1. Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq.

    Science 352(6282):189 (2016) PMID 27124452 PMCID PMC4944528

    To explore the distinct genotypic and phenotypic states of melanoma tumors, we applied single-cell RNA sequencing (RNA-seq) to 4645 single cells isolated from 19 patients, profiling malignant, immune, stromal, and endothelial cells. Malignant cells within the same tumor displayed transcriptional...
  2. Multiplexed barcoded CRISPR-Cas9 screening enabled by CombiGEM.

    PNAS 113(9):2544 (2016) PMID 26864203 PMCID PMC4780610

    The orchestrated action of genes controls complex biological phenotypes, yet the systematic discovery of gene and drug combinations that modulate these phenotypes in human cells is labor intensive and challenging to scale. Here, we created a platform for the massively parallel screening of barco...
  3. Innate Lymphoid Cells Are Depleted Irreversibly during Acute HIV-1 Infection in the Absence of Viral Suppression.

    Immunity 44(2):391 (2016) PMID 26850658

    Innate lymphoid cells (ILCs) play a central role in the response to infection by secreting cytokines crucial for immune regulation, tissue homeostasis, and repair. Although dysregulation of these systems is central to pathology, the impact of HIV-1 on ILCs remains unknown. We found that human bl...
  4. A microfluidic platform enabling single-cell RNA-seq of multigenerational lineages.

    Nature Communications 7:10220 (2016) PMID 26732280 PMCID PMC4729820

    We introduce a microfluidic platform that enables off-chip single-cell RNA-seq after multi-generational lineage tracking under controlled culture conditions. We use this platform to generate whole-transcriptome profiles of primary, activated murine CD8+ T-cell and lymphocytic leukemia cell line ...
  5. Single-Cell Genomics Unveils Critical Regulators of Th17 Cell Pathogenicity.

    Cell 163(6):1400 (2015) PMID 26607794 PMCID PMC4671824

    Extensive cellular heterogeneity exists within specific immune-cell subtypes classified as a single lineage, but its molecular underpinnings are rarely characterized at a genomic scale. Here, we use single-cell RNA-seq to investigate the molecular mechanisms governing heterogeneity and pathogeni...
  6. Pathogen Cell-to-Cell Variability Drives Heterogeneity in Host Immune Responses.

    Cell 162(6):1309 (2015) PMID 26343579 PMCID PMC4578813

    Encounters between immune cells and invading bacteria ultimately determine the course of infection. These interactions are usually measured in populations of cells, masking cell-to-cell variation that may be important for infection outcome. To characterize the gene expression variation that unde...
  7. MERFISHing for spatial context.

    Trends in Immunology 36(7):390 (2015) PMID 26013647

    A new paper in Science by Zhuang and colleagues introduces multiplexed error-robust FISH (MERFISH). MERFISH extends single-molecule imaging techniques to profile the copy number and localization patterns of thousands of genes, representing a major advance for spatial transcriptomics, with exciti...
  8. Highly Parallel Genome-wide Expression Profiling of Individual Cells Using Nanoliter Droplets.

    Cell 161(5):1202 (2015) PMID 26000488 PMCID PMC4481139

    Cells, the basic units of biological structure and function, vary broadly in type and state. Single-cell genomics can characterize cell identity and function, but limitations of ease and scale have prevented its broad application. Here we describe Drop-seq, a strategy for quickly profiling thous...
  9. MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data.

    Genome Biology 16(1):278 (2015) PMID 26653891

    Single-cell transcriptomics reveals gene expression heterogeneity but suffers from stochastic dropout and characteristic bimodal expression distributions in which expression is either strongly non-zero or non-detectable. We propose a two-part, generalized linear model for such bimodal data that ...
  10. Marrying microfluidics and microwells for parallel, high-throughput single-cell genomics.

    Genome Biology 16(1):129 (2015) PMID 26087845 PMCID PMC4474330

    An innovative, microwell-based platform for single-cell RNA sequencing (RNA-seq) combines cost efficiency, scalability and parallelizability, and will enable many new avenues of biological inquiry.See related Research article: http://dx.doi.org/10.1186/s13059-015-0684-3.
  11. Deconstructing transcriptional heterogeneity in pluripotent stem cells.

    Nature 516(7529):56 (2014) PMID 25471879 PMCID PMC4256722

    Pluripotent stem cells (PSCs) are capable of dynamic interconversion between distinct substates; however, the regulatory circuits specifying these states and enabling transitions between them are not well understood. Here we set out to characterize transcriptional heterogeneity in mouse PSCs by ...
  12. Somatic mutation as a mechanism of Wnt/β-catenin pathway activation in CLL.

    Blood 124(7):1089 (2014) PMID 24778153 PMCID PMC4133483

    One major goal of cancer genome sequencing is to identify key genes and pathways that drive tumor pathogenesis. Although many studies have identified candidate driver genes based on recurrence of mutations in individual genes, subsets of genes with nonrecurrent mutations may also be defined as p...
  13. Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma.

    Science 344(6190):1396 (2014) PMID 24925914 PMCID PMC4123637

    Human cancers are complex ecosystems composed of cells with distinct phenotypes, genotypes, and epigenetic states, but current models do not adequately reflect tumor composition in patients. We used single-cell RNA sequencing (RNA-seq) to profile 430 cells from five primary glioblastomas, which ...
  14. Single-cell RNA-seq reveals dynamic paracrine control of cellular variation.

    Nature 510(7505):363 (2014) PMID 24919153 PMCID PMC4193940

    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 dendr...
  15. Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer.

    Nature Biotechnology 32(5):479 (2014) PMID 24752078 PMCID PMC4034575

    Comprehensive analyses of cancer genomes promise to inform prognoses and precise cancer treatments. A major barrier, however, is inaccessibility of metastatic tissue. A potential solution is to characterize circulating tumor cells (CTCs), but this requires overcoming the challenges of isolating ...
  16. Heterogeneity in immune responses: from populations to single cells.

    Trends in Immunology 35(5):219 (2014) PMID 24746883 PMCID PMC4035247

    The mammalian immune system is tasked with protecting the host against a broad range of threats. Understanding how immune populations leverage cellular diversity to achieve this breadth and flexibility, particularly during dynamic processes such as differentiation and antigenic response, is a co...
  17. Reconstructing and reprogramming the tumor-propagating potential of glioblastoma stem-like cells.

    Cell 157(3):580 (2014) PMID 24726434 PMCID PMC4004670

    Developmental fate decisions are dictated by master transcription factors (TFs) that interact with cis-regulatory elements to direct transcriptional programs. Certain malignant tumors may also depend on cellular hierarchies reminiscent of normal development but superimposed on underlying genetic...
  18. Preparation of Single-Cell RNA-Seq Libraries for Next Generation Sequencing.

    Current protocols in molecular biology / edited... 107:4.22.1 (2014) PMID 24984854 PMCID PMC4338574

    For the past several decades, due to technical limitations, the field of transcriptomics has focused on population-level measurements that can mask significant differences between individual cells. With the advent of single-cell RNA-Seq, it is now possible to profile the responses of individual ...
  19. Single-cell transcriptomics reveals bimodality in expression and splicing in immune cells.

    Nature 498(7453):236 (2013) PMID 23685454 PMCID PMC3683364

    Recent molecular studies have shown that, even when derived from a seemingly homogenous population, individual cells can exhibit substantial differences in gene expression, protein levels and phenotypic output, with important functional consequences. Existing studies of cellular heterogeneity, h...
  20. Dynamic regulatory network controlling TH17 cell differentiation.

    Nature 496(7446):461 (2013) PMID 23467089 PMCID PMC3637864

    Despite their importance, the molecular circuits that control the differentiation of naive T cells remain largely unknown. Recent studies that reconstructed regulatory networks in mammalian cells have focused on short-term responses and relied on perturbation-based approaches that cannot be read...