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https://www.readbyqxmd.com/read/28541280/a-quantitative-csmart-assay-for-noninvasive-prenatal-screening-of-autosomal-recessive-nonsyndromic-hearing-loss-caused-by-gjb2-and-slc26a4-mutations
#1
Mingyu Han, Zhifeng Li, Wenlu Wang, Shasha Huang, Yanping Lu, Zhiying Gao, Longxia Wang, Dongyang Kang, Linwei Li, Yiqian Liu, Mengnan Xu, David S Cram, Pu Dai
PurposeThe aim of this study was to assess the performance of a noninvasive prenatal screening (NIPS) assay for accurate fetal genotyping of pregnancies at genetic risk for autosomal recessive nonsyndromic hearing loss (ARNSHL).MethodsA total of 80 pregnant couples carrying known mutations in either the GJB2 or SLC26A4 genes associated with a risk for ARNSHL were recruited to the study. Fetal amniocyte samples were genotyped by invasive prenatal screening (IPS), whereas the cell-free fetal DNA present in maternal plasma samples was genotyped using a novel NIPS method based on circulating single-molecule amplification and resequencing technology (cSMART)...
May 25, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28539639/the-absence-of-interferon-%C3%AE-promotor-stimulator-1-ips-1-predisposes-to-bronchiolitis-and-asthma-like-pathology-in-response-to-pneumoviral-infection-in-mice
#2
Jennifer Simpson, Jason P Lynch, Zhixuan Loh, Vivian Zhang, Rhiannon B Werder, Kirsten Spann, Simon Phipps
Respiratory syncytial virus (RSV)-bronchiolitis is a major cause of infant morbidity and mortality and a risk factor for subsequent asthma. We showed previously that toll-like receptor (TLR)7 in plasmacytoid dendritic cells (pDCs) is critical for protection against bronchiolitis and asthma in mice infected with pneumonia virus of mice (PVM), the mouse homolog of RSV. This lack of redundancy was unexpected as interferon-β promotor stimulator-1 (IPS-1) signalling, downstream of RIG-I-like receptor (RLR) and not TLR7 activation, contributes to host defence in hRSV-inoculated adult mice...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28539554/investigation-of-the-pathogenesis-of-autoimmune-diseases-by-ips-cells
#3
Bunki Natsumoto, Hirofumi Shoda, Keishi Fujio, Makoto Otsu, Kazuhiko Yamamoto
  The pluripotent stem cells have a self-renewal ability and can be differentiated into theoretically all of cell types. The induced pluripotent stem (iPS) cells overcame the ethical problems of the human embryonic stem (ES) cell, and enable pathologic analysis of intractable diseases and drug discovery. The in vitro disease model using disease-specific iPS cells enables repeated analyses of human cells without influence of environment factors. Even though autoimmune diseases are polygenic diseases, autoimmune disease-specific iPS cells are thought to be a promising tool for analyzing the pathogenesis of the diseases and drug discovery in future...
2017: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28530648/mechanism-of-human-somatic-reprogramming-to-ips-cell
#4
Rika Teshigawara, Junkwon Cho, Masahiro Kameda, Takashi Tada
Somatic reprogramming to induced pluripotent stem cells (iPSC) was realized in the year 2006 in mice, and in 2007 in humans, by transiently forced expression of a combination of exogenous transcription factors. Human and mouse iPSCs are distinctly reprogrammed into a 'primed' and a 'naïve' state, respectively. In the last decade, puzzle pieces of somatic reprogramming have been collected with difficulty. Collectively, dissecting reprogramming events and identification of the hallmark of sequentially activated/silenced genes have revealed mouse somatic reprogramming in fragments, but there is a long way to go toward understanding the molecular mechanisms of human somatic reprogramming, even with developing technologies...
May 22, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28529336/stem-cells-the-different-flavours-of-ips-cells
#5
Katharine H Wrighton
No abstract text is available yet for this article.
May 22, 2017: Nature Reviews. Genetics
https://www.readbyqxmd.com/read/28526755/the-matrix-protein-tiggrin-regulates-plasmatocyte-maturation-in-drosophila-larva
#6
Chen U Zhang, Ken M Cadigan
The lymph gland (LG) is a major source of hematopoiesis during Drosophila development. In this tissue, prohemocytes differentiate into multiple lineages including macrophage-like plasmatocytes, which comprise the vast majority of mature hemocytes. Previous studies have uncovered genetic pathways that regulate prohemocyte maintenance and some cell fate choices between hemocyte lineages. However, less is known about how the plasmatocyte pool of the LG is established and matures. Here we report that Tiggrin, a matrix protein expressed in the LG, is a specific regulator of plasmatocyte maturation...
May 19, 2017: Development
https://www.readbyqxmd.com/read/28494936/functional-analysis-of-dendritic-cells-generated-from-t-ipscs-from-cd4-t-cell-clones-of-sj%C3%A3-gren-s-syndrome
#7
Mana Iizuka-Koga, Hiromitsu Asashima, Miki Ando, Chen-Yi Lai, Shinji Mochizuki, Mahito Nakanishi, Toshinobu Nishimura, Hiroto Tsuboi, Tomoya Hirota, Hiroyuki Takahashi, Isao Matsumoto, Makoto Otsu, Takayuki Sumida
Although it is important to clarify the pathogenic functions of T cells in human samples, their examination is often limited due to difficulty in obtaining sufficient numbers of dendritic cells (DCs), used as antigen-presenting cells, especially in autoimmune diseases. We describe the generation of DCs from induced pluripotent stem cells derived from T cells (T-iPSCs). We reprogrammed CD4+ T cell clones from a patient with Sjögren's syndrome (SS) into iPSCs, which were differentiated into DCs (T-iPS-DCs)...
May 9, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28491099/induction-of-pluripotent-stem-cells-from-a-manifesting-carrier-of-duchenne-muscular-dystrophy-and-characterization-of-their-x-inactivation-status
#8
Yuko Miyagoe-Suzuki, Takashi Nishiyama, Miho Nakamura, Asako Narita, Fusako Takemura, Satoru Masuda, Narihiro Minami, Kumiko Murayama, Hirofumi Komaki, Yu-Ichi Goto, Shin'ichi Takeda
Three to eight percent of female carriers of Duchenne muscular dystrophy (DMD) develop dystrophic symptoms ranging from mild muscle weakness to a rapidly progressive DMD-like muscular dystrophy due to skewed inactivation of X chromosomes during early development. Here, we generated human induced pluripotent stem cells (hiPSCs) from a manifesting female carrier using retroviral or Sendai viral (SeV) vectors and determined their X-inactivation status. Although manifesting carrier-derived iPS cells showed normal expression of human embryonic stem cell markers and formed well-differentiated teratomas in vivo, many hiPS clones showed bi-allelic expression of the androgen receptor (AR) gene and loss of X-inactivation-specific transcript and trimethyl-histone H3 (Lys27) signals on X chromosomes, suggesting that both X chromosomes of the hiPS cells are in an active state...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28476334/novel-spliced-variants-of-oct4-oct4c-and-oct4c1-with-distinct-expression-patterns-and-functions-in-pluripotent-and-tumor-cell-lines
#9
Mahshid Malakootian, Fatemeh Mirzadeh Azad, Parisa Naeli, Mohammad Pakzad, Youssef Fouani, Elham Taheri Bajgan, Hossein Baharvand, Seyed Javad Mowla
OCT4 is a major regulator of pluripotency which has several spliced variants and expressed pseudogenes. Here, we are reporting the existence of two additional novel spliced variants of OCT4, OCT4C and OCT4C1, which lack Exon1 (E1) but start at a novel exon (E0) located ∼14kb upstream of E2. OCT4C/C1 is highly expressed in ES and iPS cells, and their expression was sharply turned off, upon the induction of neural differentiation. The long non-coding RNA (lncRNA) PSORS1C3, is located ∼9kb downstream of the E0 of OCT4C/C1...
April 10, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28473859/myogenic-differentiation-from-myogenin-mutated-human-ips-cells-by-crispr-cas9
#10
Koki Higashioka, Noriko Koizumi, Hidetoshi Sakurai, Chie Sotozono, Takahiko Sato
It is well known that myogenic regulatory factors encoded by the Myod1 family of genes have pivotal roles in myogenesis, with partially overlapping functions, as demonstrated for the mouse embryo. Myogenin-mutant mice, however, exhibit severe myogenic defects without compensation by other myogenic factors. MYOGENIN might be expected to have an analogous function in human myogenic cells. To verify this hypothesis, we generated MYOGENIN-mutated human iPS cells by using CRISPR/Cas9 genome-editing technology. Our results suggest that MYOD1-independent or MYOD1-dependent mechanisms can compensate for the loss of MYOGENIN and that these mechanisms are likely to be crucial for regulating skeletal muscle differentiation and formation...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28466265/ips-cell-cultures-from-a-gerstmann-str%C3%A3-ussler-scheinker-patient-with-the-y218n-prnp-mutation-recapitulate-tau-pathology
#11
Andreu Matamoros-Angles, Lucía Mayela Gayosso, Yvonne Richaud-Patin, Angelique di Domenico, Cristina Vergara, Arnau Hervera, Amaya Sousa, Natalia Fernández-Borges, Antonella Consiglio, Rosalina Gavín, Rakel López de Maturana, Isidro Ferrer, Adolfo López de Munain, Ángel Raya, Joaquín Castilla, Rosario Sánchez-Pernaute, José Antonio Del Río
Gerstmann-Sträussler-Scheinker (GSS) syndrome is a fatal autosomal dominant neurodegenerative prionopathy clinically characterized by ataxia, spastic paraparesis, extrapyramidal signs and dementia. In some GSS familiar cases carrying point mutations in the PRNP gene, patients also showed comorbid tauopathy leading to mixed pathologies. In this study we developed an induced pluripotent stem (iPS) cell model derived from fibroblasts of a GSS patient harboring the Y218N PRNP mutation, as well as an age-matched healthy control...
May 2, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28465426/a-novel-agonist-of-the-trif-pathway-induces-a-cellular-state-refractory-to-replication-of-zika-chikungunya-and-dengue-viruses
#12
Kara M Pryke, Jinu Abraham, Tina M Sali, Bryan J Gall, Iris Archer, Andrew Liu, Shelly Bambina, Jason Baird, Michael Gough, Marita Chakhtoura, Elias K Haddad, Ilsa T Kirby, Aaron Nilsen, Daniel N Streblow, Alec J Hirsch, Jessica L Smith, Victor R DeFilippis
The ongoing concurrent outbreaks of Zika, Chikungunya, and dengue viruses in Latin America and the Caribbean highlight the need for development of broad-spectrum antiviral treatments. The type I interferon (IFN) system has evolved in vertebrates to generate tissue responses that actively block replication of multiple known and potentially zoonotic viruses. As such, its control and activation through pharmacological agents may represent a novel therapeutic strategy for simultaneously impairing growth of multiple virus types and rendering host populations resistant to virus spread...
May 2, 2017: MBio
https://www.readbyqxmd.com/read/28460880/transdifferentiation-and-reprogramming-overview-of-the-processes-their-similarities-and-differences
#13
REVIEW
Artur Cieślar-Pobuda, Viktoria Knoflach, Mikael V Ringh, Joachim Stark, Wirginia Likus, Krzysztof Siemianowicz, Saeid Ghavami, Andrzej Hudecki, Jason L Green, Marek J Łos
Reprogramming, or generation of induced pluripotent stem (iPS) cells (functionally similar to embryonic stem cells or ES cells) by the use of transcription factors (typically: Oct3/4, Sox2, c-Myc, Klf4) called "Yamanaka factors" (OSKM), has revolutionized regenerative medicine. However, factors used to induce stemness are also overexpressed in cancer. Both, ES cells and iPS cells cause teratoma formation when injected to tissues. This raises a safety concern for therapies based on iPS derivates. Transdifferentiation (lineage reprogramming, or -conversion), is a process in which one mature, specialized cell type changes into another without entering a pluripotent state...
April 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28447889/bone-marrow-as-a-hematopoietic-stem-cell-source-for-gene-therapy-in-sickle-cell-disease-evidence-from-rhesus-and-scd-patients
#14
Naoya Uchida, Atsushi Fujita, Matthew M Hsieh, Aylin C Bonifacino, Allen E Krouse, Mark E Metzger, Robert E Donahue, John F Tisdale
Steady state bone marrow (BM) is the preferred hematopoietic stem cell (HSC) source for gene therapy in sickle cell disease (SCD) due to the recognized risk of vaso-occlusive crisis during granulocyte colony-stimulating factor mobilization. We previously established clinically relevant HSC gene transfer in the rhesus model following transplantation of mobilized peripheral blood (PB) CD34(+) cells transduced with lentiviral vectors. In this study, we examined steady state bone marrow (BM) in the rhesus competitive repopulation model and demonstrate similar gene marking in vitro and in vivo, as compared with mobilized PB CD34(+) cells...
April 17, 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28442664/induction-of-neural-crest-cells-from-human-dental-pulp-derived-induced-pluripotent-stem-cells
#15
Eisuke Kawano, Taku Toriumi, Shinya Iguchi, Daigo Suzuki, Shuichi Sato, Masaki Honda
We previously generated induced pluripotent stem (iPS) cells from human dental pulp cells of deciduous teeth. Neural crest cells (NCCs) play a vital role in the development of the oral and maxillofacial region. Therefore, NCCs represent a cell source for bone, cartilage, and tooth-related tissue engineering. In this study, we examined whether iPS cells are capable of differentiating into NCCs through modification of the human embryonic stem cell protocol. First, iPS cells were dissociated into single cells and then reaggregated in low-cell-adhesion plates with neural induction medium for 8 days in suspension culture to form neurospheres...
2017: Biomedical Research
https://www.readbyqxmd.com/read/28440498/differentiation-of-human-induced-pluripotent-stem-cells-in-william-s-e-initiation-medium-supplemented-with-3%C3%A2-bromopyruvate-and-2%C3%A2-deoxy%C3%A2-d%C3%A2-glucose
#16
Minoru Tomizawa, Fuminobu Shinozaki, Yasufumi Motoyoshi, Takao Sugiyama, Shigenori Yamamoto, Naoki Ishige
Hepatocyte selection medium (HSM) is deprived of glucose and supplemented with galactose, and is based on Leibovitz's‑15 (L15) medium. HSM may promote the differentiation of human induced pluripotent stem (iPS) cells towards hepatocyte lineage. These culture conditions result in increased expression of galactokinase (GALK)‑1 and GALK2. However, iPS cells do not survive in HSM. Two potential alternatives to glucose deprivation are treatment with 3‑bromopyruvate (3BP), an analogue of pyruvate, and 2‑deoxy‑d‑glucose (2DG), an analogue of glucose...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28434942/ipsc-derived-regulatory-dendritic-cells-inhibit-allograft-rejection-by%C3%A2-generating-alloantigen-specific-regulatory-t-cells
#17
Songjie Cai, Jiangang Hou, Masayuki Fujino, Qi Zhang, Naotsugu Ichimaru, Shiro Takahara, Ryoko Araki, Lina Lu, Ji-Mei Chen, Jian Zhuang, Ping Zhu, Xiao-Kang Li
Regulatory dendritic cell (DCregs)-based immunotherapy is a potential therapeutic tool for transplant rejection. We generated DCregs from murine induced pluripotent stem cells (iPSCs), which could remain in a "stable immature stage" even under strong stimulation. Harnessing this characteristic, we hypothesized that iPS-DCregs worked as a negative vaccine to generate regulatory T cells (Tregs), and induced donor-specific allograft acceptance. We immunized naive CBA (H-2K(k)) mice with B6 (H-2K(b)) iPS-DCregs and found that Tregs (CD4(+)CD25(+)FOXP3(+)) significantly increased in CBA splenocytes...
May 9, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28434791/neuronal-cells-derived-from-human-induced-pluripotent-stem-cells-as-a-functional-tool-of-melanocortin-system
#18
Nobuko Yamada-Goto, Yukari Ochi, Goro Katsuura, Yui Yamashita, Ken Ebihara, Michio Noguchi, Junji Fujikura, Daisuke Taura, Masakatsu Sone, Kiminori Hosoda, Paul E Gottschall, Kazuwa Nakao
BACKGROUND: The preparation of human neurons derived from human induced pluripotent stem (iPS) cells can serve as a potential tool for evaluating the physiological and pathophysiological properties of human neurons and for drug development. METHODS: In the present study, the functional activity in neuronal cells differentiated from human iPS cells was observed. RESULTS: The differentiated cells expressed mRNAs for classical neuronal markers (microtubule-associated protein 2, β-tubulin III, calbindin 1, synaptophysin and postsynaptic density protein 95) and for subunits of various excitatory and inhibitory transmitters (NR1, NR2A, NR2B, GABAA α1)...
April 7, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28426026/generation-of-multipotent-induced-cardiac-progenitor-cells-from-mouse-fibroblasts-and-potency-testing-in-ex-vivo-mouse-embryos
#19
Pratik A Lalit, Adriana M Rodriguez, Karen M Downs, Timothy J Kamp
Here we describe a protocol to generate expandable and multipotent induced cardiac progenitor cells (iCPCs) from mouse adult fibroblasts using forced expression of Mesp1, Tbx5, Gata4, Nkx2.5 and Baf60c (MTGNB) along with activation of Wnt and JAK/STAT signaling. This method does not use iPS cell factors and thus differs from cell activation and signaling-directed (CASD) reprogramming to cardiac progenitors. Our method is specific to direct CPC reprogramming, whereas CASD reprogramming can generate various cell types depending on culture conditions and raises the possibility of transitioning through a pluripotent cell state...
May 2017: Nature Protocols
https://www.readbyqxmd.com/read/28425064/a-pathway-to-personalizing-therapy-for-metastases-using-liver-on-a-chip-platforms
#20
A S Khazali, A M Clark, A Wells
Metastasis accounts for most cancer-related deaths. The majority of solid cancers, including those of the breast, colorectum, prostate and skin, metastasize at significant levels to the liver due to its hemodynamic as well as tumor permissive microenvironmental properties. As this occurs prior to detection and treatment of the primary tumor, we need to target liver metastases to improve patients' outcomes. Animal models, while proven to be useful in mechanistic studies, do not represent the heterogeneity of human population especially in drug metabolism lack proper human cell-cell interactions, and this gap between animals and humans results in costly and inefficient drug discovery...
April 19, 2017: Stem Cell Reviews
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