Paper - Review

DOI: 10.1038/s41587-019-0206-z

Abstract

Understanding ← complex tissues
→ requires → single-cell deconstruction of (gene regulation)
← with 1⃣ precision 2⃣ scale

Assess → the performance of (a massively parallel droplet-based method)
→ for mapping transposase-accessible chromatin
← in single cell ← using sequencing (scATAC-seq)

Apply → scATAC-seq
→ to obtain (chromatin profiles) ← for more than 200K single cells
← in 1⃣ human blood 2⃣ basal cell carcinoma

Application of scATAC-seq
→ enables
→ 1⃣ marker-free identification ← of (cell type specific → cis & trans-regulatory elements)
→ 2⃣ mapping of disease-associated enhancer activity
→ 3⃣ reconstruction of trajectories of (cellular differentiation)

Application of scATAC-seq
→ reveals → regulatory networks
← in 1⃣ malignant 2⃣ stromal 3⃣ immune cells
← in the tumor micro-environment

Analysis of scATAC-seq profiles
← from (serial tumor biopsies) → before & after programmed cell death protein 1 blockade
→ identifies (chromatin regulators) ← of therapy-responsive T-cell subset
→ reveals → a shared regulatory program
← that governs 1⃣ intratumoral CD8+ T-cell exhaustion 2⃣ CD4+ T follicular helper cell development

scATAC-seq
→ will enable → the unbiased discovery of (gene regulatory factors)
← across diverse biological systems

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