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Spatiotemporally resolved transcriptomics reveals the subcellular RNA kinetic landscape.
Ren, Jingyi; Zhou, Haowen; Zeng, Hu; Wang, Connie Kangni; Huang, Jiahao; Qiu, Xiaojie; Sui, Xin; Li, Qiang; Wu, Xunwei; Lin, Zuwan; Lo, Jennifer A; Maher, Kamal; He, Yichun; Tang, Xin; Lam, Judson; Chen, Hongyu; Li, Brian; Fisher, David E; Liu, Jia; Wang, Xiao.
Afiliação
  • Ren J; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Zhou H; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Zeng H; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Wang CK; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Huang J; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Qiu X; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Sui X; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Li Q; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Wu X; Whitehead Institute for Biomedical Research Cambridge, Cambridge, MA, USA.
  • Lin Z; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Lo JA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Maher K; John A. Paulson School of Engineering and Applied Sciences, Harvard University, Boston, MA, USA.
  • He Y; Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
  • Tang X; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Lam J; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
  • Chen H; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Li B; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Fisher DE; Computational and Systems Biology Program, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Liu J; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Wang X; John A. Paulson School of Engineering and Applied Sciences, Harvard University, Boston, MA, USA.
Nat Methods ; 20(5): 695-705, 2023 05.
Article em En | MEDLINE | ID: mdl-37038000
ABSTRACT
Spatiotemporal regulation of the cellular transcriptome is crucial for proper protein expression and cellular function. However, the intricate subcellular dynamics of RNA remain obscured due to the limitations of existing transcriptomics methods. Here, we report TEMPOmap-a method that uncovers subcellular RNA profiles across time and space at the single-cell level. TEMPOmap integrates pulse-chase metabolic labeling with highly multiplexed three-dimensional in situ sequencing to simultaneously profile the age and location of individual RNA molecules. Using TEMPOmap, we constructed the subcellular RNA kinetic landscape in various human cells from transcription and translocation to degradation. Clustering analysis of RNA kinetic parameters across single cells revealed 'kinetic gene clusters' whose expression patterns were shaped by multistep kinetic sculpting. Importantly, these kinetic gene clusters are functionally segregated, suggesting that subcellular RNA kinetics are differentially regulated in a cell-state- and cell-type-dependent manner. Spatiotemporally resolved transcriptomics provides a gateway to uncovering new spatiotemporal gene regulation principles.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: RNA / Transcriptoma Limite: Humans Idioma: En Revista: Nat Methods Assunto da revista: TECNICAS E PROCEDIMENTOS DE LABORATORIO Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: RNA / Transcriptoma Limite: Humans Idioma: En Revista: Nat Methods Assunto da revista: TECNICAS E PROCEDIMENTOS DE LABORATORIO Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos