Uncovering the Quantitative Relationships Among Chromosome Fluctuations, Epigenetics, and Gene Expressions of Transdifferentiation on Waddington Landscape. Issue 10 (1st February 2022)

• Record Type: Journal Article
• Authors: Chu, Wen‐Ting; Chu, Xiakun; Wang, Jin
• Is Part Of: Advanced science. Volume 9:Issue 10(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-02-01
• Subjects: chromosome fluctuations -- epigenetics -- transdifferentiation -- Waddington landscape; Science -- Periodicals; 505
• DOI: 10.1002/advs.202103617
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: The 3D spatial organization of the chromosomes appears to be linked to the gene function, which is cell type‐specific. The chromosome structural ensemble switching model (CSESM) is developed by employing a heteropolymer model on different cell types and the important quantitative relationships among the chromosome ensemble, the epigenetic marks, and the gene expressions are uncovered, that both chromosome fluctuation and epigenetic marks have strong linear correlations with the gene expressions. The results support that the two compartments have different behaviors, corresponding to the relatively sparse and fluctuating phase (compartment A) and the relatively dense and stable phase (compartment B). Importantly, through the investigation of the transdifferentiation processes between the peripheral blood mononuclear cell (PBMC) and the bipolar neuron (BN), a quantitative description for the transdifferentiation is provided, which can be linked to the Waddington landscape. In addition, compared to the direct transdifferentiation between PBMC and BN, the transdifferentiation via the intermediate state neural progenitor cell (NPC) follows a different path (an "uphill" followed by a "downhill"). These theoretical studies bridge the gap among the chromosome fluctuations/ensembles, the epigenetics, and gene expressions in determining the cell fate. Abstract : The chromosome has different phase behaviors on the two compartments A and B. It can be shown by the chromosome structural ensemble switching model that there is a quantitative relationship among gene expressions, epigenetics, and chromosome ensemble structural fluctuations. In transdifferentiation, the switch of epigenetic marks can have a significant effect on the chromosome structural ensemble and gene expression.