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noah shroyer

Anubama Rajan, Lucy Vela, Xi-Lei Zeng, Xiaomin Yu, Noah Shroyer, Sarah E Blutt, Nina M Poole, Lily G Carlin, James P Nataro, Mary K Estes, Pablo C Okhuysen, Anthony W Maresso
Enteroaggregative Escherichia coli (EAEC) is an important diarrheal pathogen and a cause of both acute and chronic diarrhea. It is a common cause of pediatric bacterial diarrhea in developing countries. Despite its discovery in 1987, the intestinal tropism of the pathogen remains unknown. Cell lines used to study EAEC adherence include the HEp-2, T-84, and Caco-2 lines, but they exhibit abnormal metabolism and large variations in gene expression. Animal models either do not faithfully manifest human clinical symptoms or are cumbersome and expensive...
February 20, 2018: MBio
Winnie Y Zou, Sarah E Blutt, Xi-Lei Zeng, Min-Shan Chen, Yuan-Hung Lo, David Castillo-Azofeifa, Ophir D Klein, Noah F Shroyer, Mark Donowitz, Mary K Estes
Intestinal stem cells (ISCs) maintain and repair the intestinal epithelium. While regeneration after ISC-targeted damage is increasingly understood, injury-repair mechanisms that direct regeneration following injuries to differentiated cells remain uncharacterized. The enteric pathogen, rotavirus, infects and damages differentiated cells while sparing all ISC populations, thus allowing the unique examination of the response of intact ISC compartments during injury-repair. Upon rotavirus infection in mice, ISC compartments robustly expand and proliferating cells rapidly migrate...
January 23, 2018: Cell Reports
Jorge O Múnera, Nambirajan Sundaram, Scott A Rankin, David Hill, Carey Watson, Maxime Mahe, Jefferson E Vallance, Noah F Shroyer, Katie L Sinagoga, Adrian Zarzoso-Lacoste, Jonathan R Hudson, Jonathan C Howell, Praneet Chatuvedi, Jason R Spence, John M Shannon, Aaron M Zorn, Michael A Helmrath, James M Wells
Gastric and small intestinal organoids differentiated from human pluripotent stem cells (hPSCs) have revolutionized the study of gastrointestinal development and disease. Distal gut tissues such as cecum and colon, however, have proved considerably more challenging to derive in vitro. Here we report the differentiation of human colonic organoids (HCOs) from hPSCs. We found that BMP signaling is required to establish a posterior SATB2+ domain in developing and postnatal intestinal epithelium. Brief activation of BMP signaling is sufficient to activate a posterior HOX code and direct hPSC-derived gut tube cultures into HCOs...
July 6, 2017: Cell Stem Cell
Yuan-Hung Lo, Taeko K Noah, Min-Shan Chen, Winnie Zou, Ester Borras, Eduardo Vilar, Noah F Shroyer
BACKGROUND & AIMS: The canonical Wnt signaling pathway activates the transcriptional activity of β-catenin. This pathway is often activated in colorectal cancer cells, but strategies to block it in tumors have not been effective. The SAM pointed domain containing ETS transcription factor (SPDEF) suppresses formation of colon tumors by unclear mechanisms. We investigated these mechanisms and the effects of SPDEF on β-catenin activity in mouse models of colorectal cancer (CRC), CRC cell lines, and mouse and human normal and cancer colonoids...
July 2017: Gastroenterology
Kristina N-M Daeffler, Jeffrey D Galley, Ravi U Sheth, Laura C Ortiz-Velez, Christopher O Bibb, Noah F Shroyer, Robert A Britton, Jeffrey J Tabor
There is a groundswell of interest in using genetically engineered sensor bacteria to study gut microbiota pathways, and diagnose or treat associated diseases. Here, we computationally identify the first biological thiosulfate sensor and an improved tetrathionate sensor, both two-component systems from marine Shewanella species, and validate them in laboratory Escherichia coli Then, we port these sensors into a gut-adapted probiotic E. coli strain, and develop a method based upon oral gavage and flow cytometry of colon and fecal samples to demonstrate that colon inflammation (colitis) activates the thiosulfate sensor in mice harboring native gut microbiota...
April 3, 2017: Molecular Systems Biology
Dana Almohazey, Yuan-Hung Lo, Claire V Vossler, Alan J Simmons, Jonathan J Hsieh, Edie B Bucar, Michael A Schumacher, Kathryn E Hamilton, Ken S Lau, Noah F Shroyer, Mark R Frey
Paneth cells (PCs), a secretory population located at the base of the intestinal crypt, support the intestinal stem cells (ISC) with growth factors and participate in innate immunity by releasing antimicrobial peptides, including lysozyme and defensins. PC dysfunction is associated with disorders such as Crohn's disease and necrotizing enterocolitis, but the specific pathways regulating PC development and function are not fully understood. Here we tested the role of the neuregulin receptor ErbB3 in control of PC differentiation and the ISC niche...
May 2017: Cell Death and Differentiation
Yuan-Hung Lo, Eunah Chung, Zhaohui Li, Ying-Wooi Wan, Maxime M Mahe, Min-Shan Chen, Taeko K Noah, Kristin N Bell, Hari Krishna Yalamanchili, Tiemo J Klisch, Zhandong Liu, Joo-Seop Park, Noah F Shroyer
BACKGROUND & AIMS: The transcription factor atonal homolog 1 (ATOH1) controls the fate of intestinal progenitors downstream of the Notch signaling pathway. Intestinal progenitors that escape Notch activation express high levels of ATOH1 and commit to a secretory lineage fate, implicating ATOH1 as a gatekeeper for differentiation of intestinal epithelial cells. Although some transcription factors downstream of ATOH1, such as SPDEF, have been identified to specify differentiation and maturation of specific cell types, the bona fide transcriptional targets of ATOH1 still largely are unknown...
January 2017: Cellular and Molecular Gastroenterology and Hepatology
Javeed Jattan, Cayla Rodia, Diana Li, Adama Diakhate, Hongli Dong, Amy Bataille, Noah F Shroyer, Alison B Kohan
Since its initial report in 2009, the intestinal enteroid culture system has been a powerful tool used to study stem cell biology and development in the gastrointestinal tract. However, a major question is whether enteroids retain intestinal function and physiology. There have been significant contributions describing ion transport physiology of human intestinal organoid cultures, as well as physiology of gastric organoids, but critical studies on dietary fat absorption and chylomicron synthesis in primary intestinal enteroids have not been undertaken...
May 2017: Journal of Lipid Research
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 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...
March 6, 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
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