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<p>Single-cell RNA sequencing inadequately predicts protein abundance, particularly for intracellular cytokines. We developed CIPHER-seq (Cytokine Intracellular Protein High-throughput Expression with RNA-sequencing), enabling simultaneous quantification of intracellular proteins and transcriptomes. This system provides five layers of analysis. CIPHER-seq matched commercial protocols in immune cell recovery while significantly reducing mitochondrial stress signatures. Applied to stimulated PBMCs, CIPHER-seq resolved robust cytokine induction and metabolic remodeling, establishing a streamlined platform for intracellular multimodal profiling.</p>

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CIPHER-seq enables intracellular multimodal profiling of cytokine responses in single immune cells

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月8日

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  • Avni Bhalgat,
  • Katarina Micin,
  • Maurizio Affer,
  • Ana C. Ayupe,
  • Isabella Gomez,
  • Jonathan H. Schatz,
  • Erietta Stelekati,
  • Sion Williams,
  • Krishna Komanduri,
  • Eric Wieder,
  • Emiliano Cocco,
  • Justin Taylor

摘要

Single-cell RNA sequencing inadequately predicts protein abundance, particularly for intracellular cytokines. We developed CIPHER-seq (Cytokine Intracellular Protein High-throughput Expression with RNA-sequencing), enabling simultaneous quantification of intracellular proteins and transcriptomes. This system provides five layers of analysis. CIPHER-seq matched commercial protocols in immune cell recovery while significantly reducing mitochondrial stress signatures. Applied to stimulated PBMCs, CIPHER-seq resolved robust cytokine induction and metabolic remodeling, establishing a streamlined platform for intracellular multimodal profiling.