Control of Cellular Differentiation Trajectories for Cancer Reversion
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 longstan...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202402132 |
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| author | Jeong‐Ryeol Gong Chun‐Kyung Lee Hoon‐Min Kim Juhee Kim Jaeog Jeon Sunmin Park Kwang‐Hyun Cho |
| author_facet | Jeong‐Ryeol Gong Chun‐Kyung Lee Hoon‐Min Kim Juhee Kim Jaeog Jeon Sunmin Park Kwang‐Hyun Cho |
| author_sort | Jeong‐Ryeol Gong |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b86631ad535246b2b272f9981d6fcaef |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-b86631ad535246b2b272f9981d6fcaef2025-01-20T13:04:18ZengWileyAdvanced Science2198-38442025-01-01123n/an/a10.1002/advs.202402132Control of Cellular Differentiation Trajectories for Cancer ReversionJeong‐Ryeol Gong0Chun‐Kyung Lee1Hoon‐Min Kim2Juhee Kim3Jaeog Jeon4Sunmin Park5Kwang‐Hyun Cho6Department of Bio and Brain Engineering Korea Advanced Institute of Science and Technology Daejeon 34141 Republic of KoreaDepartment of Bio and Brain Engineering Korea Advanced Institute of Science and Technology Daejeon 34141 Republic of KoreaDepartment of Bio and Brain Engineering Korea Advanced Institute of Science and Technology Daejeon 34141 Republic of KoreaDepartment of Bio and Brain Engineering Korea Advanced Institute of Science and Technology Daejeon 34141 Republic of KoreaDepartment of Bio and Brain Engineering Korea Advanced Institute of Science and Technology Daejeon 34141 Republic of KoreaDepartment of Bio and Brain Engineering Korea Advanced Institute of Science and Technology Daejeon 34141 Republic of KoreaDepartment of Bio and Brain Engineering Korea Advanced Institute of Science and Technology Daejeon 34141 Republic of KoreaAbstract 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.https://doi.org/10.1002/advs.202402132Boolean gene regulatory network modelcancer reversioncell fate controlnetwork reconstructionsingle‐cell transcriptomesystems biology |
| spellingShingle | Jeong‐Ryeol Gong Chun‐Kyung Lee Hoon‐Min Kim Juhee Kim Jaeog Jeon Sunmin Park Kwang‐Hyun Cho Control of Cellular Differentiation Trajectories for Cancer Reversion Advanced Science Boolean gene regulatory network model cancer reversion cell fate control network reconstruction single‐cell transcriptome systems biology |
| title | Control of Cellular Differentiation Trajectories for Cancer Reversion |
| title_full | Control of Cellular Differentiation Trajectories for Cancer Reversion |
| title_fullStr | Control of Cellular Differentiation Trajectories for Cancer Reversion |
| title_full_unstemmed | Control of Cellular Differentiation Trajectories for Cancer Reversion |
| title_short | Control of Cellular Differentiation Trajectories for Cancer Reversion |
| title_sort | control of cellular differentiation trajectories for cancer reversion |
| topic | Boolean gene regulatory network model cancer reversion cell fate control network reconstruction single‐cell transcriptome systems biology |
| url | https://doi.org/10.1002/advs.202402132 |
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