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David A Hess, Katherine M Strelau, Anju Karki, Mei Jiang, Ana C Azevedo-Pouly, Ann-Hwee Lee, Tye G Deering, Chinh Q Hoang, Raymond J MacDonald, Stephen F Konieczny
Transcriptional networks that govern secretory cell specialization, including instructing cells to develop a unique cytoarchitecture, amass extensive protein synthesis machinery, and be embodied to respond to endoplasmic reticulum (ER) stress, remain largely uncharacterized. In this study, we discovered that the secretory cell transcription factor MIST1 (Bhlha15), previously shown to be essential for cytoskeletal organization and secretory activity, also functions as a potent ER stress-inducible transcriptional regulator...
September 19, 2016: Molecular and Cellular Biology
Padma Pradeepa Srinivasan, Vaishali N Patel, Shuang Liu, Daniel A Harrington, Matthew P Hoffman, Xinqiao Jia, Robert L Witt, Mary C Farach-Carson, Swati Pradhan-Bhatt
: : Radiotherapy for head and neck cancer often has undesirable effects on salivary glands that lead to xerostomia or severe dry mouth, which can increase oral infections. Our goal is to engineer functional, three-dimensional (3D) salivary gland neotissue for autologous implantation to provide permanent relief. An immediate need exists to obtain autologous adult progenitor cells as the use of embryonic and induced pluripotent stem cells potentially pose serious risks such as teratogenicity and immunogenic rejection...
August 18, 2016: Stem Cells Translational Medicine
Benjamin D Moore, Shradha S Khurana, Won Jae Huh, Jason C Mills
We have previously shown that the sequential transcription factors Xbp1→Mist1 (Bhlha15) govern the ultrastructural maturation of the secretory apparatus in enzyme-secreting zymogenic chief cells (ZCs) in the gastric unit. Here we sought to identify transcriptional regulators upstream of X-box binding protein 1 (XBP1) and MIST1. We used immunohistochemistry to characterize Hnf4α(flox/flox) adult mouse stomachs after tamoxifen-induced deletion of Hnf4α We used qRT-PCR, Western blotting, and chromatin immunoprecipitation to define the molecular interaction between hepatocyte nuclear factor 4 alpha (HNF4α) and Xbp1 in mouse stomach and human gastric cells...
August 1, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
Michael A Hale, Galvin H Swift, Chinh Q Hoang, Tye G Deering, Toshi Masui, Youn-Kyoung Lee, Jumin Xue, Raymond J MacDonald
The orphan nuclear receptor NR5A2 is necessary for the stem-like properties of the epiblast of the pre-gastrulation embryo and for cellular and physiological homeostasis of endoderm-derived organs postnatally. Using conditional gene inactivation, we show that Nr5a2 also plays crucial regulatory roles during organogenesis. During the formation of the pancreas, Nr5a2 is necessary for the expansion of the nascent pancreatic epithelium, for the subsequent formation of the multipotent progenitor cell (MPC) population that gives rise to pre-acinar cells and bipotent cells with ductal and islet endocrine potential, and for the formation and differentiation of acinar cells...
August 2014: Development
Ramon U Jin, Jason C Mills
As they mature, professional secretory cells like pancreatic acinar and gastric chief cells induce the transcription factor MIST1 (also known as BHLHA15) to substantially scale up production of large secretory granules in a process that involves expansion of apical cytoplasm and redistribution of lysosomes and mitochondria. How a scaling factor like MIST1 rearranges cellular architecture simply by regulating expression levels of its transcriptional targets is unknown. RAB26 is a MIST1 target whose role in MIST1-mediated secretory cell maturation is also unknown...
March 1, 2014: Journal of Cell Science
Charis L Johnson, Jodi M Peat, Sonia N Volante, Rennian Wang, Carolyn A McLean, Christopher L Pin
Pancreatic ductal adenocarcinoma (PDAC) has a 5 year survival rate post-diagnosis of < 5%. Individuals with chronic pancreatitis (CP) are 20-fold more likely to develop PDAC, making it a significant risk factor for PDAC. While the relationship for the increased susceptibility to PDAC is unknown, loss of the acinar cell phenotype is common to both pathologies. Pancreatic acinar cells can dedifferentiate or trans-differentiate into a number of cell types including duct cells, β cells, hepatocytes and adipocytes...
November 2012: Journal of Pathology
Jason C Mills, Paul H Taghert
Developing cells acquire mature fates in part by selective (i.e. qualitatively different) expression of a few cell-specific genes. However, all cells share the same basic repertoire of molecular and subcellular building blocks. Therefore, cells must also specialize according to quantitative differences in cell-specific distributions of those common molecular resources. Here we propose the novel hypothesis that evolutionarily-conserved transcription factors called scaling factors (SFs) regulate quantitative differences among mature cell types...
January 2012: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
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