RT Journal Article SR Electronic T1 Rainbow-seq: combining cell lineage tracking with single-cell RNA sequencing in preimplantation embryos JF bioRxiv FD Cold Spring Harbor Laboratory SP 293134 DO 10.1101/293134 A1 Fernando Biase A1 Qiuyang Wu A1 Riccardo Calandrelli A1 Marcelo Rivas-Astroza A1 Shuigeng Zhou A1 Sheng Zhong YR 2018 UL http://biorxiv.org/content/early/2018/06/16/293134.abstract AB Single-cell RNA-seq experiments cannot record cell division history and therefore cannot directly connect intercellular differences at a later developmental stage to their progenitor cells. We developed Rainbow-seq to combine cell division lineage tracing with single-cell RNA-seq. With distinct fluorescent protein genes as lineage markers, Rainbow-seq enables each single-cell RNA-seq experiment to simultaneously read single-cell transcriptomes and decode the lineage marker genes. We traced the lineages deriving from each blastomere in two-cell mouse embryos and observed inequivalent contributions to the embryonic and abembryonic poles in 72% of the blastocysts evaluated. Rainbow-seq on four- and eight-cell embryos with lineage tracing triggered at two-cell stage exhibited remarkable transcriptome-wide differences between the two cell lineages at both stages, including genes involved in negative regulation of transcription and signaling. These data provide critical insights on cell fate choices in cleavage embryos. Rainbow-seq bridged a critical gap between cellular division history and single-cell RNA-seq assays.