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https://www.readbyqxmd.com/read/27921262/a-new-era-of-disease-modeling-and-drug-discovery-using-induced-pluripotent-stem-cells
#1
REVIEW
Wonhee Suh
In 2006, Shinya Yamanaka first reported that in vitro reprogramming of somatic cells toward pluripotency was achieved by simple induction of specific transcription factors. Induced pluripotent stem cell (iPSC) technology has since revolutionized the ways in which we explore the mechanisms of human diseases and develop therapeutics. Here, I describe the recent advances in human iPSC-based disease modeling and drug discovery and discuss the current challenges. Additionally, I outline potential future applications of human iPSCs in classifying patients based on their response to drugs in clinical trials and elucidating optimal patient-specific therapeutic strategies, which will contribute to reduced attrition rates and the development of precision medicine...
December 5, 2016: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/27916776/favorable-clinical-outcomes-of-transcatheter-aortic-valve-implantation-in-japanese-patients%C3%A3-first-report-from-the-post-approval-k-tavi-registry
#2
Shinya Takimoto, Naritatsu Saito, Kenji Minakata, Shinichi Shirai, Akihiro Isotani, Yoshio Arai, Michiya Hanyu, Tatsuhiko Komiya, Takeshi Shimamoto, Tsuyoshi Goto, Yasushi Fuku, Natsuhiko Ehara, Yutaka Furukawa, Tadaaki Koyama, Atsuhi Nagasawa, Toshihiro Tamura, Makoto Miyake, Kazuo Yamanaka, Hisashi Sakaguchi, Koichiro Murata, Tomoya Onodera, Fumio Yamazaki, Masanao Nakai, Tomohiko Taniguchi, Ryuzo Sakata, Takeshi Kimura
BACKGROUND: Very limited data exist on the outcomes of transcatheter aortic valve implantation (TAVI) since Japanese marketing approval of the first TAVI device.Methods and Results:The Kyoto University-related hospital Transcatheter Aortic Valve Implantation (K-TAVI) registry includes prospectively collected data from 6 participating hospitals in Japan. We included 302 patients with severe aortic stenosis who underwent TAVI using the SAPIEN XT balloon-expandable valve via transfemoral (TF; n=203, 67%) or transapical (TA; n=99, 33%) approach between October 2013 and September 2015...
December 3, 2016: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/27794120/bmp-smad-id-promotes-reprogramming-to-pluripotency-by-inhibiting-p16-ink4a-dependent-senescence
#3
Yohei Hayashi, Edward C Hsiao, Salma Sami, Mariselle Lancero, Christopher R Schlieve, Trieu Nguyen, Koyori Yano, Ayako Nagahashi, Makoto Ikeya, Yoshihisa Matsumoto, Ken Nishimura, Aya Fukuda, Koji Hisatake, Kiichiro Tomoda, Isao Asaka, Junya Toguchida, Bruce R Conklin, Shinya Yamanaka
Fibrodysplasia ossificans progressiva (FOP) patients carry a missense mutation in ACVR1 [617G > A (R206H)] that leads to hyperactivation of BMP-SMAD signaling. Contrary to a previous study, here we show that FOP fibroblasts showed an increased efficiency of induced pluripotent stem cell (iPSC) generation. This positive effect was attenuated by inhibitors of BMP-SMAD signaling (Dorsomorphin or LDN1931890) or transducing inhibitory SMADs (SMAD6 or SMAD7). In normal fibroblasts, the efficiency of iPSC generation was enhanced by transducing mutant ACVR1 (617G > A) or SMAD1 or adding BMP4 protein at early times during the reprogramming...
November 15, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27768780/over-expression-of-nanos3-and-dazl-in-human-embryonic-stem-cells
#4
Sarita Panula, Ahmed Reda, Jan-Bernd Stukenborg, Cyril Ramathal, Meena Sukhwani, Halima Albalushi, Daniel Edsgärd, Michiko Nakamura, Olle Söder, Kyle E Orwig, Shinya Yamanaka, Renee A Reijo Pera, Outi Hovatta
The mechanisms underlying human germ cell development are largely unknown, partly due to the scarcity of primordial germ cells and the inaccessibility of the human germline to genetic analysis. Human embryonic stem cells can differentiate to germ cells in vitro and can be genetically modified to study the genetic requirements for germ cell development. Here, we studied NANOS3 and DAZL, which have critical roles in germ cell development in several species, via their over expression in human embryonic stem cells using global transcriptional analysis, in vitro germ cell differentiation, and in vivo germ cell formation assay by xenotransplantation...
2016: PloS One
https://www.readbyqxmd.com/read/27764147/patient-specific-human-induced-pluripotent-stem-cell-model-assessed-with-electrical-pacing-validates-s107-as-a-potential-therapeutic-agent-for-catecholaminergic-polymorphic-ventricular-tachycardia
#5
Kenichi Sasaki, Takeru Makiyama, Yoshinori Yoshida, Yimin Wuriyanghai, Tsukasa Kamakura, Suguru Nishiuchi, Mamoru Hayano, Takeshi Harita, Yuta Yamamoto, Hirohiko Kohjitani, Sayako Hirose, Jiarong Chen, Mihoko Kawamura, Seiko Ohno, Hideki Itoh, Ayako Takeuchi, Satoshi Matsuoka, Masaru Miura, Naokata Sumitomo, Minoru Horie, Shinya Yamanaka, Takeshi Kimura
INTRODUCTION: Human induced pluripotent stem cells (hiPSCs) offer a unique opportunity for disease modeling. However, it is not invariably successful to recapitulate the disease phenotype because of the immaturity of hiPSC-derived cardiomyocytes (hiPSC-CMs). The purpose of this study was to establish and analyze iPSC-based model of catecholaminergic polymorphic ventricular tachycardia (CPVT), which is characterized by adrenergically mediated lethal arrhythmias, more precisely using electrical pacing that could promote the development of new pharmacotherapies...
2016: PloS One
https://www.readbyqxmd.com/read/27738243/autotaxin-mediated-lipid-signaling-intersects-with-lif-and-bmp-signaling-to-promote-the-naive-pluripotency-transcription-factor-program
#6
Cody Kime, Masayo Sakaki-Yumoto, Leeanne Goodrich, Yohei Hayashi, Salma Sami, Rik Derynck, Michio Asahi, Barbara Panning, Shinya Yamanaka, Kiichiro Tomoda
Developmental signaling molecules are used for cell fate determination, and understanding how their combinatorial effects produce the variety of cell types in multicellular organisms is a key problem in biology. Here, we demonstrate that the combination of leukemia inhibitory factor (LIF), bone morphogenetic protein 4 (BMP4), lysophosphatidic acid (LPA), and ascorbic acid (AA) efficiently converts mouse primed pluripotent stem cells (PSCs) into naive PSCs. Signaling by the lipid LPA through its receptor LPAR1 and downstream effector Rho-associated protein kinase (ROCK) cooperated with LIF signaling to promote this conversion...
November 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27696909/generation-of-induced-pluripotent-stem-cells-with-substitutes-for-yamanaka-s-four-transcription-factors
#7
Xiong Xiao, Nan Li, Dapeng Zhang, Bo Yang, Hongmei Guo, Yuemin Li
Induced pluripotent stem cells (iPSCs) share many characteristics with embryonic stem cells, but lack ethical controversy. They provide vast opportunities for disease modeling, pathogenesis understanding, therapeutic drug development, toxicology, organ synthesis, and treatment of degenerative disease. However, this procedure also has many potential challenges, including a slow generation time, low efficiency, partially reprogrammed colonies, as well as somatic coding mutations in the genome. Pioneered by Shinya Yamanaka's team in 2006, iPSCs were first generated by introducing four transcription factors: Oct 4, Sox 2, Klf 4, and c-Myc (OSKM)...
October 2016: Cellular Reprogramming
https://www.readbyqxmd.com/read/27696238/embryonic-kidney-function-in-a-chronic-renal-failure-model-in-rodents
#8
Eisuke Fujimoto, Shuichiro Yamanaka, Sho Kurihara, Susumu Tajiri, Luna Izuhara, Yuichi Katsuoka, Shinya Yokote, Kei Matsumoto, Eiji Kobayashi, Hirotaka James Okano, Tatsuya Chikaraishi, Takashi Yokoo
BACKGROUND: Rapid advancements have been made in alternative treatments for renal diseases. Our goal for renal regeneration is to establish a kidney graft derived from human embryonic tissues. In this study, we investigated the effects of host renal failure on the structure and activity of transplanted embryonic kidney and bladder, and found that diuretics effectively induced urine production in the transplanted kidney. METHODS: Uremic conditions were reproduced using a 5/6 renal infarction rat model...
September 30, 2016: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/27610558/ips-cells-10-years-later
#9
(no author information available yet)
In 2006, Takahashi and Yamanaka reported the breakthrough discovery of induction of pluripotent stem cells from fibroblasts by a combination of defined factors. Ten years later, Cell editor João Monteiro brings together Shinya Yamanaka and Hans Schöler, one the original reviewers of the landmark study, to revisit the history behind the paper and its long-lasting legacy.
September 8, 2016: Cell
https://www.readbyqxmd.com/read/27608814/microrna-302-switch-to-identify-and-eliminate-undifferentiated-human-pluripotent-stem-cells
#10
Callum J C Parr, Shota Katayama, Kenji Miki, Yi Kuang, Yoshinori Yoshida, Asuka Morizane, Jun Takahashi, Shinya Yamanaka, Hirohide Saito
The efficiency of pluripotent stem cell differentiation is highly variable, often resulting in heterogeneous populations that contain undifferentiated cells. Here we developed a sensitive, target-specific, and general method for removing undesired cells before transplantation. MicroRNA-302a-5p (miR-302a) is highly and specifically expressed in human pluripotent stem cells and gradually decreases to basal levels during differentiation. We synthesized a new RNA tool, miR-switch, as a live-cell reporter mRNA for miR-302a activity that can specifically detect human induced pluripotent stem cells (hiPSCs) down to a spiked level of 0...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27476965/epigenetic-variation-between-human-induced-pluripotent-stem-cell-lines-is-an-indicator-of-differentiation-capacity
#11
Masatoshi Nishizawa, Kazuhisa Chonabayashi, Masaki Nomura, Azusa Tanaka, Masahiro Nakamura, Azusa Inagaki, Misato Nishikawa, Ikue Takei, Akiko Oishi, Koji Tanabe, Mari Ohnuki, Hidaka Yokota, Michiyo Koyanagi-Aoi, Keisuke Okita, Akira Watanabe, Akifumi Takaori-Kondo, Shinya Yamanaka, Yoshinori Yoshida
Variation in the differentiation capacity of induced pluripotent stem cells (iPSCs) to specific lineages is a significant concern for their use in clinical applications and disease modeling. To identify factors that affect differentiation capacity, we performed integration analyses between hematopoietic differentiation performance and molecular signatures such as gene expression, DNA methylation, and chromatin status, using 35 human iPSC lines and four ESC lines. Our analyses revealed that hematopoietic commitment of PSCs to hematopoietic precursors correlates with IGF2 expression level, which in turn depends on signaling-dependent chromatin accessibility at mesendodermal genes...
September 1, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/27418197/identification-of-mmp1-as-a-novel-risk-factor-for-intracranial-aneurysms-in-adpkd-using-ipsc-models
#12
Tomonaga Ameku, Daisuke Taura, Masakatsu Sone, Tomohiro Numata, Masahiro Nakamura, Fumihiko Shiota, Taro Toyoda, Satoshi Matsui, Toshikazu Araoka, Tetsuhiko Yasuno, Shin-Ichi Mae, Hatasu Kobayashi, Naoya Kondo, Fumiyo Kitaoka, Naoki Amano, Sayaka Arai, Tomoko Ichisaka, Norio Matsuura, Sumiko Inoue, Takuya Yamamoto, Kazutoshi Takahashi, Isao Asaka, Yasuhiro Yamada, Yoshifumi Ubara, Eri Muso, Atsushi Fukatsu, Akira Watanabe, Yasunori Sato, Tatsutoshi Nakahata, Yasuo Mori, Akio Koizumi, Kazuwa Nakao, Shinya Yamanaka, Kenji Osafune
Cardiovascular complications are the leading cause of death in autosomal dominant polycystic kidney disease (ADPKD), and intracranial aneurysm (ICA) causing subarachnoid hemorrhage is among the most serious complications. The diagnostic and therapeutic strategies for ICAs in ADPKD have not been fully established. We here generated induced pluripotent stem cells (iPSCs) from seven ADPKD patients, including four with ICAs. The vascular cells differentiated from ADPKD-iPSCs showed altered Ca(2+) entry and gene expression profiles compared with those of iPSCs from non-ADPKD subjects...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27335261/screening-of-human-cdna-library-reveals-two-differentiation-related-genes-hhex-and-hlx-as-promoters-of-early-phase-reprogramming-toward-pluripotency
#13
Tatsuya Yamakawa, Yoshiko Sato, Yasuko Matsumura, Yukiko Kobayashi, Yoshifumi Kawamura, Naoki Goshima, Shinya Yamanaka, Keisuke Okita
Gene screenings have identified a number of reprogramming factors that induce pluripotency from somatic cells. However, the screening methods have mostly considered only factors that maintain pluripotency in embryonic stem cells, ignoring a potentially long list of other contributing factors involved. To expand the search, we developed a new screening method that examined 2,008 human genes in the generation of human induced pluripotent stem cells (iPSCs), including not only pluripotent genes but also differentiation-related genes that suppress pluripotency...
June 22, 2016: Stem Cells
https://www.readbyqxmd.com/read/27271561/correction-adipose-tissue-derived-mesenchymal-stem-cells-in-long-term-dialysis-patients-display-downregulation-of-pcaf-expression-and-poor-angiogenesis-activation
#14
Shuichiro Yamanaka, Shinya Yokote, Akifumi Yamada, Yuichi Katsuoka, Luna Izuhara, Yohta Shimada, Nobuo Omura, Hirotaka James Okano, Takao Ohki, Takashi Yokoo
[This corrects the article DOI: 10.1371/journal.pone.0102311.].
2016: PloS One
https://www.readbyqxmd.com/read/27212953/establishment-of-human-neural-progenitor-cells-from-human-induced-pluripotent-stem-cells-with-diverse-tissue-origins
#15
Hayato Fukusumi, Tomoko Shofuda, Yohei Bamba, Atsuyo Yamamoto, Daisuke Kanematsu, Yukako Handa, Keisuke Okita, Masaya Nakamura, Shinya Yamanaka, Hideyuki Okano, Yonehiro Kanemura
Human neural progenitor cells (hNPCs) have previously been generated from limited numbers of human induced pluripotent stem cell (hiPSC) clones. Here, 21 hiPSC clones derived from human dermal fibroblasts, cord blood cells, and peripheral blood mononuclear cells were differentiated using two neural induction methods, an embryoid body (EB) formation-based method and an EB formation method using dual SMAD inhibitors (dSMADi). Our results showed that expandable hNPCs could be generated from hiPSC clones with diverse somatic tissue origins...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27180609/imaging-of-bacterial-multicellular-behaviour-in-biofilms-in-liquid-by-atmospheric-scanning-electron-microscopy
#16
Shinya Sugimoto, Ken-Ichi Okuda, Reina Miyakawa, Mari Sato, Ken-Ichi Arita-Morioka, Akio Chiba, Kunitoshi Yamanaka, Teru Ogura, Yoshimitsu Mizunoe, Chikara Sato
Biofilms are complex communities of microbes that attach to biotic or abiotic surfaces causing chronic infectious diseases. Within a biofilm, microbes are embedded in a self-produced soft extracellular matrix (ECM), which protects them from the host immune system and antibiotics. The nanoscale visualisation of delicate biofilms in liquid is challenging. Here, we develop atmospheric scanning electron microscopy (ASEM) to visualise Gram-positive and -negative bacterial biofilms immersed in aqueous solution. Biofilms cultured on electron-transparent film were directly imaged from below using the inverted SEM, allowing the formation of the region near the substrate to be studied at high resolution...
2016: Scientific Reports
https://www.readbyqxmd.com/read/26968984/when-myc-s-asleep-embryonic-stem-cells-are-dormant
#17
Masato Nakagawa, Peter Karagiannis, Shinya Yamanaka
No abstract text is available yet for this article.
April 15, 2016: EMBO Journal
https://www.readbyqxmd.com/read/26949256/sox2-o-glcnacylation-alters-its-protein-protein-interactions-and-genomic-occupancy-to-modulate-gene-expression-in-pluripotent-cells
#18
Samuel A Myers, Sailaja Peddada, Nilanjana Chatterjee, Tara Friedrich, Kiichrio Tomoda, Gregor Krings, Sean Thomas, Jason Maynard, Michael Broeker, Matthew Thomson, Katherine Pollard, Shinya Yamanaka, Alma L Burlingame, Barbara Panning
The transcription factor SOX2 is central in establishing and maintaining pluripotency. The processes that modulate SOX2 activity to promote pluripotency are not well understood. Here, we show SOX2 is O-GlcNAc modified in its transactivation domain during reprogramming and in mouse embryonic stem cells (mESCs). Upon induction of differentiation SOX2 O-GlcNAcylation at serine 248 is decreased. Replacing wild type with an O-GlcNAc-deficient SOX2 (S248A) increases reprogramming efficiency. ESCs with O-GlcNAc-deficient SOX2 exhibit alterations in gene expression...
2016: ELife
https://www.readbyqxmd.com/read/26883003/a-decade-of-transcription-factor-mediated-reprogramming-to-pluripotency
#19
REVIEW
Kazutoshi Takahashi, Shinya Yamanaka
The past 10 years have seen great advances in our ability to manipulate cell fate, including the induction of pluripotency in vitro to generate induced pluripotent stem cells (iPSCs). This process proved to be remarkably simple from a technical perspective, only needing the host cell and a defined cocktail of transcription factors, with four factors - octamer-binding protein 3/4 (OCT3/4), SOX2, Krüppel-like factor 4 (KLF4) and MYC (collectively referred to as OSKM) - initially used. The mechanisms underlying transcription factor-mediated reprogramming are still poorly understood; however, several mechanistic insights have recently been obtained...
March 2016: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/26849306/timeline-ipscs-the-first-decade
#20
Sheila Chari, Steve Mao
Research into induced pluripotent stem cells (iPSCs) has expanded at a remarkable pace in the decade since Shinya Yamanaka and Kazutoshi Takahashi first reported their groundbreaking discovery in 2006. This Timeline highlights the key events in the development of this field, including basic insights into the production of iPSCs and how they have been applied to improve our understanding and treatment of human disease. To view this Timeline, open or download the PDF. You can also listen to the associated interview with Debbie Sweet, Editor of Cell Stem Cell, and Elena Porro, Editor of Cell...
February 4, 2016: Cell Stem Cell
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