Temporal recording of mammalian development and precancer
成果类型：
Article
署名作者：
Islam, Mirazul; Yang, Yilin; Simmons, Alan J.; Shah, Vishal M.; Musale, Krushna Pavan; Xu, Yanwen; Tasneem, Naila; Chen, Zhengyi; Trinh, Linh T.; Molina, Paola; Ramirez-Solano, Marisol A.; Sadien, Iannish D.; Dou, Jinzhuang; Rolong, Andrea; Chen, Ken; Magnuson, Mark A.; Rathmell, Jeffrey C.; Macara, Ian G.; Winton, Douglas J.; Liu, Qi; Zafar, Hamim; Kalhor, Reza; Church, George M.; Shrubsole, Martha J.; Coffey, Robert J.; Lau, Ken S.
署名单位：
Vanderbilt University; Vanderbilt University; Indian Institute of Technology System (IIT System); Indian Institute of Technology (IIT) - Kanpur; Vanderbilt University; Vanderbilt University; Vanderbilt University; Vanderbilt University; University of Cambridge; CRUK Cambridge Institute; Cancer Research UK; University of Texas System; UTMD Anderson Cancer Center; Vanderbilt University; Vanderbilt University; Vanderbilt University; Indian Institute of Technology System (IIT System); Indian Institute of Technology (IIT) - Kanpur; Johns Hopkins University; Harvard University; Harvard Medical School; Harvard University; Vanderbilt University; Vanderbilt University; Vanderbilt University; Vanderbilt University
刊物名称：
Nature
ISSN/ISSBN：
0028-4670
DOI：
10.1038/s41586-024-07954-4
发表日期：
2024-10-31
页码：
1187-1195
关键词：
clonal analysis
cancer
cells
endoderm
lineages
DYNAMICS
origin
INFORMATION
mutations
EVOLUTION
摘要：
Temporal ordering of cellular events offers fundamental insights into biological phenomena. Although this is traditionally achieved through continuous direct observations1,2, an alternative solution leverages irreversible genetic changes, such as naturally occurring mutations, to create indelible marks that enables retrospective temporal ordering3-5. Using a multipurpose, single-cell CRISPR platform, we developed a molecular clock approach to record the timing of cellular events and clonality in vivo, with incorporation of cell state and lineage information. Using this approach, we uncovered precise timing of tissue-specific cell expansion during mouse embryonic development, unconventional developmental relationships between cell types and new epithelial progenitor states by their unique genetic histories. Analysis of mouse adenomas, coupled to multiomic and single-cell profiling of human precancers, with clonal analysis of 418 human polyps, demonstrated the occurrence of polyclonal initiation in 15-30% of colonic precancers, showing 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. Using a multipurpose, single-cell CRISPR platform, we demonstrate precise timing of tissue-specific cell expansion during mouse embryonic development, unconventional developmental relationships between cell types, new epithelial progenitor states and insights into precancer initiation by leveraging genetic histories.