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https://www.readbyqxmd.com/read/28448600/mscs-feeder-layers-induce-smg-self-organization-and-branching-morphogenesis
#1
Mahmoud Farahat, Gulsan Ara Sathi, Emilio Satoshi Hara, Hiroaki Taketa, Takuo Kuboki, Takuya Matsumoto
Dysfunction of salivary glands leads to several oral health problems, including dental caries, mastication and swallowing dysfunctions and multiple oral infections. Conventional treatments for such condition fell short of providing satisfying therapeutic results. Recent advances in organ regeneration therapy which utilize tissue stem cells to fabricate bioengineered 3D organ buds, have introduced a promising therapeutic tool for full functional organ regeneration. However, finding a sustainable and easily accessible cell source for such approaches is still challenging, especially in case of severely atrophied tissues such as irradiated salivary glands...
2017: PloS One
https://www.readbyqxmd.com/read/28448044/generation-of-ipsc-derived-human-brain-organoids-to-model-early-neurodevelopmental-disorders
#2
Elke Gabriel, Jay Gopalakrishnan
The restricted availability of suitable in vitro models that can reliably represent complex human brain development is a significant bottleneck that limits the translation of basic brain research into clinical application. While induced pluripotent stem cells (iPSCs) have replaced the ethically questionable human embryonic stem cells, iPSC-based neuronal differentiation studies remain descriptive at the cellular level but fail to adequately provide the details that could be derived from a complex, 3D human brain tissue...
April 14, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28442624/unphosphorylated-isgf3-drives-constitutive-expression-of-interferon-stimulated-genes-to-protect-against-viral-infections
#3
Wenshi Wang, Yuebang Yin, Lei Xu, Junhong Su, Fen Huang, Yijin Wang, Patrick P C Boor, Kan Chen, Wenhui Wang, Wanlu Cao, Xinying Zhou, Pengyu Liu, Luc J W van der Laan, Jaap Kwekkeboom, Maikel P Peppelenbosch, Qiuwei Pan
Interferon (IFN)-stimulated genes (ISGs) are antiviral effectors that are induced by IFNs through the formation of a tripartite transcription factor ISGF3, which is composed of IRF9 and phosphorylated forms of STAT1 and STAT2. However, we found that IFN-independent ISG expression was detectable in immortalized cell lines, primary intestinal and liver organoids, and liver tissues. The constitutive expression of ISGs was mediated by the unphosphorylated ISGF3 (U-ISGF3) complex, consisting of IRF9 together with unphosphorylated STAT1 and STAT2...
April 25, 2017: Science Signaling
https://www.readbyqxmd.com/read/28436965/a-three-dimensional-model-of-human-lung-development-and-disease-from-pluripotent-stem-cells
#4
Ya-Wen Chen, Sarah Xuelian Huang, Ana Luisa Rodrigues Toste de Carvalho, Siu-Hong Ho, Mohammad Naimul Islam, Stefano Volpi, Luigi D Notarangelo, Michael Ciancanelli, Jean-Laurent Casanova, Jahar Bhattacharya, Alice F Liang, Laura M Palermo, Matteo Porotto, Anne Moscona, Hans-Willem Snoeck
Recapitulation of lung development from human pluripotent stem cells (hPSCs) in three dimensions (3D) would allow deeper insight into human development, as well as the development of innovative strategies for disease modelling, drug discovery and regenerative medicine. We report here the generation from hPSCs of lung bud organoids (LBOs) that contain mesoderm and pulmonary endoderm and develop into branching airway and early alveolar structures after xenotransplantation and in Matrigel 3D culture. Expression analysis and structural features indicated that the branching structures reached the second trimester of human gestation...
May 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28346922/epigenetics-in-gastrointestinal-health-and-disease-spotlight-on-dna-methylation-in-the-intestinal-epithelium
#5
Matthias Zilbauer, Judith Kraiczy
Epigenetics can be defined as stable, potentially heritable changes in cellular phenotype caused by mechanisms other than alterations in the underlying DNA sequence. DNA methylation is amongst the most intensely studied epigenetic mechanisms and has been shown to play a major role in regulating fundamental aspects of cell biology including cellular differentiation, organ development, and cell type-specific gene expression. Importantly, it is becoming increasingly clear that epigenetic mechanisms operate at the interface between the genetic code and our environment and are able to mediate environmental changes into stable phenotypic alterations...
2017: Nestlé Nutrition Institute Workshop Series
https://www.readbyqxmd.com/read/28314593/25-hydroxycholesterol-protects-host-against-zika-virus-infection-and-its-associated-microcephaly-in-a-mouse-model
#6
Chunfeng Li, Yong-Qiang Deng, Shuo Wang, Feng Ma, Roghiyh Aliyari, Xing-Yao Huang, Na-Na Zhang, Momoko Watanabe, Hao-Long Dong, Ping Liu, Xiao-Feng Li, Qing Ye, Min Tian, Shuai Hong, Junwan Fan, Hui Zhao, Lili Li, Neda Vishlaghi, Jessie E Buth, Connie Au, Ying Liu, Ning Lu, Peishuang Du, F Xiao-Feng Qin, Bo Zhang, Danyang Gong, Xinghong Dai, Ren Sun, Bennett G Novitch, Zhiheng Xu, Cheng-Feng Qin, Genhong Cheng
Zika virus (ZIKV) has become a public health threat due to its global transmission and link to severe congenital disorders. The host immune responses to ZIKV infection have not been fully elucidated, and effective therapeutics are not currently available. Herein, we demonstrated that cholesterol-25-hydroxylase (CH25H) was induced in response to ZIKV infection and that its enzymatic product, 25-hydroxycholesterol (25HC), was a critical mediator of host protection against ZIKV. Synthetic 25HC addition inhibited ZIKV infection in vitro by blocking viral entry, and treatment with 25HC reduced viremia and conferred protection against ZIKV in mice and rhesus macaques...
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28151409/helicobacter-pylori-induced-gastric-pathology-insights-from-in-vivo-and-ex-vivo-models
#7
REVIEW
Michael D Burkitt, Carrie A Duckworth, Jonathan M Williams, D Mark Pritchard
Gastric colonization with Helicobacter pylori induces diverse human pathological conditions, including superficial gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma and its precursors. The treatment of these conditions often relies on the eradication of H. pylori, an intervention that is increasingly difficult to achieve and that does not prevent disease progression in some contexts. There is, therefore, a pressing need to develop new experimental models of H...
February 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28132835/recent-zika-virus-isolates-induce-premature-differentiation-of-neural-progenitors-in-human-brain-organoids
#8
Elke Gabriel, Anand Ramani, Ulrike Karow, Marco Gottardo, Karthick Natarajan, Li Ming Gooi, Gladiola Goranci-Buzhala, Oleg Krut, Franziska Peters, Milos Nikolic, Suvi Kuivanen, Essi Korhonen, Teemu Smura, Olli Vapalahti, Argyris Papantonis, Jonas Schmidt-Chanasit, Maria Riparbelli, Giuliano Callaini, Martin Krönke, Olaf Utermöhlen, Jay Gopalakrishnan
The recent Zika virus (ZIKV) epidemic is associated with microcephaly in newborns. Although the connection between ZIKV and neurodevelopmental defects is widely recognized, the underlying mechanisms are poorly understood. Here we show that two recently isolated strains of ZIKV, an American strain from an infected fetal brain (FB-GWUH-2016) and a closely-related Asian strain (H/PF/2013), productively infect human iPSC-derived brain organoids. Both of these strains readily target to and replicate in proliferating ventricular zone (VZ) apical progenitors...
March 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28124153/gastric-organoids-an-emerging-model-system-to-study-helicobacter-pylori-pathogenesis
#9
Malvika Pompaiah, Sina Bartfeld
Helicobacter research classically uses fixed human tissue, animal models or cancer cell lines. Each of these study objects has its advantages and has brought central insights into the infection process. Nevertheless, in model systems for basic and medical research, there is a gap between two-dimensional and most often transformed cell cultures and three-dimensional, highly organized tissues. In recent years, stem cell research has provided the means to fill this gap. The identification of the niche factors that support growth, expansion and differentiation of stem cells in vitro has allowed the development of three-dimensional culture systems called organoids...
2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28041895/induction-of-expansion-and-folding-in-human-cerebral-organoids
#10
Yun Li, Julien Muffat, Attya Omer, Irene Bosch, Madeline A Lancaster, Mriganka Sur, Lee Gehrke, Juergen A Knoblich, Rudolf Jaenisch
An expansion of the cerebral neocortex is thought to be the foundation for the unique intellectual abilities of humans. It has been suggested that an increase in the proliferative potential of neural progenitors (NPs) underlies the expansion of the cortex and its convoluted appearance. Here we show that increasing NP proliferation induces expansion and folding in an in vitro model of human corticogenesis. Deletion of PTEN stimulates proliferation and generates significantly larger and substantially folded cerebral organoids...
March 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28005068/immuno-engineered-organoids-for-regulating-the-kinetics-of-b-cell-development-and-antibody-production
#11
Alberto Purwada, Ankur Singh
Induction of B-cell immunity against infection depends on the initiation of the germinal center (GC) reaction in secondary lymphoid organs. Ex vivo recapitulation of the GC reaction in 2D cultures results in transient cell growth, with poor yield and short-term survival. Furthermore, no reported 2D ex vivo system can modulate the kinetics of a GC-like phenotype or the rate of antibody class switching. This protocol describes a methodology for developing immune organoids that partially mimic the B-cell zone of a lymphoid tissue, for efficient and rapid generation of B cells with a GC-like phenotype from naive murine B cells...
January 2017: Nature Protocols
https://www.readbyqxmd.com/read/27990460/the-development-of-spasmolytic-polypeptide-tff2-expressing-metaplasia-spem-during-gastric-repair-is-absent-in-the-aged-stomach
#12
Amy C Engevik, Rui Feng, Eunyoung Choi, Shana White, Nina Bertaux-Skeirik, Jing Li, Maxime M Mahe, Eitaro Aihara, Li Yang, Betsy DiPasquale, Sunghee Oh, Kristen A Engevik, Andrew S Giraud, Marshall H Montrose, Mario Medvedovic, Michael A Helmrath, James R Goldenring, Yana Zavros
BACKGROUND & AIMS: During aging, physiological changes in the stomach result in more tenuous gastric tissue that is less capable of repairing injury, leading to increased susceptibility to chronic ulceration. Spasmolytic polypeptide/trefoil factor 2-expressing metaplasia (SPEM) is known to emerge after parietal cell loss and during Helicobacter pylori infection, however, its role in gastric ulcer repair is unknown. Therefore, we sought to investigate if SPEM plays a role in epithelial regeneration...
September 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/27912091/genetic-ablation-of-axl-does-not-protect-human-neural-progenitor-cells-and-cerebral-organoids-from-zika-virus-infection
#13
Michael F Wells, Max R Salick, Ole Wiskow, Daniel J Ho, Kathleen A Worringer, Robert J Ihry, Sravya Kommineni, Bilada Bilican, Joseph R Klim, Ellen J Hill, Liam T Kane, Chaoyang Ye, Ajamete Kaykas, Kevin Eggan
Zika virus (ZIKV) can cross the placental barrier, resulting in infection of the fetal brain and neurological defects including microcephaly. The cellular tropism of ZIKV and the identity of attachment factors used by the virus to gain access to key cell types involved in pathogenesis are under intense investigation. Initial studies suggested that ZIKV preferentially targets neural progenitor cells (NPCs), providing an explanation for the developmental phenotypes observed in some pregnancies. The AXL protein has been nominated as a key attachment factor for ZIKV in several cell types including NPCs...
December 1, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/27912090/advances-in-zika-virus-research-stem-cell-models-challenges-and-opportunities
#14
REVIEW
Guo-Li Ming, Hengli Tang, Hongjun Song
The re-emergence of Zika virus (ZIKV) and its suspected link with various disorders in newborns and adults led the World Health Organization to declare a global health emergency. In response, the stem cell field quickly established platforms for modeling ZIKV exposure using human pluripotent stem cell-derived neural progenitors and brain organoids, fetal tissues, and animal models. These efforts provided significant insight into cellular targets, pathogenesis, and underlying biological mechanisms of ZIKV infection as well as platforms for drug testing...
December 1, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/27680706/frizzled-proteins-are-colonic-epithelial-receptors-for-c-difficile-toxin-b
#15
Liang Tao, Jie Zhang, Paul Meraner, Alessio Tovaglieri, Xiaoqian Wu, Ralf Gerhard, Xinjun Zhang, William B Stallcup, Ji Miao, Xi He, Julian G Hurdle, David T Breault, Abraham L Brass, Min Dong
Clostridium difficile toxin B (TcdB) is a critical virulence factor that causes diseases associated with C. difficile infection. Here we carried out CRISPR-Cas9-mediated genome-wide screens and identified the members of the Wnt receptor frizzled family (FZDs) as TcdB receptors. TcdB binds to the conserved Wnt-binding site known as the cysteine-rich domain (CRD), with the highest affinity towards FZD1, 2 and 7. TcdB competes with Wnt for binding to FZDs, and its binding blocks Wnt signalling. FZD1/2/7 triple-knockout cells are highly resistant to TcdB, and recombinant FZD2-CRD prevented TcdB binding to the colonic epithelium...
October 20, 2016: Nature
https://www.readbyqxmd.com/read/27640087/modeling-infectious-diseases-and-host-microbe-interactions-in-gastrointestinal-organoids
#16
REVIEW
Sina Bartfeld
Advances in stem cell research have allowed the development of 3-dimensional (3D) primary cell cultures termed organoid cultures, as they closely mimic the in vivo organization of different cell lineages. Bridging the gap between 2-dimensional (2D) monotypic cancer cell lines and whole organisms, organoids are now widely applied to model development and disease. Organoids hold immense promise for addressing novel questions in host-microbe interactions, infectious diseases and the resulting inflammatory conditions...
December 15, 2016: Developmental Biology
https://www.readbyqxmd.com/read/27633294/mammalian-cell-cultures-as-models-for-mycobacterium-tuberculosis-human-immunodeficiency-virus-hiv-interaction-studies-a-review
#17
REVIEW
Walter Chingwaru, Richard H Glashoff, Jerneja Vidmar, Petrina Kapewangolo, Samantha L Sampson
Mycobacterium tuberculosis and human immunodeficiency virus (HIV) co-infections have remained a major public health concern worldwide, particularly in Southern Africa. Yet our understanding of the molecular interactions between the pathogens has remained poor due to lack of suitable preclinical models for such studies. We reviewed the use, this far, of mammalian cell culture models in HIV-MTB interaction studies. Studies have described the use of primary human cell cultures, including (1) monocyte-derived macrophage (MDM) fractions of peripheral blood mononuclear cell (PBMC), alveolar macrophages (AM), (2) cell lines such as the monocyte-derived macrophage cell line (U937), T lymphocyte cell lines (CEMx174, ESAT-6-specific CD4(+) T-cells) and an alveolar epithelial cell line (A549) and (3) special models such as stem cells, three dimensional (3D) or organoid cell models (including a blood-brain barrier cell model) in HIV-MTB interaction studies...
September 2016: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/27576565/derivation-of-intestinal-organoids-from-human-induced-pluripotent-stem-cells-for-use-as-an-infection-system
#18
Jessica L Forbester, Nicholas Hannan, Ludovic Vallier, Gordon Dougan
Intestinal human organoids (iHOs) provide an effective system for studying the intestinal epithelium and its interaction with various stimuli. By using combinations of different signaling factors, human induced pluripotent stem cells (hIPSCs) can be driven to differentiate down the intestinal lineage. Here, we describe the process for this differentiation, including the derivation of hindgut from hIPSCs, embedding hindgut into a pro-intestinal culture system and passaging the resulting iHOs. We then describe how to carry out microinjections to introduce bacteria to the apical side of the intestinal epithelial cells (IECs)...
August 31, 2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27571349/identification-of-small-molecule-inhibitors-of-zika-virus-infection-and-induced-neural-cell-death-via-a-drug-repurposing-screen
#19
Miao Xu, Emily M Lee, Zhexing Wen, Yichen Cheng, Wei-Kai Huang, Xuyu Qian, Julia Tcw, Jennifer Kouznetsova, Sarah C Ogden, Christy Hammack, Fadi Jacob, Ha Nam Nguyen, Misha Itkin, Catherine Hanna, Paul Shinn, Chase Allen, Samuel G Michael, Anton Simeonov, Wenwei Huang, Kimberly M Christian, Alison Goate, Kristen J Brennand, Ruili Huang, Menghang Xia, Guo-Li Ming, Wei Zheng, Hongjun Song, Hengli Tang
In response to the current global health emergency posed by the Zika virus (ZIKV) outbreak and its link to microcephaly and other neurological conditions, we performed a drug repurposing screen of ∼6,000 compounds that included approved drugs, clinical trial drug candidates and pharmacologically active compounds; we identified compounds that either inhibit ZIKV infection or suppress infection-induced caspase-3 activity in different neural cells. A pan-caspase inhibitor, emricasan, inhibited ZIKV-induced increases in caspase-3 activity and protected human cortical neural progenitors in both monolayer and three-dimensional organoid cultures...
October 2016: Nature Medicine
https://www.readbyqxmd.com/read/27566565/epithelial-mesenchymal-transition-and-nuclear-%C3%AE-catenin-induced-by-conditional-intestinal-disruption-of-cdh1-with-apc-is-e-cadherin-ec1-domain-dependent
#20
Julia Matheson, Claudia Bühnemann, Emma J Carter, David Barnes, Hans-Jürgen Hoppe, Jennifer Hughes, Stephen Cobbold, James Harper, Hans Morreau, Mirvat Surakhy, A Bassim Hassan
Two important protein-protein interactions establish E-cadherin (Cdh1) in the adhesion complex; homophilic binding via the extra-cellular (EC1) domain and cytoplasmic tail binding to β-catenin. Here, we evaluate whether E-cadherin binding can inhibit β-catenin when there is loss of Adenomatous polyposis coli (APC) from the β-catenin destruction complex. Combined conditional loss of Cdh1 and Apc were generated in the intestine, intestinal adenoma and adenoma organoids. Combined intestinal disruption (Cdh1fl/flApcfl/flVil-CreERT2) resulted in lethality, breakdown of the intestinal barrier, increased Wnt target gene expression and increased nuclear β-catenin localization, suggesting that E-cadherin inhibits β-catenin...
October 25, 2016: Oncotarget
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