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noah shroyer

Noah F Shroyer
Organoid technologies have significant potential as effective patient avatars. Fujii et al. (2016) and van de Wetering et al. (2015) derive biobanks of colorectal tumor and matching normal organoids and identify associations between tumor subtype, oncogenic drivers, gene-drug interactions, and varying niche requirements for tumor organoid growth, engraftment, and metastasis.
June 2, 2016: Cell Stem Cell
Caroline A Lindemans, Marco Calafiore, Anna M Mertelsmann, Margaret H O'Connor, Jarrod A Dudakov, Robert R Jenq, Enrico Velardi, Lauren F Young, Odette M Smith, Gillian Lawrence, Juliet A Ivanov, Ya-Yuan Fu, Shuichiro Takashima, Guoqiang Hua, Maria L Martin, Kevin P O'Rourke, Yuan-Hung Lo, Michal Mokry, Monica Romera-Hernandez, Tom Cupedo, Lukas E Dow, Edward E Nieuwenhuis, Noah F Shroyer, Chen Liu, Richard Kolesnick, Marcel R M van den Brink, Alan M Hanash
Epithelial regeneration is critical for barrier maintenance and organ function after intestinal injury. The intestinal stem cell (ISC) niche provides Wnt, Notch and epidermal growth factor (EGF) signals supporting Lgr5(+) crypt base columnar ISCs for normal epithelial maintenance. However, little is known about the regulation of the ISC compartment after tissue damage. Using ex vivo organoid cultures, here we show that innate lymphoid cells (ILCs), potent producers of interleukin-22 (IL-22) after intestinal injury, increase the growth of mouse small intestine organoids in an IL-22-dependent fashion...
December 24, 2015: Nature
Eitaro Aihara, Maxime M Mahe, Michael A Schumacher, Andrea L Matthis, Rui Feng, Wenwen Ren, Taeko K Noah, Toru Matsu-ura, Sean R Moore, Christian I Hong, Yana Zavros, Scott Herness, Noah F Shroyer, Ken Iwatsuki, Peihua Jiang, Michael A Helmrath, Marshall H Montrose
Leucine-rich repeat-containing G-protein coupled receptor 5-expressing (Lgr5(+)) cells have been identified as stem/progenitor cells in the circumvallate papillae, and single cultured Lgr5(+) cells give rise to taste cells. Here we use circumvallate papilla tissue to establish a three-dimensional culture system (taste bud organoids) that develops phenotypic characteristics similar to native tissue, including a multilayered epithelium containing stem/progenitor in the outer layers and taste cells in the inner layers...
2015: Scientific Reports
Caitlyn W Barrett, Vishruth K Reddy, Sarah P Short, Amy K Motley, Mary K Lintel, Amber M Bradley, Tanner Freeman, Jefferson Vallance, Wei Ning, Bobak Parang, Shenika V Poindexter, Barbara Fingleton, Xi Chen, Mary K Washington, Keith T Wilson, Noah F Shroyer, Kristina E Hill, Raymond F Burk, Christopher S Williams
Patients with inflammatory bowel disease are at increased risk for colon cancer due to augmented oxidative stress. These patients also have compromised antioxidant defenses as the result of nutritional deficiencies. The micronutrient selenium is essential for selenoprotein production and is transported from the liver to target tissues via selenoprotein P (SEPP1). Target tissues also produce SEPP1, which is thought to possess an endogenous antioxidant function. Here, we have shown that mice with Sepp1 haploinsufficiency or mutations that disrupt either the selenium transport or the enzymatic domain of SEPP1 exhibit increased colitis-associated carcinogenesis as the result of increased genomic instability and promotion of a protumorigenic microenvironment...
July 1, 2015: Journal of Clinical Investigation
Stacy R Finkbeiner, David R Hill, Christopher H Altheim, Priya H Dedhia, Matthew J Taylor, Yu-Hwai Tsai, Alana M Chin, Maxime M Mahe, Carey L Watson, Jennifer J Freeman, Roy Nattiv, Matthew Thomson, Ophir D Klein, Noah F Shroyer, Michael A Helmrath, Daniel H Teitelbaum, Peter J Dempsey, Jason R Spence
Human intestinal organoids (HIOs) are a tissue culture model in which small intestine-like tissue is generated from pluripotent stem cells. By carrying out unsupervised hierarchical clustering of RNA-sequencing data, we demonstrate that HIOs most closely resemble human fetal intestine. We observed that genes involved in digestive tract development are enriched in both fetal intestine and HIOs compared to adult tissue, whereas genes related to digestive function and Paneth cell host defense are expressed at higher levels in adult intestine...
June 3, 2015: Stem Cell Reports
Rongli Zhang, Shila Gilbert, Xinsheng Yao, Jefferson Vallance, Kris Steinbrecher, Richard Moriggl, Dongsheng Zhang, Madhu Eluri, Haifeng Chen, Huiqing Cao, Noah Shroyer, Lee Denson, Xiaonan Han
Dioscoreaceae, a kind of yam plant, has been recommended for treatment of chronic inflammatory conditions. However, the mechanisms are poorly defined. Methyl protodioscin (MPD) is one of the main bioactive components in Dioscoreaceae. Here, we aim to determine the mechanisms by which MPD ameliorates intestinal inflammation. Surgical intestinal specimens were collected from inflammatory bowel diseases (IBD) patients to perform organ culture. Experimental colitis was induced in mice by dextran sulfate sodium (DSS) or Citrobacter rodentium, and was then treated with MPD...
March 2015: Pharmacology Research & Perspectives
Margaret A Goodell, Hoang Nguyen, Noah Shroyer
Somatic stem cells replenish many tissues throughout life to repair damage and to maintain tissue homeostasis. Stem cell function is frequently described as following a hierarchical model in which a single master cell undergoes self-renewal and differentiation into multiple cell types and is responsible for most regenerative activity. However, recent data from studies on blood, skin and intestinal epithelium all point to the concomitant action of multiple types of stem cells with distinct everyday roles. Under stress conditions such as acute injury, the surprising developmental flexibility of these stem cells enables them to adapt to diverse roles and to acquire different regeneration capabilities...
May 2015: Nature Reviews. Molecular Cell Biology
Maxime M Mahe, Nambirajan Sundaram, Carey L Watson, Noah F Shroyer, Michael A Helmrath
The epithelium of the gastrointestinal tract is constantly renewed as it turns over. This process is triggered by the proliferation of intestinal stem cells (ISCs) and progeny that progressively migrate and differentiate toward the tip of the villi. These processes, essential for gastrointestinal homeostasis, have been extensively studied using multiple approaches. Ex vivo technologies, especially primary cell cultures have proven to be promising for understanding intestinal epithelial functions. A long-term primary culture system for mouse intestinal crypts has been established to generate 3-dimensional epithelial organoids...
2015: Journal of Visualized Experiments: JoVE
Sean R Moore, Marjorie M Guedes, Tie B Costa, Jefferson Vallance, Elizabeth A Maier, Kristina J Betz, Eitaro Aihara, Maxime M Mahe, Aldo A M Lima, Reinaldo B Oriá, Noah F Shroyer
L-glutamine (Gln) is a key metabolic fuel for intestinal epithelial cell proliferation and survival and may be conditionally essential for gut homeostasis during catabolic states. We show that L-alanyl-L-glutamine (Ala-Gln), a stable Gln dipeptide, protects mice against jejunal crypt depletion in the setting of dietary protein and fat deficiency. Separately, we show that murine crypt cultures (enteroids) derived from the jejunum require Gln or Ala-Gln for maximal expansion. Once expanded, enteroids deprived of Gln display a gradual atrophy of cryptlike domains, with decreased epithelial proliferation, but stable proportions of Paneth and goblet cell differentiation, at 24 h...
May 15, 2015: American Journal of Physiology. Gastrointestinal and Liver Physiology
Michael A Schumacher, Eitaro Aihara, Rui Feng, Amy Engevik, Noah F Shroyer, Karen M Ottemann, Roger T Worrell, Marshall H Montrose, Ramesh A Shivdasani, Yana Zavros
KEY POINTS: An in vitro approach to study gastric development is primary mouse-derived epithelium cultured as three-dimensional spheroids known as organoids. We have devised two unique gastric fundic-derived organoid cultures: model 1 for the expansion of gastric fundic stem cells, and model 2 for the maintenance of mature cell lineages. Organoids maintained in co-culture with immortalized stomach mesenchymal cells express robust numbers of surface pit, mucous neck, chief, endocrine and parietal cells...
April 15, 2015: Journal of Physiology
Shila Gilbert, Harini Nivarthi, Christopher N Mayhew, Yuan-Hung Lo, Taeko K Noah, Jefferson Vallance, Thomas Rülicke, Mathias Müller, Anil G Jegga, Wenjuan Tang, Dongsheng Zhang, Michael Helmrath, Noah Shroyer, Richard Moriggl, Xiaonan Han
Intestinal epithelial stem cells (IESCs) control the intestinal homeostatic response to inflammation and regeneration. The underlying mechanisms are unclear. Cytokine-STAT5 signaling regulates intestinal epithelial homeostasis and responses to injury. We link STAT5 signaling to IESC replenishment upon injury by depletion or activation of Stat5 transcription factor. We found that depletion of Stat5 led to deregulation of IESC marker expression and decreased LGR5(+) IESC proliferation. STAT5-deficient mice exhibited worse intestinal histology and impaired crypt regeneration after γ-irradiation...
February 10, 2015: Stem Cell Reports
Bobak Parang, Daniel Rosenblatt, Amanda D Williams, Mary K Washington, Frank Revetta, Sarah P Short, Vishruth K Reddy, Aubrey Hunt, Noah F Shroyer, Michael E Engel, Scott W Hiebert, Christopher S Williams
Notch signaling largely determines intestinal epithelial cell fate. High Notch activity drives progenitors toward absorptive enterocytes by repressing secretory differentiation programs, whereas low Notch permits secretory cell assignment. Myeloid translocation gene-related 1 (MTGR1) is a transcriptional corepressor in the myeloid translocation gene/Eight-Twenty-One family. Given that Mtgr1(-/-) mice have a dramatic reduction of intestinal epithelial secretory cells, we hypothesized that MTGR1 is a key repressor of Notch signaling...
March 2015: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Lydia E Wroblewski, M Blanca Piazuelo, Rupesh Chaturvedi, Michael Schumacher, Eitaro Aihara, Rui Feng, Jennifer M Noto, Alberto Delgado, Dawn A Israel, Yana Zavros, Marshall H Montrose, Noah Shroyer, Pelayo Correa, Keith T Wilson, Richard M Peek
OBJECTIVE: Helicobacter pylori strains that express the oncoprotein CagA augment risk for gastric cancer. However, the precise mechanisms through which cag(+) strains heighten cancer risk have not been fully delineated and model systems that recapitulate the gastric niche are critical for understanding pathogenesis. Gastroids are three-dimensional organ-like structures that provide unique opportunities to study host-H. pylori interactions in a preclinical model. We used gastroids to inform and direct in vitro studies to define mechanisms through which H...
May 2015: Gut
Maxime M Mahe, Eitaro Aihara, Michael A Schumacher, Yana Zavros, Marshall H Montrose, Michael A Helmrath, Toshiro Sato, Noah F Shroyer
The intestinal epithelium constitutes a system of constant and rapid renewal triggered by proliferation of intestinal stem cells (ISCs), and is an ideal system for studying cell proliferation, migration, and differentiation. Primary cell cultures have proven to be promising for unraveling the mechanisms involved in epithelium homeostasis. In 2009, Sato et al. established a long-term primary culture to generate epithelial organoids (enteroids) with crypt- and villus-like epithelial domains representing the complete census of progenitors and differentiated cells...
2013: Current Protocols in Mouse Biology
Kristin N Bell, Noah F Shroyer
BACKGROUND: Krüpple-like factor 5 (KLF5) is a transcription factor that is highly expressed in the proliferative compartment of the intestinal crypt. There, it is thought to regulate epithelial turnover and homeostasis. AIM: In this study, we sought to determine the role for Klf5 in the maintenance of cellular proliferation, cytodifferentiation, and morphology of the crypt-villus axis. METHODS: Tamoxifen-induced recombination directed by the epithelial-specific Villin promoter (in Villin-CreERT2 transgenic mice) was used to delete Klf5 (in Klf5 (loxP/loxP) mice) from the adult mouse intestine and analyzed by immunostaining and RT-qPCR...
January 2015: Digestive Diseases and Sciences
Sean R Moore, Jill Pruszka, Jefferson Vallance, Eitaro Aihara, Toru Matsuura, Marshall H Montrose, Noah F Shroyer, Christian I Hong
Disruption of circadian rhythms is a risk factor for several human gastrointestinal (GI) diseases, ranging from diarrhea to ulcers to cancer. Four-dimensional tissue culture models that faithfully mimic the circadian clock of the GI epithelium would provide an invaluable tool to understand circadian regulation of GI health and disease. We hypothesized that rhythmicity of a key circadian component, PERIOD2 (PER2), would diminish along a continuum from ex vivo intestinal organoids (epithelial 'miniguts'), nontransformed mouse small intestinal epithelial (MSIE) cells and transformed human colorectal adenocarcinoma (Caco-2) cells...
September 2014: Disease Models & Mechanisms
Rui Feng, Eitaro Aihara, Susan Kenny, Li Yang, Jing Li, Andrea Varro, Marshall H Montrose, Noah F Shroyer, Timothy C Wang, Ramesh A Shivdasani, Yana Zavros
BACKGROUND & AIMS: Loss of expression of Sonic Hedgehog (Shh) from parietal cells results in hypergastrinemia in mice, accompanied by increased expression of Indian Hedgehog (Ihh) and hyperproliferation of surface mucous cells. We investigated whether hypergastrinemia induces gastric epithelial proliferation by activating Ihh signaling in mice. METHODS: We studied mice with parietal cell-specific deletion of Shh (PC-Shh(KO)) and hypergastrinemia, crossed with gastrin-deficient (GKO) mice (PC-Shh(KO)/GKO)...
September 2014: Gastroenterology
Megan K Fuller, Denver M Faulk, Nambirajan Sundaram, Maxime M Mahe, Kara M Stout, Richard J von Furstenberg, Brian J Smith, Kirk K McNaughton, Noah F Shroyer, Michael A Helmrath, Susan J Henning
Intestinal stem cells (ISCs) are responsible for renewal of the epithelium both during normal homeostasis and following injury. As such, they have significant therapeutic potential. However, whether ISCs can survive tissue storage is unknown. We hypothesize that, although the majority of epithelial cells might die, ISCs would remain viable for at least 24 h at 4 °C. To explore this hypothesis, jejuna of C57Bl6/J or Lgr5-LacZ mice were removed and either processed immediately or placed in phosphate-buffered saline at 4 °C...
November 2013: Cell and Tissue Research
Jaime Melendez, Ming Liu, Leesa Sampson, Shailaja Akunuru, Xiaonan Han, Jefferson Vallance, David Witte, Noah Shroyer, Yi Zheng
BACKGROUND & AIMS: Cdc42 is a Rho GTPase that regulates diverse cellular functions, including proliferation, differentiation, migration, and polarity. In the intestinal epithelium, a balance among these events maintains homeostasis. We used genetic techniques to investigate the role of Cdc42 in intestinal homeostasis and its mechanisms. METHODS: We disrupted Cdc42 specifically in intestinal epithelial cells by creating Cdc42flox/flox-villin-Cre+ and Cdc42flox/flox-Rosa26-CreER+ mice...
October 2013: Gastroenterology
Taeko K Noah, Yuan-Hung Lo, Allison Price, Gang Chen, Eileen King, Mary-Kay Washington, Bruce J Aronow, Noah F Shroyer
BACKGROUND & AIMS: Expression of the SAM pointed domain containing ETS transcription factor (SPDEF or prostate-derived ETS factor) is regulated by Atoh1 and is required for the differentiation of goblet and Paneth cells. SPDEF has been reported to suppress the development of breast, prostate, and colon tumors. We analyzed levels of SPDEF in colorectal tumor samples from patients and its tumor-suppressive functions in mouse models of colorectal cancer (CRC). METHODS: We analyzed levels of SPDEF messenger RNA and protein in more than 500 human CRC samples and more than 80 nontumor controls...
May 2013: Gastroenterology
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