The paper introduces CEL-Seq2, an improved version of the CEL-Seq method for single-cell RNA-Seq. CEL-Seq2 offers threefold higher sensitivity, lower costs, and reduced hands-on time compared to its predecessor. The method was implemented on Fluidigm’s C1 system, enabling on-chip barcoding and detecting gene expression changes during the cell cycle in mouse fibroblast cells. The authors compared CEL-Seq2 with Smart-Seq, demonstrating its increased sensitivity. Key improvements include optimized primers, reagents, clean-up, and library preparation steps, which enhance data quality and efficiency. CEL-Seq2 is also compatible with different platforms, such as the Fluidigm C1, and shows better sensitivity and reproducibility than Smart-Seq. The study concludes that CEL-Seq2 is a highly sensitive and cost-effective method for single-cell RNA-Seq analysis.The paper introduces CEL-Seq2, an improved version of the CEL-Seq method for single-cell RNA-Seq. CEL-Seq2 offers threefold higher sensitivity, lower costs, and reduced hands-on time compared to its predecessor. The method was implemented on Fluidigm’s C1 system, enabling on-chip barcoding and detecting gene expression changes during the cell cycle in mouse fibroblast cells. The authors compared CEL-Seq2 with Smart-Seq, demonstrating its increased sensitivity. Key improvements include optimized primers, reagents, clean-up, and library preparation steps, which enhance data quality and efficiency. CEL-Seq2 is also compatible with different platforms, such as the Fluidigm C1, and shows better sensitivity and reproducibility than Smart-Seq. The study concludes that CEL-Seq2 is a highly sensitive and cost-effective method for single-cell RNA-Seq analysis.