Cell Research

Numerous sequence-specific transcription factors (transcription factors, TFs) a combination of cross-regulatory network, these regulatory networks constitute the basis of the cells play a biological function. On September 5, the internationally renowned journal Cell Online published an article entitled Circuitry and Dynamics of the Washington University researchers transcription factor regulation network loop dynamics and organization of Human Transcription Factor Regulatory Networks research papers, reports principles. The researchers used genome in vivo DNaseI footprinting, 475 sequence-specific transcription factor found in 41 different cells and tissues, and then analyze the dynamics of these linkages. The study found that the transcription factor network with a high degree of cell selectivity, cell selectivity is driven by several factors, including in the control of cell identity unrecognized regulon. And, also identified a variety of widely expressed factors affect the transcriptional regulatory network. Shocking, the Although transcription factors inherent diversity, independent regulatory networks of all cell types converge with neural network like life. This study provides extensive description of the transcription factor regulatory network loop dynamics and organizational principles.

FGF-21 biological functions mainly as the metabolic regulation hungry, but also start a major regulator of ketone body production factor. Studies have shown that patients with a variety of diseases, including diabetes, blood levels of FGF-21 significantly increased. Long-term fasting induced mouse liver expression of FGF-21 protein by peroxisome proliferator-activated receptor (PPAR) alpha pathway significantly with peripheral FGF-21 levels, and thus promote adipose tissue lipolysis and fatty acid to The outer periphery of release of fatty acids in the liver and then absorbed and converted to ketones. Another study shows that the role of FGF21 fibroblast growth factor 21 may be assisted by inducing PPAR-γ activation factor (PGC) 1α to complete, which can stimulate liver gluconeogenesis, fatty acid oxidation and ketone body production. Recent studies have shown that, FGF-21 can induce liver secretes pancreatic lipase. Liver pancreatic lipase will be a substantial increase in the metabolic state of low energy, so the FGF-21 that may be involved in the regulation of the metabolic state of low energy. FGF-21 transgenic mice were fasted for 24 hours into the metabolic state of the low-energy, generate large amounts of ketones, and normal mice do not. In addition, FGF21 fibroblast growth factor 21 transgenic mice petite, weighing only 40% to 50% of the normal mice. Hunger mainly by the growth hormone / insulin-like growth factor 1 (GH/IGF-1) way to inhibit the growth and FGF-21 can be activated by reducing the signal transduction and transcription factor (STAT) 5 activation to significantly reduce serum IGF content Therefore, FGF-21 in the state of hunger by inhibiting the growth to save energy. Thiazole TZDs (TZD) can induce db / db mice white fat and 3T3-L1 fat cells FGF-21 The expression. Rosiglitazone and pioglitazone increase insulin sensitivity through PPAR-γ, and white adipose PPAR-γ can induce FGF-21 expression, therefore TZD FGF-21 may play a role. Interestingly, the existence of circadian rhythm: FGF-21 The expression of PPAR-α ligands injected mice night bezafibrate can significantly induced the FGF-21 expression, while the daytime injection does not appear to the performance. Meanwhile, such a regulatory role in the PPAR-α knockout mice did not show that induced the expression of FGF-21 circadian bezafibrate is effected by circadian reactive liver PPAR-α system to determine. Human FGF-21 has been reported. Fasted for 7 days after the blood content of FGF-21 increases, and in patients with hypertriglyceridemia vivo FGF21 fibroblast growth factor 21 content 2 times higher than normal, and will further increase after taking fenofibrate. These data show that fasting can induce the expression of the human FGF-21, which may be regulated by PPAR-α. Other studies have shown that obesity and type 2 diabetes in patients with FGF-21 levels were significantly increased, and fat, insulin and triglyceride levels were positively correlated, but negatively correlated with high density lipoprotein. In addition, the FGF-21 mRNA expression in subcutaneous fat and blood content of FGF-21 significantly correlated prompted adipose tissue may be one of the main source of the blood FGF-21. Recent studies show that non-alcoholic fatty liver disease, chronic kidney disease and coronary heart disease in patients with blood FGF-21 levels were also significantly elevated.

Human dendritic cells originated from hematopoietic stem cells (hemopoieticstemcell). DC source of two ways: ① myeloid stem cells in the GM-CSF stimulated to differentiate into DC called myeloid DC (myeloid dendritic cells, the MDC), also known DCl, monocytes and granulocytes have a common precursor cells; Langerhans cells (Langerhans cells, LCs), the mesothelial (or dermal) DCs, and monocyte-derived DCs ② derived from lymphoid stem cells, known as lymphoid the DC (Lymophiod dendritic cells, LDC ) or plasmacytoid DC (plasmacytoid dendritic cells, pIX ;), i.e., DC2, and a common precursor cells of T cells and NK cells. Although the number of dendritic cells (DC) less than 1% of peripheral blood mononuclear cells, but the surface has a rich antigen presenting molecules (MHC-Ⅰ and MHC-II), co-stimulatory factor the (CD80/B7-1 CD86 / B7-2, CD40, CD40L, etc.) and adhesion factor (ICAM-1, ICAM-2, ICAM-3, LFA-1, LFA-3, etc.), is a powerful professional antigen presenting cells (APC). DC has its own the immunostimulatory ability, found the only way to activate naive T cells are not sensitized APC.

The bone marrow mesenchymal stem cells (mesenchymal stem cells, MSC) is an important member of the family stem cells, derived from the development of the early mesoderm and ectoderm. MSC was originally found in the bone marrow, increasing people's attention because it has multiple differentiation potential, hematopoietic support and promote the implantation of stem cells, immune regulation and self-replication. Such as mesenchymal stem cells under the particular inducing conditions in vivo or in vitro, can differentiate into fat, bone, cartilage, muscle, tendon, ligament, nerve, liver, cardiac, endothelial and other tissue cells, continuous passage culture and cryopreservation still has multiple differentiation potential, can be used as an ideal seed cells for aging and lesions caused by tissue and organ damage repair. Bone marrow mesenchymal stem cells because of its wide range of sources, easy isolation and culture, and has strong differentiation potential and advantages of autologous transplantation, more and more scholars of all ages, is considered to be soon be introduced optimal clinical treatment stem cells . Mesenchymal stem cells in the bone marrow has the following advantages: Have a strong proliferation capability and multilineage differentiation potential, not only to differentiate into hematopoietic cells in a suitable in vivo or in vitro environments, and also having the differentiation of muscle cells, liver cells, osteoblasts, chondrocytes, and stromal cells variety the ability of the cells. Two immunomodulatory functions through the interaction between the cells and the to produce cytokines inhibit T cell proliferation and immune response, thus play the function of the immune reconstitution. Three. Has a convenient source of easy separation, culture, amplification and purification the multiple passages amplification still has the characteristics of stem cells, there is no immune rejection characteristics.

According to the American physicist organizational networks reported on June 29, U.S. scientists found cytokines SAMHD1 protein inhibition mechanism of bone marrow cells infected with HIV (the AIDS virus), new research extends the people how to evade the immune system of AIDS patients how to deal with HIV and HIV the understanding of the immune response in order to find to prevent HIV infection or to prevent the new therapies for its replication in the infected individuals. The research is published in the June 30 issue of Nature magazine. Bone marrow cells are the antigen a subset of the white blood cells, the immune response against viruses and other pathogens is very important for the body. Jack Scott the Jaworski's research team at Case Western Reserve University School of Medicine, AIDS Research Center and the Stowers Institute for Medical Research in the United States, Michael Walsh led a team SAMHD1 protein that senses such as macrophages and dendritic cells and bone marrow cells infected with HIV-1 virus (HIV divided into type 1 and type 2, type 1 is the main strains of the global epidemic of type 2 only popular in West Africa) and other immunodeficiency virus copies of the virus and prevent synthesis in these cells, thereby inhibiting the HIV virus. Previously, scientists have always thought that, SAMHD1 mutation can cause symptoms called AGS and symptoms of congenital infection, to be attributed to the absence of the virus, the immune system interferon inappropriate induction. Therefore, SAMHD1 and other the initiator the AGS cell proteins can abandon the nucleic acid fragments of the cells, and the prevention of such interferon system is activated inappropriately.