发育系统生物学与复杂网络视角 系列 (2)

Alterations of Gene Expression Profiles Before and After Cell Division
---- The most important problem of cell fate determination
Yong Peng

In this paper [1], its results reflect that tissue type, physical position, lineage identity and left–right symmetry, all of them combine to distinguish each individual cell from nearly all other cells. I think these influence factors are redundant, we only need to consider the profiles of all genes expression of the cells. If there are no any differences between the expression profiles of all genes of two cells, we should think that the two cells are identical ( 全同的), just like the identity principle of microparticles in quantum mechanics.

Why we can think they are identical for cells which no any alterations of their gene expression profiles? Any final phenotypes and functions of cell must be dependent on protein. Transcriptional level, post-transcriptional level, translational level and post-translational level regulation of gene expression, all of them only in order to eventually control the conformation, covalent structure, concentration and distribution (localization) of proteins to control their function. Nucleosome position, covalent modifications of histone and DNA, histone variants, ncRNA and its covalent modifications, all of them and other epigenetic regulation, controlling the function of proteins is their only ultimate goal. Above all, all life activities must be dependent on protein to be significant and affect phenotype and function of cell. If proteins of some cells are identical, means structure, distribution and concentration of their proteins are no any differences, we think that thesecells are identical. That is to say, “proteins and their structure, distribution and concentration” or proteomic is a complete representation of a cell, “proteins identity” and “cell identity” are equivalent.

Cell differentiation, transdifferentiation and reprogramming are processes of function and phenotype of cell. If there is no alteration of cell function, we think its cell fate is not change. So the key problem of cell fate determination is “proteins identity”. In spite of some scientists showed that reprogramming towards pluripotency in single heterokaryons is initiated without cell division or DNA replication [2]. But in most cases, cell division is required for cell fate change [3-7]. So we should consider alterations of gene expression profiles before and after cell division.

We suppose a cell was named cell-0 and it contains n different proteins (or n kinds of proteins), cell-0 was divided into two cells, cell-00 and cell-01 (Figure 1). If we know the interactions and concentrations of n different proteins of the cell-0, cell-00 and cell-01. Maybe we can predict the cell function accurately by using support vector machine or deep learning algorithms.

References
[1] John Isaac Murray, et al. (2012). Multidimensional regulation of gene expression in the C. elegans embryo. Genome research, 22(7), 1282-1294.
[2] Nidhi Bhutani, et al. (2009). Reprogramming towards pluripotency requires AID-dependent DNA demethylation. Nature, 463(7284), 1042-1047.
[3] Tomomi Tsubouchi, et al. (2013). DNA synthesis is required for reprogramming mediated by stem cell fusion. Cell, 152(4), 873-883.
[4] Sergio Ruiz, et al. (2011). A high proliferation rate is required for cell reprogramming and maintenance of human embryonic stem cell identity. Current Biology, 21(1), 45-52.
[5] Siim Pauklin, et al. (2013). The cell-cycle state of stem cells determines cell fate propensitys. Cell, 155(1), 135-147.
[6] Shahragim Tajbakhsh, et al. (2009). Asymmetric cell divisions and asymmetric cell fates. Annual Review of Cell and Developmental, 25, 671-699.
[7] Pierre Fichelson, et al. (2005). Cell cycle and cell-fate determination in Drosophila neural cell lineages. Trends in Genetics, 21(7), 413–420

是我的Developmental Biology track课程作业之一。