SPECIAL ISSUE ON DEVELOPMENT AT THE SINGLE CELL LEVEL
Summary: This Spotlight explores emerging technologies that are enabling the systematic and unbiased quantification of cell identity, and how these efforts will enable the construction of high-resolution, dynamic cell atlases.
Summary: A review of recent breakthroughs in single cell dynamic lineage tracing, outlining experimental and computational challenges and discussing applications for developmental biology.
Summary: This Review describes the concepts and use of computational approaches to infer cellular trajectories from single cell expression data and discusses the applications of these approaches to the study of development and disease.
Summary: This Review highlights new technologies that can be used to analyze gene and protein expression at the single cell level, and at spatial and temporal resolution, providing mechanistic insights into development, regeneration and disease.
Summary: This Review highlights technical advances in single cell measurements of chromatin modifications, describing how these methods can be used to connect chromatin and gene expression, classify cell types, and study development and disease.
Summary: This Review discusses the recent discoveries using single cell analysis and cell-based reconstitution that have helped to uncover the sensing, processing and spatial distribution of signaling information in core intercellular communication pathways.
Heterogeneity of transposon expression and activation of the repressive network in human fetal germ cells
Summary: Expression of L1 transposons in germ cells of the human fetal testis is developmentally regulated and heterogeneous, and corresponds with upregulation of PIWI/piRNA repression machinery and accumulation of H3K9me3.
STEM CELLS AND REGENERATION
Neuro-mesodermal progenitors (NMPs): a comparative study between pluripotent stem cells and embryo-derived populations
Summary: Single cell analysis of mouse PSC in vitro-derived populations, using support vector machine-based comparison with embryo-derived cells, uncovers the origin and structure of neuro-mesodermal progenitors.
Summary: Multicolour clonal genetic lineage tracing, organoid cultures and scRNA-seq analyses demonstrate that Lgr5 marks a subpopulation of bipotent hepatoblasts that reside at the apex of the hierarchy of a heterogenous hepatoblast pool.
Summary: Live imaging of ERK activity reveals a cell lineage component to signalling strength and suggests the normal variation in ERK activity does not determine the rate of pluripotency exit.
Differential RA responsiveness directs formation of functionally distinct spermatogonial populations at the initiation of spermatogenesis in the mouse
Summary: Mammalian male germ cells in the postnatal testis regulate their cellular fates by differential responsiveness to the differentiation signal provided by retinoic acid.
Stochastic single cell migration leads to robust horizontal cell layer formation in the vertebrate retina
Summary: Long-term in vivo lightsheet imaging of a large cohort of HCs shows that cell cycle and migration parameters vary substantially before final positioning. This provides evidence that retinal lamination contains variable and stochastic elements.
Summary: Single cell mRNA profiling of pancreatic endocrine progenitor induction, specification and segregation using a novel Ngn3 reporter mouse line reveals signature genes that define lineage restriction towards specific endocrine subtypes.
Summary: Using single cell transcriptomics to inspect Pitx2 function in cardiac development and left-right cellular specification, this study characterizes all deviations in cell composition, cellular state and differentiation trajectories.
Single cell expression analysis reveals anatomical and cell cycle-dependent transcriptional shifts during heart development
Summary: Transcriptional analysis of single mouse cardiac cells reveals that cell cycle activity has a specific anatomical pattern, and a great influence on transcriptional shifts and heart development.
Summary: A combination of single cell transcriptomics and live cell imaging reveals multiple mechanisms by which cells experiencing spontaneous DNA damage are marginalised from normal development.
Summary: A stochastic differentiation programme shows stepwise separation of cell fate, with initiation of cell type-specific gene expression coupled to global transcriptome changes shared by all cells.
Defining developmental diversification of diencephalon neurons through single cell gene expression profiling
Summary: Single cell RNAseq analysis of the developing mouse diencephalon reveals cellular heterogeneity, developmental trajectories and genetic cascades associated with cellular diversification within the posterior forebrain.
Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord
Summary: Single cell analysis provides an unbiased classification of neural tube cell populations and their associated gene expression profiles, identifying co-regulated genes that mediate a temporal programme of neuronal subtype specification.
Summary: Transcriptomic single cell analysis of postnatal developing heart valves identifies novel cell populations and uncovers interstitial cell heterogeneity.
Control of Hox transcription factor concentration and cell-to-cell variability by an auto-regulatory switch
Summary: Preferentially repressing and activating isoforms of the Hox transcription factor Antennapedia elicit a developmental regulatory switch from auto-activation to auto-repression that increases concentration and suppresses cell-to-cell variability over time.
TECHNIQUES AND RESOURCES
Summary: A single cell roadmap that outlines in developmental time how cells progress from the ductal epithelium towards endocrine α- and β-cells.
Summary: Using single cell RNA-seq, novel cell populations are identified that are associated with fusion of the lip/primary palate, developing a model that predicts molecular and cellular behaviours during fusion.
Single cell analysis of the developing mouse kidney provides deeper insight into marker gene expression and ligand-receptor crosstalk
Summary: This single cell profile of the developing mouse kidney associates known and new signalling molecules and pathways with specific cell types, representing a roadmap to improve in vitro models of the developing kidney.
QuBiT: a quantitative tool for analyzing epithelial tubes reveals unexpected patterns of organization in the Drosophila trachea
Summary: Analysis of Drosophila tracheae by QuBiT, developed to quantify parameters of biological tubes, revealed unexpected phenomena, including multiple cell parameter gradients and supracellular organization of an apical marker.
Single cell analysis of adult mouse skeletal muscle stem cells in homeostatic and regenerative conditions
Summary: Single cell RNA sequencing of adult muscle stem cells and primary myoblasts from homeostatic or regenerating muscles identifies distinct clusters of cell types with partially overlapping but distinct transcriptional signatures.