Single-cell data-driven mathematical model reveals possible molecular mechanisms of embryonic stem-cell differentiation
Embryonic development is widely studied due to its application in disease treatment. The published literature demonstrated that Krüppel-like factor 8(KLF8) plays an important role in modulating mesendoderm to definitive endoderm (DE) differentiation. However, it is not clear how KLF8 interacts with...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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AIMS Press
2019-06-01
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| Series: | Mathematical Biosciences and Engineering |
| Subjects: | |
| Online Access: | https://www.aimspress.com/article/doi/10.3934/mbe.2019294?viewType=HTML |
| _version_ | 1818201284257251328 |
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| author | Xiao Tu Qinran Zhang Wei Zhang Xiufen Zou |
| author_facet | Xiao Tu Qinran Zhang Wei Zhang Xiufen Zou |
| author_sort | Xiao Tu |
| collection | DOAJ |
| description | Embryonic development is widely studied due to its application in disease treatment. The published literature demonstrated that Krüppel-like factor 8(KLF8) plays an important role in modulating mesendoderm to definitive endoderm (DE) differentiation. However, it is not clear how KLF8 interacts with other key genes and affects the differentiation process. To qualitatively and quantitatively explore the molecular mechanisms of KLF8 during the differentiation of human embryonic stem cells (hESCs) in detail, we developed a mathematical model to describe the dynamics between KLF8 and two other significant genes, E-cadherin(CDH1) and Zinc-finger E-box-binding homeobox1(ZEB1). Based on the single-cell RNA-seq data, the model structure and parameters were obtained using particle swarm optimization (PSO). The bifurcation analysis and simulation results reveal that the system can exhibit a complex tristable transition, which corresponds to the three states of embryonic development at the single-cell level. We further predict that the novel important gene KLF8 promotes the formation of DE cells by reciprocal inhibition between CDH1 and KLF8 and promotion of the expression of ZEB1. These results may help to shed light on the biological mechanism in the differentiation process of hESCs. |
| first_indexed | 2024-12-12T02:51:06Z |
| format | Article |
| id | doaj.art-6488d803ca9247eba69de14c2ceb1aa5 |
| institution | Directory Open Access Journal |
| issn | 1551-0018 |
| language | English |
| last_indexed | 2024-12-12T02:51:06Z |
| publishDate | 2019-06-01 |
| publisher | AIMS Press |
| record_format | Article |
| series | Mathematical Biosciences and Engineering |
| spelling | doaj.art-6488d803ca9247eba69de14c2ceb1aa52022-12-22T00:40:53ZengAIMS PressMathematical Biosciences and Engineering1551-00182019-06-011655877589610.3934/mbe.2019294Single-cell data-driven mathematical model reveals possible molecular mechanisms of embryonic stem-cell differentiationXiao Tu0Qinran Zhang1Wei Zhang 2Xiufen Zou31. School of Mathematics and Statistics, Wuhan University, Wuhan, P. R. China1. School of Mathematics and Statistics, Wuhan University, Wuhan, P. R. China2. School of Science, East China Jiaotong University, Nanchang, P. R. China1. School of Mathematics and Statistics, Wuhan University, Wuhan, P. R. ChinaEmbryonic development is widely studied due to its application in disease treatment. The published literature demonstrated that Krüppel-like factor 8(KLF8) plays an important role in modulating mesendoderm to definitive endoderm (DE) differentiation. However, it is not clear how KLF8 interacts with other key genes and affects the differentiation process. To qualitatively and quantitatively explore the molecular mechanisms of KLF8 during the differentiation of human embryonic stem cells (hESCs) in detail, we developed a mathematical model to describe the dynamics between KLF8 and two other significant genes, E-cadherin(CDH1) and Zinc-finger E-box-binding homeobox1(ZEB1). Based on the single-cell RNA-seq data, the model structure and parameters were obtained using particle swarm optimization (PSO). The bifurcation analysis and simulation results reveal that the system can exhibit a complex tristable transition, which corresponds to the three states of embryonic development at the single-cell level. We further predict that the novel important gene KLF8 promotes the formation of DE cells by reciprocal inhibition between CDH1 and KLF8 and promotion of the expression of ZEB1. These results may help to shed light on the biological mechanism in the differentiation process of hESCs.https://www.aimspress.com/article/doi/10.3934/mbe.2019294?viewType=HTMLembryonic stem cells(escs)single-cell databifurcationmolecular mechanismstristability |
| spellingShingle | Xiao Tu Qinran Zhang Wei Zhang Xiufen Zou Single-cell data-driven mathematical model reveals possible molecular mechanisms of embryonic stem-cell differentiation Mathematical Biosciences and Engineering embryonic stem cells(escs) single-cell data bifurcation molecular mechanisms tristability |
| title | Single-cell data-driven mathematical model reveals possible molecular mechanisms of embryonic stem-cell differentiation |
| title_full | Single-cell data-driven mathematical model reveals possible molecular mechanisms of embryonic stem-cell differentiation |
| title_fullStr | Single-cell data-driven mathematical model reveals possible molecular mechanisms of embryonic stem-cell differentiation |
| title_full_unstemmed | Single-cell data-driven mathematical model reveals possible molecular mechanisms of embryonic stem-cell differentiation |
| title_short | Single-cell data-driven mathematical model reveals possible molecular mechanisms of embryonic stem-cell differentiation |
| title_sort | single cell data driven mathematical model reveals possible molecular mechanisms of embryonic stem cell differentiation |
| topic | embryonic stem cells(escs) single-cell data bifurcation molecular mechanisms tristability |
| url | https://www.aimspress.com/article/doi/10.3934/mbe.2019294?viewType=HTML |
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