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Conventional CRISPR knockout screens target genes via focal indels that readily disrupt open reading frames (ORFs). However, their utility for targeting candidate cis-regulatory elements remains limited, as focal indels cannot abrogate enhancer activity with high confidence. Compounding this limitation, conventional CR...
A lineage-resolved view of embryogenesis reveals that cell identity alone predicts neither developmental ancestry nor the timing of fate restriction, and builds FateVec, an analysis framework that infers fate-bias dynamics and lineage-associated transcriptional programs from reconstructed phylogenies.
Mammalian biology unfolds over time, within tissues and organs opaque to our eyes and instruments. We applied DNA Typewriter, a sequential molecular recorder, to record the cell lineage of a mouse over nearly two weeks of development. From one embryo, we reconstruct a time-calibrated, parsimony-supported, zygote-rooted...
DNA Typewriter, a sequential molecular recorder, was applied to record the cell lineage of a mouse over nearly two weeks of development, reconstructing a time-calibrated, parsimony-supported, zygote-rooted phylogeny of 1.28M transcriptionally-profiled cells.
Intrinsic, heritable fluctuations in mESC state are an important source of organoid heterogeneity, and DNA Typewriter enables high-resolution lineage trees in stem cell models.
The complete cell lineage of C. elegans, mapped over four decades ago, was tractable because the animal is small, transparent, and lineage invariant1. Most animals are none of these, having orders of magnitude more cells, being opaque, and developing with substantial stochasticity2. Since 2016, genome editing-based lin...
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