http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Autophagy: A Critical Regulator of Cellular Metabolism and Homeostasis
Stefan W. Ryter,Suzanne M. Cloonan,Augustine M. K. Choi 한국분자세포생물학회 2013 Molecules and cells Vol.36 No.1
Autophagy is a dynamic process by which cytosolic mate-rial, including organelles, proteins, and pathogens, are sequestered into membrane vesicles called autopha-gosomes, and then delivered to the lysosome for degra-dation. By recycling cellular components, this process provides a mechanism for adaptation to starvation. The regulation of autophagy by nutrient signals involves a com- plex network of proteins that include mammalian target of rapamycin, the class III phosphatidylinositol-3 kinase/Be-clin 1 complex, and two ubiquitin-like conjugation systems. Additionally, autophagy, which can be induced by multiple forms of chemical and physical stress, including endo-plasmic reticulum stress, and hypoxia, plays an integral role in the mammalian stress response. Recent studies indicate that, in addition to bulk assimilation of cytosol, autophagy may proceed through selective pathways that target distinct cargoes to autophagosomes. The principle homeostatic functions of autophagy include the selective clearance of aggregated protein to preserve proteostasis, and the selective removal of dysfunctional mitochondria (mitophagy). Additionally, autophagy plays a central role in innate and adaptive immunity, with diverse functions such as regulation of inflammatory responses, antigen presen-tation, and pathogen clearance. Autophagy can preserve cellular function in a wide variety of tissue injury and disease states, however, maladaptive or pro-pathogenic outcomes have also been described. Among the many diseases where autophagy may play a role in-clude proteo-pathies which involve aberrant accumulation of proteins (e.g., neurodegenerative disorders), infectious diseases, and metabolic disorders such as diabetes and metabolic syndrome. Targeting the autophagy pathway and its regu-latory components may eventually lead to the develop-ment of therapeutics.
Genome-wide characterization of the routes to pluripotency
Hussein, Samer M. I.,Puri, Mira C.,Tonge, Peter D.,Benevento, Marco,Corso, Andrew J.,Clancy, Jennifer L.,Mosbergen, Rowland,Li, Mira,Lee, Dong-Sung,Cloonan, Nicole,Wood, David L. A.,Munoz, Javier,Midd Nature Publishing Group, a division of Macmillan P 2014 Nature Vol.516 No.7530
Somatic cell reprogramming to a pluripotent state continues to challenge many of our assumptions about cellular specification, and despite major efforts, we lack a complete molecular characterization of the reprograming process. To address this gap in knowledge, we generated extensive transcriptomic, epigenomic and proteomic data sets describing the reprogramming routes leading from mouse embryonic fibroblasts to induced pluripotency. Through integrative analysis, we reveal that cells transition through distinct gene expression and epigenetic signatures and bifurcate towards reprogramming transgene-dependent and -independent stable pluripotent states. Early transcriptional events, driven by high levels of reprogramming transcription factor expression, are associated with widespread loss of histone H3 lysine 27 (H3K27me3) trimethylation, representing a general opening of the chromatin state. Maintenance of high transgene levels leads to re-acquisition of H3K27me3 and a stable pluripotent state that is alternative to the embryonic stem cell (ESC)-like fate. Lowering transgene levels at an intermediate phase, however, guides the process to the acquisition of ESC-like chromatin and DNA methylation signature. Our data provide a comprehensive molecular description of the reprogramming routes and is accessible through the Project Grandiose portal at http://www.stemformatics.org.
Divergent reprogramming routes lead to alternative stem-cell states
Tonge, Peter D.,Corso, Andrew J.,Monetti, Claudio,Hussein, Samer M. I.,Puri, Mira C.,Michael, Iacovos P.,Li, Mira,Lee, Dong-Sung,Mar, Jessica C.,Cloonan, Nicole,Wood, David L.,Gauthier, Maely E.,Korn, Nature Publishing Group, a division of Macmillan P 2014 Nature Vol.516 No.7530
Pluripotency is defined by the ability of a cell to differentiate to the derivatives of all the three embryonic germ layers: ectoderm, mesoderm and endoderm. Pluripotent cells can be captured via the archetypal derivation of embryonic stem cells or via somatic cell reprogramming. Somatic cells are induced to acquire a pluripotent stem cell (iPSC) state through the forced expression of key transcription factors, and in the mouse these cells can fulfil the strictest of all developmental assays for pluripotent cells by generating completely iPSC-derived embryos and mice. However, it is not known whether there are additional classes of pluripotent cells, or what the spectrum of reprogrammed phenotypes encompasses. Here we explore alternative outcomes of somatic reprogramming by fully characterizing reprogrammed cells independent of preconceived definitions of iPSC states. We demonstrate that by maintaining elevated reprogramming factor expression levels, mouse embryonic fibroblasts go through unique epigenetic modifications to arrive at a stable, Nanog-positive, alternative pluripotent state. In doing so, we prove that the pluripotent spectrum can encompass multiple, unique cell states.