RRC ID 80739
Author Xu W, Liu J, Qi H, Si R, Zhao Z, Tao Z, Bai Y, Hu S, Sun X, Cong Y, Zhang H, Fan D, Xiao L, Wang Y, Li Y, Du Z.
Title A lineage-resolved cartography of microRNA promoter activity in C. elegans empowers multidimensional developmental analysis.
Journal Nat Commun
Abstract Elucidating the expression of microRNAs in developing single cells is critical for functional discovery. Here, we construct scCAMERA (single-cell cartography of microRNA expression based on reporter assay), utilizing promoter-driven fluorescent reporters in conjunction with imaging and lineage tracing. The cartography delineates the transcriptional activity of 54 conserved microRNAs in lineage-resolved single cells throughout C. elegans embryogenesis. The combinatorial expression of microRNAs partitions cells into fine clusters reflecting their function and anatomy. Notably, the expression of individual microRNAs exhibits high cell specificity and divergence among family members. Guided by cellular expression patterns, we identify developmental functions of specific microRNAs, including miR-1 in pharynx development and physiology, miR-232 in excretory canal morphogenesis by repressing NHR-25/NR5A, and a functional synergy between miR-232 and miR-234 in canal development, demonstrating the broad utility of scCAMERA. Furthermore, integrative analysis reveals that tissue-specific fate determinants activate microRNAs to repress protein production from leaky transcripts associated with alternative, especially neuronal, fates, thereby enhancing the fidelity of developmental fate differentiation. Collectively, our study offers rich opportunities for multidimensional expression-informed analysis of microRNA biology in metazoans.
Volume 15(1)
Pages 2783
Published 2024-3-30
DOI 10.1038/s41467-024-47055-4
PII 10.1038/s41467-024-47055-4
PMID 38555276
PMC PMC10981687
MeSH Animals Caenorhabditis elegans / metabolism Cell Differentiation / genetics Cell Lineage / genetics Embryonic Development / genetics Gene Expression Regulation, Developmental MicroRNAs* / genetics MicroRNAs* / metabolism
C.elegans tm4468