ArticleDevelopmental cell2022
Simultaneous cellular and molecular phenotyping of embryonic mutants using single-cell regulatory trajectories.
Article in Developmental cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Integrating genetic variation with deep learning provides context for variants impacting transcription factor binding during embryogenesis.Genome research · 2025Article
- Conserved transcription factors coordinate synaptic gene expression through repression.bioRxiv : the preprint server for biology · 2025Article
- Comprehensive Predictions of Mef2-Mediated Chromatin Loops, Which May Inhibit Ubx Binding by Blocking Low-Affinity Binding Sites.Journal of developmental biology · 2024Article
- Single-cell transcriptomics illuminates regulatory steps driving anterior-posterior patterning of Drosophila embryonic mesoderm.Cell reports · 2023Article
- The continuum ofScience (New York, N.Y.) · 2022Article
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Developmental progression and cellular diversity are largely driven by transcription factors (TFs); yet, characterizing their loss-of-function phenotypes remains challenging and often disconnected from their underlying molecular mechanisms. Here, we combine single-cell regulatory genomics with loss-of-function mutants to jointly assess both cellular and molecular phenotypes. Performing sci-ATAC-seq at eight overlapping time points during Drosophila mesoderm development could reconstruct the developmental trajectories of all major muscle types and reveal the TFs and enhancers involved. To systematically assess mutant phenotypes, we developed a single-nucleus genotyping strategy to process embryo pools of mixed genotypes. Applying this to four TF mutants could identify and quantify their characterized phenotypes de novo and discover new ones, while simultaneously revealing their regulatory input and mode of action. Our approach is a general framework to dissect the functional input of TFs in a systematic, unbiased manner, identifying both cellular and molecular phenotypes at a scale and resolution that has not been feasible before.
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