Stem Cells & Wnt

Stem cells are the cells of origin. Stem cell is a cell that has the potential of proliferation and differentiation, and has the ability of self-renewing and replication, which can produce highly differentiated functional cells.

Stem cell has the following biological characteristics:
① the lifetime of stem cell biology remain undifferentiated or poorly differentiated characteristics;
② the number of stem cells in the body and the position is relatively constant;
③ Stem cell has self-renewal capacity;
④ Stem cell can proliferate unlimited;
⑤ The stem cells have the potential of multi-directional differentiation. They can differentiate into different types of tissue cells. Adult stem cells such as hematopoietic stem cells, mesenchymal stem cells, neural stem cells have certain cross lines, even across potential endoderm differentiation;
⑥ Stem cells divide slower cyclical characteristics, the vast majority of stem cells in the G0 phase;
⑦ Stem cells have two ways to divide, symmetric and asymmetric division split, the former forming two identical stem cells, and the latter form a stem cell and a progenitor cell.

According to differentiation of stem cells can be divided into totipotent stem cells, pluripotent stem cells and single stem cells. Totipotent stem cells can differentiate into any cell of the body, until the formation of a complex organism. Pluripotent stem cells can differentiate into various cell types, such as hematopoietic stem cells can differentiate into 12 kinds of blood cells.

Embryonic stem cells
According to the sequence of the individual development, the stem cells can be divided into embryonic stem cells and adult stem cells. Embryonic stem cells are pluripotent or totipotent cells, which are isolated from the inner cell mass or primordial germ cells of the embryo, in addition they can also be obtained by somatic cell nuclear transfer technology. ESC can express transcription factor Oct-3/4 of POU family; after transplantation, it can form a teratoma, which can be differentiated into somatic cells representing the three germ layer structure in vitro.

The use of ESC are as follows:
① Cloning animals, cloning animals from somatic cells as nuclear donors, although easy subjects, but the cloned animals showed severe physiological or immune deficiency, and mostly fatal;
② Transgenic animals, ESC cells as the carrier, can greatly accelerate the speed of production of genetically modified animals, improve the success rate;
③ Tissue engineering, artificial induction ESC directed differentiation, breed specific tissues and organs, for the purpose of medical treatment.

Wnt signaling pathway is a complex network of protein function, its function is most common in embryonic development and cancer, but is also involved in normal physiological processes in adult animals.

Discovery of Wnt signaling pathway
Wnt named after Wg (wingless) and Int. wingless gene was first discovered in Drosophila and act on embryonic development and in adult animal’s limb formation. INT gene was first found in vertebrates and is located near the integration site of mouse mammary tumor virus (MMTV). Int-1 gene and the wingless gene have homology.

Mutation of wingless gene in Drosophila can lead to non - wing deformity, MMTV replication and integration into the genome may lead to one or several Wnt genes increase i in mouse mammary tumors.

Mechanism of Wnt signaling pathway
Wnt signaling pathway comprises a number of proteins that regulate the synthesis of Wnt signaling molecules, which interact with the receptor on the target cell, and the physiological responses of the target cell are derived from the interaction of Wnt ligand between the cell and extracellular. Although the occurrence and intensity of the reaction due to Wnt ligands, cell types and the body itself, some components in the signal pathway, which are highly homologous from the nematode to human. The homology of proteins suggests that many Wnt ligands derived from different species are common ancestors of all living organisms.
Description of the canonical Wnt pathway: a series of reactions between Wnt protein and cell surface Frizzled receptor family binding, including the activation of the Dishevelled receptor family proteins and the final nuclearβ-actenin level changes.

Dishevelled (DSH) is a key component of the cell membrane associated Wnt receptor complex, which is activated after binding to Wnt, and inhibits downstream protein complexes, including axin, GSK-3 and APC protein. Axin / GSK-3 / APC complex can promote the degradation of intracellular signal molecule β-actenin. When the degradation of β-actenin complex is inhibited, β-actenin be stably present within the cytoplasm, and interact with TCF/LEF transcription factor families and promote the expression of specific genes.

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