Polyclonal-to-monoclonal transition in colorectal precancerous evolution.

Unravelling the origin and evolution of precancerous lesions is crucial for effectively preventing malignant transformation, yet our current knowledge remains limited. Here we used a base editor-enabled DNA barcoding system to comprehensively map single-cell phylogenies in mouse models of intestinal tumorigenesis induced by inflammation or loss of the Apc gene. Through quantitative analysis of high-resolution phylogenies including 260,922 single cells from normal, inflamed and neoplastic intestinal tissues, we identified tens of independent cell lineages undergoing parallel clonal expansions within each lesion.

Photoacoustic Tomography with Temporal Encoding Reconstruction (PATTERN) for cross-modal individual analysis of the whole brain.

Cross-modal analysis of the same whole brain is an ideal strategy to uncover brain function and dysfunction. However, it remains challenging due to the slow speed and destructiveness of traditional whole-brain optical imaging techniques. Here we develop a new platform, termed Photoacoustic Tomography with Temporal Encoding Reconstruction (PATTERN), for non-destructive, high-speed, 3D imaging of ex vivo rodent, ferret, and non-human primate brains.

Achieving single-cell-resolution lineage tracing in zebrafish by continuous barcoding mutations during embryogenesis.

Unraveling the lineage relationships of all descendants from a zygote is fundamental to advancing our understanding of developmental and stem cell biology. However, existing cell barcoding technologies in zebrafish lack the resolution to capture the majority of cell divisions during embryogenesis. A recently developed method, a substitution mutation-aided lineage-tracing system (SMALT), successfully reconstructed high-resolution cell phylogenetic trees for Drosophila melanogaster.

A statistical method for quantifying progenitor cells reveals incipient cell fate commitments.

Quantifying the number of progenitor cells that found an organ, tissue or cell population is of fundamental importance for understanding the development and homeostasis of a multicellular organism. Previous efforts rely on marker genes that are specifically expressed in progenitors. This strategy is, however, often hindered by the lack of ideal markers.

Mapping single-cell-resolution cell phylogeny reveals cell population dynamics during organ development.

Mapping the cell phylogeny of a complex multicellular organism relies on somatic mutations accumulated from zygote to adult. Available cell barcoding methods can record about three mutations per barcode, enabling only low-resolution mapping of the cell phylogeny of complex organisms. Here we developed SMALT, a substitution mutation-aided lineage-tracing system that outperforms the available cell barcoding methods in mapping cell phylogeny.

An instantaneous coalescent method insensitive to population structure.

Conventional coalescent inferences of population history make the critical assumption that the population under examination is panmictic. However, most populations are structured. This complicates the prevailing coalescent analyses and sometimes leads to inaccurate estimates.

Drivers of Mating Type Composition in Tetrahymena thermophila.

Sex offers advantages even in primarily asexual species. Some ciliates appear to utilize such reproductive strategy with many mating types. However, the factors determining the composition of mating types in the unicellular ciliate Tetrahymena thermophila are poorly understood, and this is further complicated by non-Mendelian determination of mating type in the offspring.

Decoupling gene functions from knockout effects by evolutionary analyses.

Genic functions have long been confounded by pleiotropic mutational effects. To understand such genetic effects, we examine HAP4, a well-studied transcription factor in that functions by forming a tetramer with HAP2, HAP3 and HAP5. Deletion of HAP4 results in highly pleiotropic gene expression responses, some of which are clustered in related cellular processes (clustered effects) while most are distributed randomly across diverse cellular processes (distributed effects).