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https://www.readbyqxmd.com/read/29053954/spt6-gets-in-the-way-of-polycomb-to-promote-esc-pluripotency
#1
François Robert
Despite expressing high levels of Polycomb group proteins, embryonic stem cells (ESCs) are refractory to H3K27 trimethylation, notably at super-enhancers regulating key pluripotency genes. In this issue of Molecular Cell, Wang et al. (2017) report that the histone chaperone Spt6 prevents H3K27 trimethylation of key ESC super-enhancers.
October 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29052331/piwis-pirnas-and-retrotransposons-complex-battles-during-reprogramming-in-gametes-and-early-embryos
#2
REVIEW
S J Russell, L Stalker, J LaMarre
Gamete and embryo development are indispensable processes for successful reproduction. Cells involved in these processes acquire pluripotency, the ability to differentiate into multiple different cell types, through a series of events known as reprogramming that lead to profound changes in histone and DNA methylation. While essential for pluripotency, this epigenetic remodelling removes constraints that normally limit the expression of genomic sequences known as transposable elements (TEs). Unconstrained TE expression can lead to many deleterious consequences including infertility, so organisms have evolved complex and potent mechanistic arsenals to target and suppress TE expression during reprogramming...
October 2017: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/29051230/iphemap-an-atlas-of-phenotype-to-genotype-relationships-of-human-ipsc-models-of-neurological%C3%A2-diseases
#3
Ethan W Hollingsworth, Jacob E Vaughn, Josh C Orack, Chelsea Skinner, Jamil Khouri, Sofia B Lizarraga, Mark E Hester, Fumihiro Watanabe, Kenneth S Kosik, Jaime Imitola
Disease modeling with induced pluripotent stem cells (iPSCs) is creating an abundance of phenotypic information that has become difficult to follow and interpret. Here, we report a systematic analysis of research practices and reporting bias in neurological disease models from 93 published articles. We find heterogeneity in current research practices and a reporting bias toward certain diseases. Moreover, we identified 663 CNS cell-derived phenotypes from 243 patients and 214 controls, which varied by mutation type and developmental stage in vitro We clustered these phenotypes into a taxonomy and characterized these phenotype-genotype relationships to generate a phenogenetic map that revealed novel correlations among previously unrelated genes...
October 19, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29050935/the-l1-adhesion-molecule-normalizes-neuritogenesis-in-rett-syndrome-derived-neural-precursor-cells
#4
Myungsik Yoo, Cassiano Carromeu, Ohyoon Kwon, Alysson Muotri, Melitta Schachner
Therapeutic intervention is an important need in ameliorating the severe consequences of Rett Syndrome (RTT), a neurological disorder caused by mutations in the X-linked gene methyl-CpG-binding protein-2 (MeCP2). Following previously observed morphological defects in induced pluripotent stem cell (iPSC)-derived neurons obtained from female RTT patients, we hypothesized transfection with the L1 cell adhesion molecule (L1) could contribute to normalizing a pathological male cell system bearing a nonsense mutation of MeCP2...
October 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29050212/recombination-activating-gene-2-null-severe-combined-immunodeficient-pigs-and-mice-engraft-human-induced-pluripotent-stem-cells-differently
#5
Yun-Jung Choi, EunSu Kim, Abu Musa Md Talimur Reza, Kwonho Hong, Hyuk Song, Chankyu Park, Seong-Keun Cho, Kiho Lee, Randall S Prather, Jin-Hoi Kim
This study comparatively investigated the transcriptional, physiological, and phenotypic differences of the immune disorder between severe combined immunodeficient (SCID) mouse and pig models. We discovered that the recombination activating gene-2 (Rag-2) SCID mice, but not RAG-2 SCID pigs, showed intense, infrequent, and mild cluster of CD3(+)-, CD4(+)-, and CD8(+) signals respectively, suggesting that distinct species-specific effects exist. Furthermore, the expression of six relevant genes (NFATC1, CD79B, CD2, BLNK, FOXO1, and CD40) was more downregulated than that in the Rag-2 SCID mice, which provides a partial rationale for the death of T/B cells in the lymphoid organs of RAG-2 SCID pigs but not in Rag-2 SCID mice...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29048622/enhancement-of-cytotoxic-effects-of-gemcitabine-by-dclk1-inhibition-through-suppression-of-chk1-phosphorylation-in-human-pancreatic-cancer-cells
#6
Daichi Kawamura, Yoshihiro Takemoto, Arata Nishimoto, Koji Ueno, Tohru Hosoyama, Bungo Shirasawa, Toshiki Tanaka, Naruji Kugimiya, Eijiro Harada, Kimikazu Hamano
Although gemcitabine (GEM) is frequently used in the treatment of pancreatic cancer, the effects are limited. To increase the inhibitory effect of GEM, the identification of a molecular target is needed. Recent studies have revealed that doublecortin-like kinase 1 (Dclk1) positively regulates tumor growth, invasion, metastasis, factors related to epithelial-mesenchymal transition (EMT), pluripotency, angiogenesis, and anti-apoptosis in pancreatic cancer cells. Therefore, Dclk1 is a potential therapeutic target for pancreatic cancer...
September 20, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29048434/common-microrna-mrna-interactions-exist-among-distinct-porcine-ipsc-lines-independent-of-their-metastable-pluripotent-states
#7
Shiqiang Zhang, Youlong Xie, Hongxia Cao, Huayan Wang
Previous evidences have proved that porcine-induced pluripotent stem cells (piPSCs) could be induced to distinctive metastable pluripotent states. This raises the issue of whether there is a common transcriptomic profile existing among the piPSC lines at distinctive state. In this study, we performed conjoint analysis of small RNA-seq and mRNA-seq for three piPSC lines which represent LIF dependence, FGF2 dependence and LFB2i dependence, respectively. Interestingly, we found there are 16 common microRNAs which potentially target 13 common mRNAs among the three piPSC lines...
August 31, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29047401/correction-to-potent-and-reversible-lentiviral-vector-restriction-in-murine-induced-pluripotent-stem-cells
#8
Franziska K Geis, Melanie Galla, Dirk Hoffmann, Johannes Kuehle, Daniela Zychlinski, Tobias Maetzig, Juliane W Schott, Adrian Schwarzer, Christine Goffinet, Stephen P Goff, Axel Schambach
The authors wish to apologize for an error within the scale bar of the microarray heatmap in Additional File 5 of the supplementary information. Two values were incorrectly displayed on the scale bar (11 instead of 10 and 13 instead of 12).
October 18, 2017: Retrovirology
https://www.readbyqxmd.com/read/29047282/a-new-cell-separation-method-based-on-antibody-immobilized-nanoneedle-arrays-for-the-detection-of-intracellular-markers
#9
Ryuzo Kawamura, Minami Miyazaki, Keita Shimizu, Yuta Matsumoto, Yaron R Silberberg, Ramachandra Rao Sathuluri, Masumi Iijima, Shun'ichi Kuroda, Futoshi Iwata, Takeshi Kobayashi, Chikashi Nakamura
Focusing on intracellular targets, we propose a new cell separation technique based on a nanoneedle array (NNA) device, which allows simultaneous insertion of multiple needles into multiple cells. The device is designed to target and lift ('fish') individual cells from a mixed population of cells on a substrate using an antibody-functionalized NNA. The mechanics underlying this approach were validated by force analysis using an atomic force microscope. Accurate high-throughput separation was achieved using one-to-one contacts between the nanoneedles and the cells by preparing a single-cell array in which the positions of the cells were aligned with 10,000 nanoneedles in the NNA...
October 19, 2017: Nano Letters
https://www.readbyqxmd.com/read/29047185/pluripotent-stem-cell-derived-haematopoietic-progenitors-are-unable-to-downregulate-key-emt-associated-mirnas
#10
Ellie Meader, Tomas Barta, Dario Melguzo-Sanchis, Katarzyna Tilgner, David Montaner, Ashraf A El-Harouni, Lyle Armstrong, Majlinda Lako
Haematopoietic stem cells derived from pluripotent stem cells could be used as an alternative to bone marrow transplants. Deriving these has been a long-term goal for researchers. However, the success of these efforts has been limited, with the cells produced able to engraft in the bone marrow of recipient animals only in very low numbers. There is evidence that defects in the migratory and homing capacity of the cells are due to mis-regulation of miRNA expression, and are responsible for their failure to engraft...
October 19, 2017: Stem Cells
https://www.readbyqxmd.com/read/29047024/generation-of-photoreceptor-precursors-from-mouse-embryonic-stem-cells
#11
Amy Q Lu, Colin J Barnstable
Embryonic stem cell (ESC) differentiation can be used to model development and to produce transplantable cells of the desired phenotype. ESCs can reproducibly generate retinal cells but the derivation of photoreceptor precursors is variable and depends on an array of exogenous factors and intrinsic cell-cell interactions. In this work, we have defined the use of exogenous signaling factors, dissociation, and adherent versus 3-dimensional (3D) conditions on the derivation of retinal cells from pluripotent mouse ESCs...
October 18, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/29045016/liquid-crystalline-networks-toward-regenerative-medicine-and-tissue-repair
#12
Daniele Martella, Paolo Paoli, Josè M Pioner, Leonardo Sacconi, Raffaele Coppini, Lorenzo Santini, Matteo Lulli, Elisabetta Cerbai, Diederik S Wiersma, Corrado Poggesi, Cecilia Ferrantini, Camilla Parmeggiani
The communication reports the use of liquid crystalline networks (LCNs) for engineering tissue cultures with human cells. Their ability as cell scaffolds for different cell lines is demonstrated. Preliminary assessments of the material biocompatibility are performed on human dermal fibroblasts and murine muscle cells (C2C12), demonstrating that coatings or other treatments are not needed to use the acrylate-based materials as support. Moreover, it is found that adherent C2C12 cells undergo differentiation, forming multinucleated myotubes, which show the typical elongated shape, and contain bundles of stress fibers...
October 17, 2017: Small
https://www.readbyqxmd.com/read/29044527/effect-of-the-combined-use-of-enamel-matrix-derivative-and-atelocollagen-sponge-scaffold-on-osteoblastic-differentiation-of-mouse-induced-pluripotent-stem-cells-in-vitro
#13
Y Hisanaga, E Suzuki, H Aoki, M Sato, A Saito, A Saito, T Azuma
BACKGROUND AND OBJECTIVE: Induced pluripotent stem cells (iPSCs) are a candidate cell source in periodontal regenerative therapy. Enamel matrix derivative (EMD) has been shown to regenerate periodontal tissues, and atelocollagen sponge (ACS) is considered a suitable scaffold or carrier for growth factors. This study aimed to investigate the effect of combined use of EMD and an ACS scaffold on cell behaviors and differentiation of mouse iPSCs (miPSCs) in vitro. MATERIAL AND METHODS: Following embryonic body formation from miPSCs, dissociated cells (miPS-EB-derived cells) were seeded onto ACS with or without EMD, and cultured in osteoblast differentiation medium...
October 17, 2017: Journal of Periodontal Research
https://www.readbyqxmd.com/read/29044512/differences-in-definitive-endoderm-induction-approaches-using-growth-factors-and-small-molecules
#14
Mariia S Bogacheva, Sofia Khan, Liisa K Kanninen, Marjo Yliperttula, Alan W Leung, Yan-Ru Lou
Definitive endoderm (DE) is the first stage of human pluripotent stem cell (hPSC) differentiation into hepatocyte-like cells. Developing human liver cell models for pharmaceutical applications is highly demanding. Due to the vast number of existing protocols to generate DE cells from hPSCs, we aimed to compare the specificity and efficiency of selected published differentiation conditions. We differentiated two hPSC lines (induced PSC and embryonic stem cell) to DE cells on Matrigel matrix using growth factors (Activin A and Wnt-3a) and small molecules (sodium butyrate and IDE 1) in different combinations...
October 16, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29044473/induced-pluripotent-stem-cells-from-ovarian-tissue
#15
Sophia Salas, Nicholas Ng, Behzad Gerami-Naini, Raymond M Anchan
Yamanaka and colleagues revolutionized stem cell biology and regenerative medicine by observing that somatic cells can be reprogrammed into pluripotent stem cells. Evidence indicates that induced pluripotent stem (iPS) cells retain epigenetic memories that bias their spontaneous differentiation into the originating somatic cell type, therefore epigenetic memory may be exploited to improve tissue specific regeneration. We recently showed that iPS cells reprogrammed from ovarian granulosa cells using mouse and human tissue overwhelmingly differentiate homotypically into ovarian steroidogenic and primordial germ cells...
October 18, 2017: Current Protocols in Human Genetics
https://www.readbyqxmd.com/read/29044469/co-differentiation-of-human-pluripotent-stem-cells-derived-cardiomyocytes-and-endothelial-cells-from-cardiac-mesoderm-provides-a-three-dimensional-model-of-cardiac-microtissue
#16
Elisa Giacomelli, Milena Bellin, Valeria V Orlova, Christine L Mummery
The formation of cardiac mesodermal subtypes is highly regulated in time and space during heart development. In vitro models based on human pluripotent stem cells (hPS cells) provide opportunities to study mechanisms underlying fate choices governing lineage specification from common cardiovascular progenitors in human embryos. The generation of cardiac endothelial cells in particular allows the creation of complex models of cardiovascular disorders in which either cardiomyocytes or endothelial cells are affected...
October 18, 2017: Current Protocols in Human Genetics
https://www.readbyqxmd.com/read/29044175/a-skeletal-muscle-model-of-infantile-onset-pompe-disease-with-patient-specific-ips-cells
#17
Takeshi Yoshida, Tomonari Awaya, Tatsuya Jonouchi, Ryo Kimura, Shigemi Kimura, Takumi Era, Toshio Heike, Hidetoshi Sakurai
Pompe disease is caused by an inborn defect of lysosomal acid α-glucosidase (GAA) and is characterized by lysosomal glycogen accumulation primarily in the skeletal muscle and heart. Patients with the severe type of the disease, infantile-onset Pompe disease (IOPD), show generalized muscle weakness and heart failure in early infancy. They cannot survive over two years. Enzyme replacement therapy with recombinant human GAA (rhGAA) improves the survival rate, but its effect on skeletal muscle is insufficient compared to other organs...
October 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29044152/a-machine-learning-assisted-label-free-non-invasive-approach-for-somatic-reprogramming-in-induced-pluripotent-stem-cell-colony-formation-detection-and-prediction
#18
Ke Fan, Sheng Zhang, Ying Zhang, Jun Lu, Mike Holcombe, Xiao Zhang
During cellular reprogramming, the mesenchymal-to-epithelial transition is accompanied by changes in morphology, which occur prior to iPSC colony formation. The current approach for detecting morphological changes associated with reprogramming purely relies on human experiences, which involve intensive amounts of upfront training, human error with limited quality control and batch-to-batch variations. Here, we report a time-lapse-based bright-field imaging analysis system that allows us to implement a label-free, non-invasive approach to measure morphological dynamics...
October 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29044119/the-wnt-target-sp5-negatively-regulates-wnt-transcriptional-programs-in-human-pluripotent-stem-cells
#19
Ian J Huggins, Tomas Bos, Olivia Gaylord, Christina Jessen, Brianna Lonquich, Angeline Puranen, Jenna Richter, Charlotte Rossdam, David Brafman, Terry Gaasterland, Karl Willert
The WNT/β-catenin signaling pathway is a prominent player in many developmental processes, including gastrulation, anterior-posterior axis specification, organ and tissue development, and homeostasis. Here, we use human pluripotent stem cells (hPSCs) to study the dynamics of the transcriptional response to exogenous activation of the WNT pathway. We describe a mechanism involving the WNT target gene SP5 that leads to termination of the transcriptional program initiated by WNT signaling. Integration of gene expression profiles of wild-type and SP5 mutant cells with genome-wide SP5 binding events reveals that SP5 acts to diminish expression of genes previously activated by the WNT pathway...
October 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/29044103/oct4-impedes-cell-fate-redirection-by-the-melanocyte-lineage-master-regulator-mitf-in-mouse-escs
#20
Danna Sheinboim, Itay Maza, Iris Dror, Shivang Parikh, Vladislav Krupalnik, Rachel E Bell, Asaf Zviran, Yusuke Suita, Ofir Hakim, Yael Mandel-Gutfreund, Mehdi Khaled, Jacob H Hanna, Carmit Levy
Ectopic expression of lineage master regulators induces transdifferentiation. Whether cell fate transitions can be induced during various developmental stages has not been systemically examined. Here we discover that amongst different developmental stages, mouse embryonic stem cells (mESCs) are resistant to cell fate conversion induced by the melanocyte lineage master regulator MITF. By generating a transgenic system we exhibit that in mESCs, the pluripotency master regulator Oct4, counteracts pro-differentiation induced by Mitf by physical interference with MITF transcriptional activity...
October 18, 2017: Nature Communications
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