AST: Adherent-to-Suspension Transcriptomics
A TUCCA computational project using time-series transcriptomics to dissect the adherent-to-suspension transition (AST) — how cells adapt from anchored to free-floating growth, a key bottleneck for scaling cultivated meat.
The challenge
Section titled “The challenge”Scaling cultivated meat means growing large quantities of cells efficiently. Many research cell lines grow attached to a surface (adherent), but industrial production favours cells grown floating in suspension. The adherent→suspension transition is a complex biological process, and engineering it requires understanding the precise transcriptomic changes that let cells survive and thrive without attachment.
The computational approach
Section titled “The computational approach”Time-series RNA sequencing captured the transcriptional dynamics at five stages of
adaptation (n = 4 per timepoint). An early development version of
tucca-rna-seq served as the analytical engine —
quality control (FastQC, Qualimap), alignment (STAR), quantification (Salmon),
aggregation (MultiQC), differential expression (DESeq2), and functional enrichment
(clusterProfiler ORA/GSEA) — feeding custom downstream analyses including time-series
soft clustering (Mfuzz).
Key findings
Section titled “Key findings”- An acute, transient stress response at the point of transition (autophagy, MAPK signaling up; DNA replication down).
- Permanent reprogramming of suspension-adapted cells — suppressed metabolism and a committed, anchorage-independent adhesion profile.
- A proposed molecular mechanism for suspension proficiency: oxidative stress → MAPK p38δ → TEAD sequestration → a YAP–FoxO1 complex driving antioxidant production and adhesion-gene downregulation.
Read the paper
Section titled “Read the paper”Linked external resources are independent of TUCCA and Tufts University and remain under their own licenses.