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Status |
Public on Jul 07, 2024 |
Title |
Temporal recording of mammalian development and precancer [rna-seq] |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Insights into many biological phenomena requires knowing the temporal order of cellular events, which is traditionally achieved through continuous direct observations [1, 2]. An alternative solution leverages irreversible genetic changes, such as naturally occurring mutations, to create indelible markers that enables retrospective temporal ordering [3-8]. Using Native sgRNA Capture and sequencing (NSC-seq), a newly devised and validated multi-purpose single-cell CRISPR platform, we developed a molecular clock approach to record the timing of cellular events and clonality in vivo while incorporating cell state and lineage information. Using this approach, we uncovered precise timing of tissue-specific cell expansion during murine embryonic development, unconventional developmental relationships between cell types, and new epithelial progenitor states by their unique genetic histories. NSC-seq analysis of murine adenomas coupled to multi-omic and single-cell profiling of human precancers, with clonal analysis of 418 human polyps, demonstrated the occurrence of polyancestral initiation in 15-30% of colonic precancers, revealing their origins from multiple normal founders. Our study presents a multimodal framework that lays the foundation for in vivo recording, integrating synthetic or natural indelible genetic changes with single-cell analyses to explore the origins and timing of development and tumorigenesis in mammalian systems.
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Overall design |
Mouse embryonic tissues and mouse intestinal epithelial (duodenum) tissues were dissociated using standard tissue dissociation procedues (methods section of the study). Cultured cell lines were also dissociated into single cells using TrypLE (Invitrogen). Dissociated single cells were encapsulated in a custom scRNA-seq (NSC-seq) platform.
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Contributor(s) |
Islam M, Lau K |
Citation missing |
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Submission date |
Jun 14, 2023 |
Last update date |
Jul 07, 2024 |
Contact name |
Mirazul Islam |
E-mail(s) |
md.mirazul.islam@vanderbilt.edu
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Phone |
8577538729
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Organization name |
Vanderbilt University
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Department |
Cell and Developmental Biology
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Lab |
Ken Lau
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Street address |
2213 Garland Ave
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City |
Nashville |
State/province |
TN |
ZIP/Postal code |
37232 |
Country |
USA |
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Platforms (1) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (10)
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This SubSeries is part of SuperSeries: |
GSE235119 |
Temporal recording of mammalian development and precancer |
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Relations |
BioProject |
PRJNA983786 |
Supplementary data files not provided |
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Raw data are available in SRA |
Processed data provided as supplementary file |
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