The protein regulation to stem cell division

Stem cells themseves have many regulatory factors that may react to signals from outside world so as to adjust their proliferation and differentiation, including regulation of proteins with cell asymmetric division and control of gene expression of nuclear factor. In addition, the number of stem cell division before terminal differentiation of stem cells is also constrainted by intracellular regulatory factors. This is called endogenous regulation.

1. Intracellular protein regulation of stem cell division:

The differentiation of Stem cells can produce new stem cells or differentiated functional cells. This differentiation asymmetry is due to the unequal distribution of the cell's own components and other surroundings. Structural proteins of cells, in particular cytoskeletal component, is very important for the cell development. As in Drosophila ovary, the regulation of asymmetric stem cell division is a organelle called shrink body containing many regulatory proteins such as membrane contractile protein and cyclin A. The combination of the shrink body and spindle body determines the part of cell differentiation, thereby making the essential ingredients that maintain the stem cell traits remain in the progeny of stem cells.

2. The regulation of transcription factor:

In vertebrates, the regulation of transcription factors to stem cell differentiation is very important. For example, in the occurrence of embryonic stem cells, the transcription factor Oct4 is required. Oct4 is a transcription factor of mammalian early embryonic cell expression, and it induces the expression of the target gene product FGF-4 and other growth factors. It can regulate the further differentiation of stem cells and the surrounding trophoblast through making use of paracrine function of growth factor. If Oct4 deleted, mutant embryos only can develop to the blastocyst stage, while the internal cells can't develop into the inner cell mass. Besides, leukemia inhibitory factor (LIF) can promote cultured mouse ES cell self-renewal, but it has no effect on human adult stem cells, indicating that transcriptional regulation between different species is not entirely consistent. Another example is that the Tcf / Lef family of transcription factors is very important for the differentiation of epithelial stem cells. Tcf / Lef is intermediate medium of the Wnt signaling pathway. When formating transcriptional complex with the β-Catenin, Tcf / Lef can promote skin cells to turn into a pluripotent state and to differentiate into hair follicles. In the industry of biology, recombinant human protein technology is developing prosperously due to the findings above.

Chinese scientists release new findings of mTORC1 protein complex

Cells would strictly control their metabolic processes to reconcile their growth and nutritional status according to nutrient levels in the environment. mTORC1 (mammalian target of rapamycin complex) is responsible for the integration of environmental and intracellular signaling and is responsible for the regulation of cell growth. mTORC1 is similar to the generation of recombinant human protein. mTORC1 dysregulation is very common in cancer, diabetes and other human diseases.

Amino acids will make mTORC1 transfer to the lysosome and activate there. People used to think that this activation is dependent on the amino acid Rag small GTPase, Ragulator complexes and v-ATPase (vacuolar H + -adenosine triphosphatase).

Research team from Fudan University and the University of California recently found that different amino acids on the regulation of mTORC1 are not the same. Leucine mTORC1 activation requires Rag GTPase, but activation of glutamine does not depend on Rag GTPase. The results were published in journal Science on January 7, and the paper's corresponding author is famous scholar professor Kun-Liang Guan.

Professor Kun-Liang Guan is mainly engaged in signal transduction regulating cell growth and tumor cell biology. He has been awarded many honors including the "MacArthur Genius Award" in United States. He is now currently a professor at the University of California, San Diego (UCSD) Department of Pharmacy, Institute of Life Sciences, Zhejiang University jointly Dean, Fudan University Biomedical Institute for Genomic Research laboratory of molecular cell Biology and PI.

The researchers knocked out cells RagA and RagB, but glutamine still allows mTORC1 to transfer to lysosomes. The study shows that this process requires v-ATPase but not Ragulator. In addition, the researchers also found that glutamine-induced activation of mTORC1 needs Arf1 GTPase to play a role.

This study reveals an mTORC1 activation cascade which is not dependent on Rag GTPase, showing the specific amino acid differences in the regulation of mTORC1. The article points out that leucine needs RagA and RagB to activate mTORC1, while glutamine doesn't need them. This difference appears to be an evolutionarily conserved regulation.

There are many cancer cell lines show increase of mTORC1 activity, and the growth of cancer cells is highly dependent on glutamine. It can be seen that mTORC1 activation induced by glutamine plays an important role in the growth of normal cells and tumor cells, was also occupied in the study and development of recombinant mouse protein.