Control of Cellular Differentiation Trajectories for Cancer Reversion

2024/12/11 by Jeong‐Ryeol Gong, Chun‐Kyung Lee, Hoon‐Min Kim +4 · 4 voices
Biochemistry, Genetics and Molecular Biology · Medicine · #Single-cell and spatial transcriptomics #Cancer Cells and Metastasis #Gene Regulatory Network Analysis

paper · pdf · doi:10.1002/advs.202402132

openalex publication_date 2024/12/11 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/03

Abstract

Cellular differentiation is controlled by intricate layers of gene regulation, involving the modulation of gene expression by various transcriptional regulators. Due to the complexity of gene regulation, identifying master regulators across the differentiation trajectory has been a longstanding challenge. To tackle this problem, a computational framework, single-cell Boolean network inference and control (BENEIN), is presented. Applying BENEIN to human large intestinal single-cell transcriptome data, MYB, HDAC2, and FOXA2 are identified as the master regulators whose inhibition induces enterocyte differentiation. It is found that simultaneous knockdown of these master regulators can revert colorectal cancer cells into normal-like enterocytes by synergistically inducing differentiation and suppressing malignancy, which is validated by in vitro and in vivo experiments.

Citations

• A scalable SCENIC workflow for single-cell gene regulatory network analysis
• Generalizing RNA velocity to transient cell states through dynamical modeling
• Extending support for mouse data in the Molecular Signatures Database (MSigDB)

Discussions

• A master switch to get cancer cells to revert back to normal Seems too good to be true, but a neat lab result. I prefer getting expert opinions rather than cheaply produced clickbait. As more scienti [bsky, 0 points, 0 comments]
• A question for the #RNA-Seq community: I found the approach of Gong and collegues of using a #boolean framework in order to detect trancription factor networks quiet interesting (BENEIN). However, I d [bsky, 0 points, 0 comments]
• doi.org/10.1002/advs... [bsky, 0 points, 0 comments]
• The main way solid cancers are reduced chemically is by killing rapidly dividing cells, with cancers being the most rapid. Now also immunotherapy (get body to help.) Here is some evidence that by tar [bsky, 0 points, 0 comments]

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