title: Dissecting Embryonic Stem Cell Self-Renewal and Differentiation Commitment from Quantitative Models.
abstract: To model quantitatively embryonic stem cell (ESC) self-renewal and differentiation by computational approaches, we developed a unified mathematical model for gene expression involved in cell fate choices. Our quantitative model comprised ESC master regulators and lineage-specific pivotal genes. It took the factors of multiple pathways as input and computed expression as a function of intrinsic transcription factors, extrinsic cues, epigenetic modifications, and antagonism between ESC master regulators and lineage-specific pivotal genes. In the model, the differential equations of expression of genes involved in cell fate choices from regulation relationship were established according to the transcription and degradation rates. We applied this model to the Murine ESC self-renewal and differentiation commitment and found that it modeled the expression patterns with good accuracy. Our model analysis revealed that Murine ESC was an attractor state in culture and differentiation was predominantly caused by antagonism between ESC master regulators and lineage-specific pivotal genes. Moreover, antagonism among lineages played a critical role in lineage reprogramming. Our results also uncovered that the ordered expression alteration of ESC master regulators over time had a central role in ESC differentiation fates. Our computational framework was generally applicable to most cell-type maintenance and lineage reprogramming.
authors: 1 School of Electronics and Information Technology, Sun Yat-Sen University , Higher Education Mega Center, Guangzhou, China .|2 Department of Applied Mathematics, Guangdong University of Finance , Longdong, Guangzhou, China .
authors: Rong
authors: R
authors: Hu
authors: 1 School of Electronics and Information Technology, Sun Yat-Sen University , Higher Education Mega Center, Guangzhou, China .
authors: Xianhua
authors: X
authors: Dai
authors: 3 School of Data and Computer Science, Sun Yat-Sen University, Higher Education Mega Center, Guangzhou, China .
authors: Zhiming
authors: Z
authors: Dai
authors: 1 School of Electronics and Information Technology, Sun Yat-Sen University , Higher Education Mega Center, Guangzhou, China .
authors: Qian
authors: Q
authors: Xiang
authors: 1 School of Electronics and Information Technology, Sun Yat-Sen University , Higher Education Mega Center, Guangzhou, China .
authors: Yanning
authors: Y
authors: Cai
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000166:cytology*; D051379:Mice; D008954:Models, Biological; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: D014157:Transcription Factors
keywords: cell fate choices; embryonic stem cell; epigenetic modifications; gene expression; lineage antagonism; quantitative models