresses hundreds of transcription factors. Transcriptome-instructed genetic analyses revealed that (1) one broadly expressed transcription factor (Acj6) only regulates olfactory receptor expression in one ORN type and only wiring specificity in another type, (2) one type-restricted transcription factor (Forkhead) only regulates receptor expression, and (3) another type-restricted transcription factor (Unplugged) regulates both events. Thus, ORNs utilize diverse strategies and complex regulatory networks to coordinate their physiology and connectivity.

  View details for DOI 10.1016/j.cub.2020.01.049

  View details for PubMedID 32059767