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Mutations at arbitrarily sampled genomic positions are identified using next-generation sequencing and are used to infer the lineage of DNA damage–prone 'mutator' mouse cells in culture.

Adipocytes have been suggested to arise from prospective progenitors of endothelial or haematopoietic origin. Rödeheffer and colleagues use lineage tracing to rule out that this is the case for white adipocytes, and show that they instead arise from CD24⁺ cells that are characterized by the expression of PdgfR (platelet-derived growth factor receptor).

One of two papers showing the generation of haematopoietic stem cells (HSCs) from the ventral wall of the dorsal aorta in live zebrafish embryos. Here, combined fluorescent reporter transgenes, confocal time-lapse microscopy and flow cytometry identify and isolate the stepwise intermediates as aortic haemogenic endothelium transitions to nascent HSCs. HSCs generated from this haemogenic endothelium are the lineal founders of virtually all of the adult haematopoietic system.

DNA barcoding methods for the analysis of clonal heterogeneity in cancer have been limited in terms of throughput and practical requirements. Here, the authors develop SunCatcher, a rapid and sensitive barcoding approach for live single-cell clonal evolution analysis, and use this method to study breast cancer cell populations.

Zhao et al. use genetic lineage tracing to demonstrate that pancreatic endocrine and exocrine progenitor cells do not generate new beta cells, thus arguing against beta-cell neogenesis in the adult mouse pancreas.

Hepatocytes are highly specialized cells and their fate is determined by their position in the liver as either periportal or perivenous hepatocytes. Here, Pu et al. show through genetic lineage tracing for Mfsd2 that periportal hepatocytes proliferate and reprogram into pericentral hepatocytes during liver regeneration and injury.

Blanpain and colleagues use inducible genetic lineage tracing to identify and follow the progenitors responsible for the development of the prostate glandular epithelium. They find that multipotent progenitors are initially able to differentiate into the three lineages that make up the prostate, with a later switch to distinct pools of unipotent basal and luminal stem cells.

Rinkevich, Weissman and colleagues show that mesothelin-expressing cells from the mesothelium, an epithelial monolayer covering vertebrate cavities and internal organs, generate the fibroblasts and smooth muscle cells (FSMCs) essential for the development of internal organs. Using a genetic lineage tracing approach, they find that these cells participate in generating FSMCs and vasculature, with minimal contributions from neural crest or circulating cells.

Retroviral integration is used to mark clones in human embryonic stem cell cultures and clonal distribution is assessed after functionally testing the cells with different methods. Distinct subsets of clones are detected after in vitro differentiation versus teratoma formation in vivo.

A Cre-loxP–based technique allows triggering of heritable coexpression of a fluorescent marker along with any desired transgene, providing a versatile tool for clonal analysis of gene function in the zebrafish.

A set of computational and imaging approaches, called MARS-ALT, permits three-dimensional tracking of plant tissue development, including cell lineaging, at cellular resolution. It is applied to the study of floral development in Arabidopsis.

Organ fibrosis often leads to end-stage organ failure, but the origin of key profibrotic cell types is still unclear. Lucie Peduto and her colleagues have used genetic lineage tracing and pharmacological ablation techniques to show that ADAM12⁺ perivascular cells are a key source of profibrotic cells in acute skin and muscle injury in the mouse. They also show that knockdown of ADAM12 expression is beneficial, suggesting a possible therapeutic target for the treatment of fibrosis.

Novel methods for tracking the progeny of single cells involve prospective lineage tracing, in which DNA barcodes are introduced into single cells and tracked over time, or retrospective lineage tracing, in which somatic mutations are used as DNA barcodes. These methods improve our understanding of cell fates in development, cell differentiation and tissue regeneration.

In this Review, Sheth and Wang describe emerging synthetic biology approaches for using DNA as a memory device for recording cellular events, including the various methodological steps from detecting diverse signals, converting them into DNA alterations and reading out and interpreting the recorded information. Furthermore, they discuss potential applications as biotechnological and environmental biosensors.

This protocol describes an approach for pulse labeling of ventricular zone progenitors and their neuronal progeny in the developing brain. Labeled cells can be isolated and highlighted by FACS or immunohistochemistry.

In this Review, Mallat and colleagues critically evaluate the studies on the origin, fate and functions of vascular smooth muscle cells (VSMCs) in atherosclerosis, highlighting the importance of developmental origin, clonal expansion and plasticity of VSMCs cells in atherosclerosis and summarizing the roles of VSMCs and VSMC-derived cells in plaque development and progression.

Understanding developmental trajectories has recently been enabled by progress in modern lineage-tracing methods that combine genetic lineage analysis with omics-based characterization of cell states (particularly transcriptomes). In this Review, Wagner and Klein discuss the conceptual underpinnings, experimental strategies and analytical considerations of these approaches, as well as the biological insights gained.

This Review discusses the origins of squamous cell carcinoma (SCC), with a focus on skin, lung, oesophageal and head and neck cancer, and describes how oncogenic mutations and the cell of origin cooperate in determining the rise of SCC.

This Review covers recent technological developments to label and manipulate genes in selected populations of cells in Drosophila melanogaster. The Review is intended as a user guide to help with the selection of the best expression systems and clonal analysis techniques for developmental studies in the fly.

The persistent production of extracellular matrix during fibrosis leads to impaired organ function. Myofibroblasts are considered the predominant effector cell during fibrosis; however, the exact origin of myofibroblasts during kidney disease is widely debated. Here, the authors describe the evidence supporting the various potential origins of renal myofibroblasts as well as the techniques used to trace and identify these progenitor cells. They discuss the therapeutic methods that might prevent the transition of precursors to a myofibroblast phenotype, thereby inhibiting fibrosis.

This Review discusses how genetic lineage tracing can be used to quantify the behaviour of normal, preneoplastic and tumour cells in epithelia in transgenic mice. It also discusses some of the limitations of lineage tracing in mouse models of cancer.

Cédric Blanpain discusses the progress achieved in identifying and characterizing the cellular origins of different solid tumours in mouse models of skin, brain, breast, gut and lung cancer, using genetic lineage tracing approaches.

Lineage tracing is a sophisticated technique to track cellsin vivo. Here, Paola Romagnani and colleagues describe how lineage tracing can be used to track the fate of cells involved in renal development, pathophysiological changes and regeneration. The authors discuss considerations in selecting an appropriate reporter, promoter, and activating switch for lineage tracing experiments, and approaches to data interpretation.