Dynamics of Cell Fate Decisions during Chemically Induced Multi-Lineage Trans-Differentiation at Single-Cell Level

Area of Science:

• Cell Biology
• Developmental Biology
• Chemical Biology

Background:

• Cell trans-differentiation allows manipulation of cell identity.
• Small molecules (SMs) offer a cost-effective method for inducing trans-differentiation.
• A comprehensive atlas of chemical-induced trans-differentiation across diverse cell fates is lacking.

Purpose of the Study:

• To investigate the mechanisms of chemical-induced cell trans-differentiation.
• To construct a single-cell atlas of the trans-differentiation process.
• To analyze the time-course trajectory of trans-differentiation into multiple cell lineages.

Main Methods:

• Induction of trans-differentiation using a small molecule cocktail (6TCF).
• Single-cell RNA sequencing to create a high-resolution atlas.
• Time-course analysis of cell fate transitions.

Main Results:

• Demonstrated trans-differentiation of mouse embryonic fibroblasts (MEFs) into epithelial, neural, XEN-like, and endothelial cells.
• Identified dynamic shifts in cellular entropy and cell cycle progression during fate transitions.
• Revealed high ribosomal gene expression as a common intermediate feature in trans-differentiation.

Conclusions:

• The study provides an in-depth single-cell atlas of chemical-induced trans-differentiation.
• Dynamic cellular changes, including entropy and cell cycle shifts, characterize trans-differentiation.
• High ribosomal gene expression is a conserved intermediate state in this process, offering insights into cell fate determination.