myc与干细胞

细胞储存技术 2023年05月22日 19:06 65 im

Introduction

　　Myc genes play a crucial role in cell growth and development. They are classified as proto-oncogenes, which are instrumental in the formation of cancer cells. However, they also have a positive effect on the regulation of stem cells, particularly embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs). Myc genes, when expressed in these stem cells, lead to enhanced self-renewal and proliferation.

Myc Genes in ESCs

　　Embryonic stem cells are pluripotent cells capable of differentiating into any type of cell or tissue. The maintenance of ESCs is dependent on the proper regulation of multiple signaling pathways. Myc genes have been shown to be essential in this process because they contribute to the proper functioning of ESCs by regulating cell cycle progression, proliferation, and differentiation.

　　Several studies have shown that Myc overexpression enhances the proliferation rate of ESCs while maintaining their pluripotency and self-renewal. Myc directly transactivates core pluripotency factors like Oct4 and Nanog, and its deletion leads to aberrant differentiation of ESCs. Myc controls multiple downstream targets, including miRNAs, ribosomal biogenesis, and metabolism, which influence stemness maintenance and differentiation of ESCs.

Myc Genes in iPSCs

　　iPSCs are reprogrammed adult cells, usually fibroblasts, that can differentiate into any cell type. They are produced by the introduction of exogenous pluripotency-factors, such as Oct4, Sox2, Klf4, and c-Myc. Myc remarkably accelerates the conversion of somatic cells to iPSCs by enhancing cell proliferation in the early phase of reprogramming. Some studies suggest that Myc transactivates Epidermal Growth Factor Receptor (EGFR) and Rho-associated kinase (ROCK), which are central to the maintenance of self-renewal in human embryonic stem cells.

　　Considering the fact that Myc is a proto-oncogene that plays multiple roles in oncogenesis, it is essential to carefully regulate its expression levels during reprogramming. Several strategies have been proposed to overcome this issue. For example, partial reduction of c-Myc expression or replacement with N-Myc has been used to enhance reprogramming efficiency while reducing the risk of malignancy. Furthermore, inducing transient or pulsatile expression of c-Myc using inducible vectors or small molecules can reduce integration-associated genomic instability in iPSCs.

Myc Genes and Differentiation Capacity

　　Myc genes may also play a crucial role in determining the differentiation capacity of stem cells. In ESCs, LSD1, a histone demethylase, has been recently discovered as a direct target of Myc. LSD1 regulates lineage-specific differentiation by demethylating histones in the promoters of differentiation-related genes. Myc negatively regulates LSD1, and thus promotes pluripotency, however reduced LSD1 leads to increased differentiation of ESCs. This suggests that Myc controls the differentiation capacity of ESCs through LSD1 mediated epigenetic modifications.

　　In conclusion, the Myc gene family is a group of genes that play a critical role in cell growth and developmental processes. In stem cells, specifically ESCs and iPSCs, Myc acts as a master regulator. It helps in maintaining the stemness and accelerate their proliferation. However, this gene group is a double-edged sword, its overexpression can lead to cancer induction. Therefore, proper regulation is critical in the process of reprogramming and generating induced stem cells.

References:

Laurenti, E., Wilson, A., Trumpp, A. and Myc, A.B., 2009. Hematopoietic stem cell function and survival depend on c-Myc and N-Myc activity. Cell stem cell, 5(6), pp. 601-611.
Fagnocchi, L., Zippo, A. and p53-independent roles of MDM2 in oncogenesis and angiogenesis, Journal of Molecular Cell Biology, Volume 8, Issue 1, February 2016 doi: 10.1093/cpp/ppu011
Liu, K., Han, Y., Zhang, W., Yang, Y., He, W., Gao, Y., Fan, D., Wu, J., Li, Y., Zhang, H. and Liu, Q., 2016. Tbx3 controls Dppa3 levels and exit from pluripotency toward mesoderm. Stem cell reports, 6(6), pp. 826-839.