1. Root Regeneration Triggers an Embryo-like Sequence Guided by Hormonal Interactions.

    Cell 165(7):1721 (2016) PMID 27212234 PMCID PMC4912400

    Plant roots can regenerate after excision of their tip, including the stem cell niche. To determine which developmental program mediates such repair, we applied a combination of lineage tracing, single-cell RNA sequencing, and marker analysis to test different models of tissue reassembly. We sho...
  2. A Generic and Cell-Type-Specific Wound Response Precedes Regeneration in Planarians.

    Developmental Cell 35(5):632 (2015) PMID 26651295 PMCID PMC4817857

    Regeneration starts with injury. Yet how injuries affect gene expression in different cell types and how distinct injuries differ in gene expression remain unclear. We defined the transcriptomes of major cell types of planarians--flatworms that regenerate from nearly any injury--and identified 1...
  3. 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...
  4. Pathogen Cell-to-Cell Variability Drives Heterogeneity in Host Immune Responses

    Cell 163(2):523 (2015)

  5. 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...
  6. The Regulatory Factor ZFHX3 Modifies Circadian Function in SCN via an AT Motif-Driven Axis.

    Cell 162(3):607 (2015) PMID 26232227 PMCID PMC4537516

    We identified a dominant missense mutation in the SCN transcription factor Zfhx3, termed short circuit (Zfhx3(Sci)), which accelerates circadian locomotor rhythms in mice. ZFHX3 regulates transcription via direct interaction with predicted AT motifs in target genes. The mutant protein has a decr...
  7. A Genome-wide CRISPR Screen in Primary Immune Cells to Dissect Regulatory Networks.

    Cell 162(3):675 (2015) PMID 26189680 PMCID PMC4522370

    Finding the components of cellular circuits and determining their functions systematically remains a major challenge in mammalian cells. Here, we introduced genome-wide pooled CRISPR-Cas9 libraries into dendritic cells (DCs) to identify genes that control the induction of tumor necrosis factor (...
  8. 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...
  9. 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...
  10. Spatial reconstruction of single-cell gene expression data.

    Nature Biotechnology 33(5):495 (2015) PMID 25867923 PMCID PMC4430369

    Spatial localization is a key determinant of cellular fate and behavior, but methods for spatially resolved, transcriptome-wide gene expression profiling across complex tissues are lacking. RNA staining methods assay only a small number of transcripts, whereas single-cell RNA-seq, which measures...
  11. Immunogenetics. Dynamic profiling of the protein life cycle in response to pathogens.

    Science 347(6226):1259038 (2015) PMID 25745177 PMCID PMC4506746

    Protein expression is regulated by the production and degradation of messenger RNAs (mRNAs) and proteins, but their specific relationships remain unknown. We combine measurements of protein production and degradation and mRNA dynamics so as to build a quantitative genomic model of the differenti...
  12. Single-cell analysis reveals key roles for Bcl11a in regulating stem cell fate decisions.

    Genome Biology 16(1):199 (2015) PMID 26390863 PMCID PMC4576375

    Cell-cycle fluctuations drive significant transcriptomic heterogeneity in murine hematopoietic stem cells. Additionally, deletion of Bcl11a alters the regulation of hematopoietic stem cell quiescence, self-renewal, and fate choice.
  13. 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 ...
  14. Transcriptome-wide mapping reveals widespread dynamic-regulated pseudouridylation of ncRNA and mRNA.

    Cell 159(1):148 (2014) PMID 25219674 PMCID PMC4180118

    Pseudouridine is the most abundant RNA modification, yet except for a few well-studied cases, little is known about the modified positions and their function(s). Here, we develop Ψ-seq for transcriptome-wide quantitative mapping of pseudouridine. We validate Ψ-seq with spike-ins and de novo iden...
  15. Perturbation of m6A writers reveals two distinct classes of mRNA methylation at internal and 5' sites.

    Cell Reports 8(1):284 (2014) PMID 24981863 PMCID PMC4142486

    N6-methyladenosine (m6A) is a common modification of mRNA with potential roles in fine-tuning the RNA life cycle. Here, we identify a dense network of proteins interacting with METTL3, a component of the methyltransferase complex, and show that three of them (WTAP, METTL14, and KIAA1429) are req...
  16. 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...
  17. 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 ...
  18. 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...
  19. 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 ...
  20. High-resolution mapping reveals a conserved, widespread, dynamic mRNA methylation program in yeast meiosis.

    Cell 155(6):1409 (2013) PMID 24269006 PMCID PMC3956118

    N(6)-methyladenosine (m(6)A) is the most ubiquitous mRNA base modification, but little is known about its precise location, temporal dynamics, and regulation. Here, we generated genomic maps of m(6)A sites in meiotic yeast transcripts at nearly single-nucleotide resolution, identifying 1,308 put...