[ExI] Reprogramming cancer cells
Stuart LaForge
avant at sollegro.com
Sun Dec 29 05:04:19 UTC 2024
These researchers at the bioengineering departments at the Korea
Advanced Institute of Science and Technology used computational biology
techniques to develop a Boolean model of gene regulatory networks in
cells they call BENEIN. They then used it on human large intestinal
single-cell transcriptome data to identify three genes MYB, HDAC2, and
FOXA2 as "master regulatory genes" for differentiation into normal
intestinal cells. Then they claim that they took three different colon
cancer cell lines and by knocking down, i.e. shutting off those three
genes, made the cancer cells back phenotypically normal large intestine
cells.
https://onlinelibrary.wiley.com/doi/10.1002/advs.202402132
---------Excerpt------------------
Control of Cellular Differentiation Trajectories for Cancer Reversion
Jeong-Ryeol Gong, Chun-Kyung Lee, Hoon-Min Kim, Juhee Kim, Jaeog Jeon,
Sunmin Park,and Kwang-Hyun Cho*
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.
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Note that that they use "in vivo" in a biochemical sense which means
inside a living cell and not medical "in vivo" which means inside an
intact organism like a mouse or human.
Stuart LaForge
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