Paper - Review

DOI: 10.1038/s41588-022-01088-x

Abstract

❗: to chart 1⃣ cell composition 2⃣ cell state changes
→ that occur during (the transformation of healthy colon)
→ to pre-cancerous adenomas to CRC
∴ Generated 1⃣ single-cell chromatin accessibility profiles 2⃣ single-cell transcriptomes
← from 1K to 10K cells per samples
→ for 1⃣ 48 polyps 2⃣ 27 normal tissues 3⃣ 6 CRCs
← collected from patient

A large fraction ← of 1⃣ polyp 2⃣ CRC cells
→ exhibit a stem-like phenotype
∴ Define 1⃣ a continuum of epigenetic 2⃣ transcriptional changes
← occurring in these stem-like cells ← as they progress from homeostasis to CRC

❗: Advanced polyps
→ contain increasing number ← of 1⃣ stem-like cells 2⃣ regulatory T-cells 3⃣ a subtype of pre-cancer-associated fibroblasts

❗: observe 1⃣ T-cell exhaustion 2⃣ RUNX1-regulated cancer-associated fibroblasts 2⃣ increasing accessibility
← associated with HNF4A motifs ← in epithelia

DNA methylation changes ← in sporadic CRC
→ are strongly anti-correlated
← with accessibility changes along this continuum
∴ Identifying regulatory markers → for molecular staging of polyps

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