keyword
MENU ▼
Read by QxMD icon Read
search

Arx AND pancreas

keyword
https://www.readbyqxmd.com/read/27243814/generation-of-functional-beta-like-cells-from-human-exocrine-pancreas
#1
Maria J Lima, Kenneth R Muir, Hilary M Docherty, Neil W A McGowan, Shareen Forbes, Yves Heremans, Harry Heimberg, John Casey, Kevin Docherty
Transcription factor mediated lineage reprogramming of human pancreatic exocrine tissue could conceivably provide an unlimited supply of islets for transplantation in the treatment of diabetes. Exocrine tissue can be efficiently reprogrammed to islet-like cells using a cocktail of transcription factors: Pdx1, Ngn3, MafA and Pax4 in combination with growth factors. We show here that overexpression of exogenous Pax4 in combination with suppression of the endogenous transcription factor ARX considerably enhances the production of functional insulin-secreting β-like cells with concomitant suppression of α-cells...
2016: PloS One
https://www.readbyqxmd.com/read/26856418/redifferentiation-of-expanded-human-islet-%C3%AE-cells-by-inhibition-of-arx
#2
Orr Friedman-Mazursky, Ran Elkon, Shimon Efrat
Ex-vivo expansion of adult human islet β cells has been evaluated for generation of abundant insulin-producing cells for transplantation; however, lineage-tracing has demonstrated that this process results in β-cell dedifferentiation. Redifferentiation of β-cell-derived (BCD) cells can be achieved using a combination of soluble factors termed Redifferentiation Cocktail (RC); however, this treatment leads to redifferentiation of only a fraction of BCD cells. This study aimed at improving redifferentiation efficiency by affecting the balance of islet progenitor-cell transcription factors activated by RC treatment...
2016: Scientific Reports
https://www.readbyqxmd.com/read/26633894/the-role-of-arx-in-human-pancreatic-endocrine-specification
#3
Blair K Gage, Ali Asadi, Robert K Baker, Travis D Webber, Rennian Wang, Masayuki Itoh, Masaharu Hayashi, Rie Miyata, Takumi Akashi, Timothy J Kieffer
The in vitro differentiation of human embryonic stem cells (hESCs) offers a model system to explore human development. Humans with mutations in the transcription factor Aristaless Related Homeobox (ARX) often suffer from the syndrome X-linked lissencephaly with ambiguous genitalia (XLAG), affecting many cell types including those of the pancreas. Indeed, XLAG pancreatic islets lack glucagon and pancreatic polypeptide-positive cells but retain somatostatin, insulin, and ghrelin-positive cells. To further examine the role of ARX in human pancreatic endocrine development, we utilized genomic editing in hESCs to generate deletions in ARX...
2015: PloS One
https://www.readbyqxmd.com/read/26319183/pax4-acts-as-a-key-player-in-pancreas-development-and-plasticity
#4
REVIEW
Tiziana Napolitano, Fabio Avolio, Monica Courtney, Andhira Vieira, Noémie Druelle, Nouha Ben-Othman, Biljana Hadzic, Sergi Navarro, Patrick Collombat
The embryonic development of the pancreas is orchestrated by a complex and coordinated transcription factor network. Neurogenin3 (Neurog3) initiates the endocrine program by activating the expression of additional transcription factors driving survival, proliferation, maturation and lineage allocation of endocrine precursors. Among the direct targets of Neurog3, Pax4 appears as one of the key regulators of β-cell specification. Indeed, mice lacking Pax4 die a few days postpartum, as they develop severe hyperglycemia due to the absence of mature pancreatic β-cells...
August 2015: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/26123382/everolimus-and-pancreatic-neuroendocrine-tumors-pnets-activity-resistance-and-how-to-overcome-it
#5
REVIEW
Monica Capozzi, Ieranò Caterina, Chiara De Divitiis, Claudia von Arx, Piera Maiolino, Fabiana Tatangelo, Ernesta Cavalcanti, Elena Di Girolamo, Rosario Vincenzo Iaffaioli, Stefania Scala, Salvatore Tafuto
Neuroendocrine tumors (NET) are rare malignancies, with the most common site of origin being from the gastrointestinal tract, particularly the pancreas, small bowel and appendix. Pancreatic neuroendocrine tumors (PNETs) can be functional, hormone secreting tumors, and can have distinctive symptoms leading to the diagnosis. In contrast nonfunctional tumors, the majority of PNETs, usually present later either incidentally or due to tumor bulk symptoms. Currently Everolimus, an inhibitor of mammalian target of rapamycin (mTOR), is the most promising drug for patients with unresectable, metastatic disease, in progressive well-differentiated PNETs and many studies are ongoing to demonstrate its effects on the other neuroendocrine histotipes...
September 2015: International Journal of Surgery
https://www.readbyqxmd.com/read/25931474/altered-phenotype-of-%C3%AE-cells-and-other-pancreatic-cell-lineages-in-patients-with-diffuse-congenital-hyperinsulinism-in-infancy-caused-by-mutations-in-the-atp-sensitive-k-channel
#6
Rachel J Salisbury, Bing Han, Rachel E Jennings, Andrew A Berry, Adam Stevens, Zainab Mohamed, Sarah A Sugden, Ronald De Krijger, Sarah E Cross, Paul P V Johnson, Melanie Newbould, Karen E Cosgrove, Karen Piper Hanley, Indraneel Banerjee, Mark J Dunne, Neil A Hanley
Diffuse congenital hyperinsulinism in infancy (CHI-D) arises from mutations inactivating the KATP channel; however, the phenotype is difficult to explain from electrophysiology alone. Here we studied wider abnormalities in the β-cell and other pancreatic lineages. Islets were disorganized in CHI-D compared with controls. PAX4 and ARX expression was decreased. A tendency toward increased NKX2.2 expression was consistent with its detection in two-thirds of CHI-D δ-cell nuclei, similar to the fetal pancreas, and implied immature δ-cell function...
September 2015: Diabetes
https://www.readbyqxmd.com/read/25918232/tshz1-regulates-pancreatic-%C3%AE-cell-maturation
#7
Jeffrey C Raum, Scott A Soleimanpour, David N Groff, Nathalie Coré, Laurent Fasano, Alistair N Garratt, Chunhua Dai, Alvin C Powers, Doris A Stoffers
The homeodomain transcription factor Pdx1 controls pancreas organogenesis, specification of endocrine pancreas progenitors, and the postnatal growth and function of pancreatic β-cells. Pdx1 expression in human-derived stem cells is used as a marker for induced pancreatic precursor cells. Unfortunately, the differentiation efficiency of human pancreatic progenitors into functional β-cells is poor. In order to gain insight into the genes that Pdx1 regulates during differentiation, we performed Pdx1 chromatin immunoprecipitation followed by high-throughput sequencing of embryonic day (e) 13...
August 2015: Diabetes
https://www.readbyqxmd.com/read/24876585/personalized-state-space-modeling-of-glucose-dynamics-for-type-1-diabetes-using-continuously-monitored-glucose-insulin-dose-and-meal-intake-an-extended-kalman-filter-approach
#8
Qian Wang, Peter Molenaar, Saurabh Harsh, Kenneth Freeman, Jinyu Xie, Carol Gold, Mike Rovine, Jan Ulbrecht
An essential component of any artificial pancreas is on the prediction of blood glucose levels as a function of exogenous and endogenous perturbations such as insulin dose, meal intake, and physical activity and emotional tone under natural living conditions. In this article, we present a new data-driven state-space dynamic model with time-varying coefficients that are used to explicitly quantify the time-varying patient-specific effects of insulin dose and meal intake on blood glucose fluctuations. Using the 3-variate time series of glucose level, insulin dose, and meal intake of an individual type 1 diabetic subject, we apply an extended Kalman filter (EKF) to estimate time-varying coefficients of the patient-specific state-space model...
March 2014: Journal of Diabetes Science and Technology
https://www.readbyqxmd.com/read/24487024/grg3-tle3-and-grg1-tle1-induce-monohormonal-pancreatic-%C3%AE-cells-while-repressing-%C3%AE-cell-functions
#9
David E Metzger, Chengyang Liu, Amin Sam Ziaie, Ali Naji, Kenneth S Zaret
In the pancreas, α- and β-cells possess a degree of plasticity. In vitro differentiation of pluripotent cells yields mostly α- and polyhormonal β-like cells, indicating a gap in understanding of how functional monohormonal β-cells are formed and of the endogenous repressive mechanisms used to maintain β-cell identity. We show that the corepressor Grg3 is expressed in almost all β-cells throughout embryogenesis to adulthood. However, Grg3 is expressed in fewer nascent α-cells and is progressively lost from α-cells as endocrine cells mature into adulthood...
May 2014: Diabetes
https://www.readbyqxmd.com/read/24307230/arx-arx-is-expressed-in-germ-cells-during-spermatogenesis-in-both-marsupial-and-mouse
#10
Hongshi Yu, Andrew J Pask, Yanqiu Hu, Geoff Shaw, Marilyn B Renfree
The X-linked aristaless gene, ARX, is essential for the development of the gonads, forebrain, olfactory bulb, pancreas, and skeletal muscle in mice and humans. Mutations cause neurological diseases, often accompanied by ambiguous genitalia. There are a disproportionately high number of testis and brain genes on the human and mouse X chromosomes. It is still unknown whether the X chromosome accrued these genes during its evolution or whether genes that find themselves on the X chromosome evolve such roles. ARX was originally autosomal in mammals and remains so in marsupials, whereas in eutherian mammals it translocated to the X chromosome...
March 2014: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/24236044/arx-polyalanine-expansion-in-mice-leads-to-reduced-pancreatic-%C3%AE-cell-specification-and-increased-%C3%AE-cell-death
#11
Crystal L Wilcox, Natalie A Terry, Catherine Lee May
ARX/Arx is a homeodomain-containing transcription factor necessary for the specification and early maintenance of pancreatic endocrine α-cells. Many transcription factors important to pancreas development, including ARX/Arx, are also crucial for proper brain development. Although null mutations of ARX in human patients result in the severe neurologic syndrome XLAG (X-linked lissencephaly associated with abnormal genitalia), the most common mutation is the expansion of the first polyalanine tract of ARX, which results primarily in the clinical syndrome ISSX (infantile spasms)...
2013: PloS One
https://www.readbyqxmd.com/read/24122442/reduced-polyalanine-expanded-arx-mutant-protein-in-developing-mouse-subpallium-alters-lmo1-transcriptional-regulation
#12
Kristie Lee, Tessa Mattiske, Kunio Kitamura, Jozef Gecz, Cheryl Shoubridge
Intellectual disability (ID) is a highly prevalent disorder that affects 1-3% of the population. The Aristaless-related homeobox gene (ARX) is a frequently mutated X-linked ID gene and encodes a transcription factor indispensable for proper forebrain, testis and pancreas development. Polyalanine expansions account for over half of all mutations in ARX and clinically give rise to a spectrum of ID and seizures. To understand how the polyalanine expansions cause the clinical phenotype, we studied mouse models of the two most frequent polyalanine expansion mutations (Arx((GCG)7) and Arx(432-455dup24))...
February 15, 2014: Human Molecular Genetics
https://www.readbyqxmd.com/read/23940571/gastrin-a-distinct-fate-of-neurogenin3-positive-progenitor-cells-in-the-embryonic-pancreas
#13
Yaron Suissa, Judith Magenheim, Miri Stolovich-Rain, Ayat Hija, Patrick Collombat, Ahmed Mansouri, Lori Sussel, Beatriz Sosa-Pineda, Kyle McCracken, James M Wells, R Scott Heller, Yuval Dor, Benjamin Glaser
Neurogenin3(+) (Ngn3(+)) progenitor cells in the developing pancreas give rise to five endocrine cell types secreting insulin, glucagon, somatostatin, pancreatic polypeptide and ghrelin. Gastrin is a hormone produced primarily by G-cells in the stomach, where it functions to stimulate acid secretion by gastric parietal cells. Gastrin is expressed in the embryonic pancreas and is common in islet cell tumors, but the lineage and regulators of pancreatic gastrin(+) cells are not known. We report that gastrin is abundantly expressed in the embryonic pancreas and disappears soon after birth...
2013: PloS One
https://www.readbyqxmd.com/read/23852729/reconstituting-pancreas-development-from-purified-progenitor-cells-reveals-genes-essential-for-islet-differentiation
#14
Takuya Sugiyama, Cecil M Benitez, Amar Ghodasara, Lucy Liu, Graeme W McLean, Jonghyeob Lee, Timothy A Blauwkamp, Roeland Nusse, Christopher V E Wright, Guoqiang Gu, Seung K Kim
Developmental biology is challenged to reveal the function of numerous candidate genes implicated by recent genome-scale studies as regulators of organ development and diseases. Recapitulating organogenesis from purified progenitor cells that can be genetically manipulated would provide powerful opportunities to dissect such gene functions. Here we describe systems for reconstructing pancreas development, including islet β-cell and α-cell differentiation, from single fetal progenitor cells. A strict requirement for native genetic regulators of in vivo pancreas development, such as Ngn3, Arx, and Pax4, revealed the authenticity of differentiation programs in vitro...
July 30, 2013: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/23785486/pancreatic-%C3%AE-cell-specific-deletion-of-mouse-arx-leads-to-%C3%AE-cell-identity-loss
#15
Crystal L Wilcox, Natalie A Terry, Erik R Walp, Randall A Lee, Catherine Lee May
The specification and differentiation of pancreatic endocrine cell populations (α-, β-, δ, PP- and ε-cells) is orchestrated by a combination of transcriptional regulators. In the pancreas, Aristaless-related homeobox gene (Arx) is expressed first in the endocrine progenitors and then restricted to glucagon-producing α-cells. While the functional requirement of Arx in early α-cell specification has been investigated, its role in maintaining α-cell identity has yet to be explored. To study this later role of Arx, we have generated mice in which the Arx gene has been ablated specifically in glucagon-producing α-cells...
2013: PloS One
https://www.readbyqxmd.com/read/23671715/aristaless-related-homeobox-plays-a-key-role-in-hyperplasia-of-the-pancreas-islet-%C3%AE-like-cells-in-mice-deficient-in-proglucagon-derived-peptides
#16
Sai Xu, Yoshitaka Hayashi, Yoshiko Takagishi, Mariko Itoh, Yoshiharu Murata
Defects in glucagon action can cause hyperplasia of islet α-cells, however, the underlying mechanisms remain largely to be elucidated. Mice homozygous for a glucagon-GFP knock-in allele (Gcg(gfp/gfp) ) completely lack proglucagon-derived peptides and exhibit hyperplasia of GFP-positive α-like cells. Expression of the transcription factor, aristaless-related homeobox (ARX), is also increased in the Gcg(gfp/gfp) pancreas. Here, we sought to elucidate the role of ARX in the hyperplasia of α-like cells through analyses of two Arx mutant alleles (Arx(P355L/Y) and Arx ([330insGCG]7/Y) ) that have different levels of impairment of their function...
2013: PloS One
https://www.readbyqxmd.com/read/23382704/nkx6-1-controls-a-gene-regulatory-network-required-for-establishing-and-maintaining-pancreatic-beta-cell-identity
#17
Ashleigh E Schaffer, Brandon L Taylor, Jacqueline R Benthuysen, Jingxuan Liu, Fabrizio Thorel, Weiping Yuan, Yang Jiao, Klaus H Kaestner, Pedro L Herrera, Mark A Magnuson, Catherine Lee May, Maike Sander
All pancreatic endocrine cell types arise from a common endocrine precursor cell population, yet the molecular mechanisms that establish and maintain the unique gene expression programs of each endocrine cell lineage have remained largely elusive. Such knowledge would improve our ability to correctly program or reprogram cells to adopt specific endocrine fates. Here, we show that the transcription factor Nkx6.1 is both necessary and sufficient to specify insulin-producing beta cells. Heritable expression of Nkx6...
2013: PLoS Genetics
https://www.readbyqxmd.com/read/23244389/pax4-is-not-essential-for-beta-cell-differentiation-in-zebrafish-embryos-but-modulates-alpha-cell-generation-by-repressing-arx-gene-expression
#18
Joachim Djiotsa, Vincianne Verbruggen, Jean Giacomotto, Minaka Ishibashi, Elisabeth Manning, Silke Rinkwitz, Isabelle Manfroid, Marianne L Voz, Bernard Peers
BACKGROUND: Genetic studies in mouse have demonstrated the crucial function of PAX4 in pancreatic cell differentiation. This transcription factor specifies β- and δ-cell fate at the expense of α-cell identity by repressing Arx gene expression and ectopic expression of PAX4 in α-cells is sufficient to convert them into β-cells. Surprisingly, no Pax4 orthologous gene can be found in chicken and Xenopus tropicalis raising the question of the function of pax4 gene in lower vertebrates such as in fish...
2012: BMC Developmental Biology
https://www.readbyqxmd.com/read/23193182/islet-%C3%AE-%C3%AE-and-%C3%AE-cell-development-is-controlled-by-the-ldb1-coregulator-acting-primarily-with-the-islet-1-transcription-factor
#19
Chad S Hunter, Shilpy Dixit, Tsadok Cohen, Benjamin Ediger, Crystal Wilcox, Mark Ferreira, Heiner Westphal, Roland Stein, Catherine Lee May
Ldb1 and Ldb2 are coregulators that mediate Lin11-Isl1-Mec3 (LIM)-homeodomain (HD) and LIM-only transcription factor-driven gene regulation. Although both Ldb1 and Ldb2 mRNA were produced in the developing and adult pancreas, immunohistochemical analysis illustrated a broad Ldb1 protein expression pattern during early pancreatogenesis, which subsequently became enriched in islet and ductal cells perinatally. The islet-enriched pattern of Ldb1 was similar to pan-endocrine cell-expressed Islet-1 (Isl1), which was demonstrated in this study to be the primary LIM-HD transcription factor in developing and adult islet cells...
March 2013: Diabetes
https://www.readbyqxmd.com/read/22847495/%C3%AE-cell-role-in-%C3%AE-cell-generation-and-regeneration
#20
REVIEW
Joel F Habener, Violeta Stanojevic
This review considers the role of α-cells in β-cell generation and regeneration. We present recent evidence obtained from lineage-tracing studies showing that α-cells can serve as progenitors of β-cells and present a hypothetical model how injured β-cells might activate α-cells in adult islets to promote β-cell regeneration. β-cells appear to arise by way of their trans-differentiation from undifferentiated α progenitor cells, pro-α-cells, both during embryonic development of the islets and in the adult pancreas in response to β-cell injuries...
May 2012: Islets
keyword
keyword
72294
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"