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Stem Cell Reports

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https://www.readbyqxmd.com/read/27916538/myofibroblasts-derived-from-hepatic-progenitor-cells-create-the-tumor-microenvironment
#1
Sayaka Sekiya, Shizuka Miura, Kanae Matsuda-Ito, Atsushi Suzuki
Hepatic progenitor cells (HPCs) appear in response to several types of chronic injury in the human and rodent liver that often develop into liver fibrosis, cirrhosis, and primary liver cancers. However, the contribution of HPCs to the pathogenesis and progression of such liver diseases remains controversial. HPCs are generally defined as cells that can differentiate into hepatocytes and cholangiocytes. In this study, however, we found that HPCs isolated from the chronically injured liver can also give rise to myofibroblasts as a third type of descendant...
November 26, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27916539/inhibiting-the-sumo-pathway-represses-the-cancer-stem-cell-population-in-breast-and-colorectal-carcinomas
#2
Maria V Bogachek, Jung M Park, James P De Andrade, Allison W Lorenzen, Mikhail V Kulak, Jeffrey R White, Vivian W Gu, Vincent T Wu, Ronald J Weigel
Many solid cancers have an expanded CD44(+/hi)/CD24(-/low) cancer stem cell (CSC) population, which are relatively chemoresistant and drive recurrence and metastasis. Achieving a more durable response requires the development of therapies that specifically target CSCs. Recent evidence indicated that inhibiting the SUMO pathway repressed tumor growth and invasiveness, although the mechanism has yet to be clarified. Here, we demonstrate that inhibition of the SUMO pathway repressed MMP14 and CD44 with a concomitant reduction in cell invasiveness and functional loss of CSCs in basal breast cancer...
November 24, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27866875/p53-and-p73-regulate-apoptosis-but-not-cell-cycle-progression-in-mouse-embryonic-stem-cells-upon-dna-damage-and-differentiation
#3
Hanbing He, Cheng Wang, Qian Dai, Fengtian Li, Johann Bergholz, Zhonghan Li, Qintong Li, Zhi-Xiong Xiao
Embryonic stem cells (ESCs) are fast proliferating cells capable of differentiating into all somatic cell types. In somatic cells, it is well documented that p53 is rapidly activated upon DNA damage to arrest the cell cycle and induce apoptosis. In mouse ESCs, p53 can also be functionally activated, but the precise biological consequences are not well characterized. Here, we demonstrated that doxorubicin treatment initially led to cell-cycle arrest at G2/M in ESCs, followed by the occurrence of massive apoptosis...
November 16, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27866876/prdm14-drives-oct3-4-recruitment-via-active-demethylation-in-the-transition-from-primed-to-naive-pluripotency
#4
Naoki Okashita, Yoshiaki Suwa, Osamu Nishimura, Nao Sakashita, Mitsutaka Kadota, Go Nagamatsu, Masanori Kawaguchi, Hiroki Kashida, Ayaka Nakajima, Makoto Tachibana, Yoshiyuki Seki
Primordial germ cells (PGCs) are specified from epiblast cells in mice. Genes associated with naive pluripotency are repressed in the transition from inner cell mass to epiblast cells, followed by upregulation after PGC specification. However, the molecular mechanisms underlying the reactivation of pluripotency genes are poorly characterized. Here, we exploited the in vitro differentiation of epiblast-like cells (EpiLCs) from embryonic stem cells (ESCs) to elucidate the molecular and epigenetic functions of PR domain-containing 14 (PRDM14)...
November 14, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27866874/par1-scaffolds-tgf%C3%AE-rii-to-downregulate-tgf-%C3%AE-signaling-and-activate-esc-differentiation-to-endothelial-cells
#5
Haixia Gong, Shejuan An, Antonia Sassmann, Menglin Liu, Victoria Mastej, Manish Mittal, Wei Zhang, Zhigang Hong, Stefan Offermanns, Jalees Rehman, Asrar B Malik
We studied the function of the G-protein-coupled receptor PAR1 in mediating the differentiation of mouse embryonic stem cells (mESCs) to endothelial cells (ECs) that are capable of inducing neovascularization. We observed that either deletion or activation of PAR1 suppressed mouse embryonic stem cell (mESC) differentiation to ECs and neovascularization in mice. This was mediated by induction of TGFβRII/TGFβRI interaction, forming an active complex, which in turn induced SMAD2 phosphorylation. Inhibition of TGF-β signaling in PAR1-deficient mESCs restored the EC differentiation potential of mESCs...
November 14, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27840045/cgg-repeat-induced-fmr1-silencing-depends-on-the-expansion-size-in-human-ipscs-and-neurons-carrying-unmethylated-full-mutations
#6
Urszula Brykczynska, Eline Pecho-Vrieseling, Anke Thiemeyer, Jessica Klein, Isabelle Fruh, Thierry Doll, Carole Manneville, Sascha Fuchs, Mariavittoria Iazeolla, Martin Beibel, Guglielmo Roma, Ulrike Naumann, Nicholas Kelley, Edward J Oakeley, Matthias Mueller, Baltazar Gomez-Mancilla, Marc Bühler, Elisabetta Tabolacci, Pietro Chiurazzi, Giovanni Neri, Tewis Bouwmeester, Francesco Paolo Di Giorgio, Barna D Fodor
In fragile X syndrome (FXS), CGG repeat expansion greater than 200 triplets is believed to trigger FMR1 gene silencing and disease etiology. However, FXS siblings have been identified with more than 200 CGGs, termed unmethylated full mutation (UFM) carriers, without gene silencing and disease symptoms. Here, we show that hypomethylation of the FMR1 promoter is maintained in induced pluripotent stem cells (iPSCs) derived from two UFM individuals. However, a subset of iPSC clones with large CGG expansions carries silenced FMR1...
November 8, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27840044/in%C3%A2-vitro-models-of-gjb2-related-hearing-loss-recapitulate-ca-2-transients-via-a-gap-junction-characteristic-of-developing-cochlea
#7
Ichiro Fukunaga, Ayumi Fujimoto, Kaori Hatakeyama, Toru Aoki, Atena Nishikawa, Tetsuo Noda, Osamu Minowa, Nagomi Kurebayashi, Katsuhisa Ikeda, Kazusaku Kamiya
Mutation of the Gap Junction Beta 2 gene (GJB2) encoding connexin 26 (CX26) is the most frequent cause of hereditary deafness worldwide and accounts for up to 50% of non-syndromic sensorineural hearing loss cases in some populations. Therefore, cochlear CX26-gap junction plaque (GJP)-forming cells such as cochlear supporting cells are thought to be the most important therapeutic target for the treatment of hereditary deafness. The differentiation of pluripotent stem cells into cochlear CX26-GJP-forming cells has not been reported...
November 8, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27818139/cited2-cooperates-with-isl1-and-promotes-cardiac-differentiation-of-mouse-embryonic-stem-cells
#8
Ivette Pacheco-Leyva, Ana Catarina Matias, Daniel V Oliveira, João M A Santos, Rita Nascimento, Eduarda Guerreiro, Anna C Michell, Annebel M van De Vrugt, Gisela Machado-Oliveira, Guilherme Ferreira, Ibrahim Domian, José Bragança
The transcriptional regulator CITED2 is essential for heart development. Here, we investigated the role of CITED2 in the specification of cardiac cell fate from mouse embryonic stem cells (ESC). The overexpression of CITED2 in undifferentiated ESC was sufficient to promote cardiac cell emergence upon differentiation. Conversely, the depletion of Cited2 at the onset of differentiation resulted in a decline of ESC ability to generate cardiac cells. Moreover, loss of Cited2 expression impairs the expression of early mesoderm markers and cardiogenic transcription factors (Isl1, Gata4, Tbx5)...
October 31, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27829140/detecting-genetic-mosaicism-in-cultures-of-human-pluripotent-stem-cells
#9
Duncan Baker, Adam J Hirst, Paul J Gokhale, Miguel A Juarez, Steve Williams, Mark Wheeler, Kerry Bean, Thomas F Allison, Harry D Moore, Peter W Andrews, Ivana Barbaric
Genetic changes in human pluripotent stem cells (hPSCs) gained during culture can confound experimental results and potentially jeopardize the outcome of clinical therapies. Particularly common changes in hPSCs are trisomies of chromosomes 1, 12, 17, and 20. Thus, hPSCs should be regularly screened for such aberrations. Although a number of methods are used to assess hPSC genotypes, there has been no systematic evaluation of the sensitivity of the commonly used techniques in detecting low-level mosaicism in hPSC cultures...
November 8, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27773702/transcriptional-and-chromatin-dynamics-of-muscle-regeneration-after-severe-trauma
#10
Carlos A Aguilar, Ramona Pop, Anna Shcherbina, Alain Watts, Ronald W Matheny, Davide Cacchiarelli, Woojin M Han, Eunjung Shin, Shadi A Nakhai, Young C Jang, Christopher T Carrigan, Casey A Gifford, Melissa A Kottke, Marcella Cesana, Jackson Lee, Maria L Urso, Alexander Meissner
Following injury, adult skeletal muscle undergoes a well-coordinated sequence of molecular and physiological events to promote repair and regeneration. However, a thorough understanding of the in vivo epigenomic and transcriptional mechanisms that control these reparative events is lacking. To address this, we monitored the in vivo dynamics of three histone modifications and coding and noncoding RNA expression throughout the regenerative process in a mouse model of traumatic muscle injury. We first illustrate how both coding and noncoding RNAs in tissues and sorted satellite cells are modified and regulated during various stages after trauma...
November 8, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27773701/rare-sox2-airway-progenitor-cells-generate-krt5-cells-that-repopulate-damaged-alveolar-parenchyma-following-influenza-virus-infection
#11
Samriddha Ray, Norika Chiba, Changfu Yao, Xiangrong Guan, Alicia M McConnell, Brian Brockway, Loretta Que, Jonathan L McQualter, Barry R Stripp
Recent studies have implicated keratin 5 (KRT5)(+) cells in repopulation of damaged lung tissue following severe H1N1 influenza virus infection. However, the origins of the cells repopulating the injured alveolar region remain controversial. We sought to determine the cellular dynamics of lung repair following influenza infection and define whether nascent KRT5(+) cells repopulating alveolar epithelium were derived from pre-existing alveolar or airway progenitor cells. We found that the wound-healing response begins with proliferation of SOX2(+) SCGB1A1(-) KRT5(-) progenitor cells in airways...
November 8, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27773700/marked-differences-in-c9orf72-methylation-status-and-isoform-expression-between-c9-als-human-embryonic-and-induced-pluripotent-stem-cells
#12
Yaara Cohen-Hadad, Gheona Altarescu, Talia Eldar-Geva, Ephrat Levi-Lahad, Ming Zhang, Ekaterina Rogaeva, Marc Gotkine, Osnat Bartok, Reut Ashwal-Fluss, Sebastian Kadener, Silvina Epsztejn-Litman, Rachel Eiges
We established two human embryonic stem cell (hESC) lines with a GGGGCC expansion in the C9orf72 gene (C9), and compared them with haploidentical and unrelated C9 induced pluripotent stem cells (iPSCs). We found a marked difference in C9 methylation between the cells. hESCs and parental fibroblasts are entirely unmethylated while the iPSCs are hypermethylated. In addition, we show that the expansion alters promoter usage and interferes with the proper splicing of intron 1, eventually leading to the accumulation of repeat-containing mRNA following neural differentiation...
November 8, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27746116/cnot3-dependent-mrna-deadenylation-safeguards-the-pluripotent-state
#13
Xiaofeng Zheng, Pengyi Yang, Brad Lackford, Brian D Bennett, Li Wang, Hui Li, Yu Wang, Yiliang Miao, Julie F Foley, David C Fargo, Ying Jin, Carmen J Williams, Raja Jothi, Guang Hu
Poly(A) tail length and mRNA deadenylation play important roles in gene regulation. However, how they regulate embryonic development and pluripotent cell fate is not fully understood. Here we present evidence that CNOT3-dependent mRNA deadenylation governs the pluripotent state. We show that CNOT3, a component of the Ccr4-Not deadenylase complex, is required for mouse epiblast maintenance. It is highly expressed in blastocysts and its deletion leads to peri-implantation lethality. The epiblast cells in Cnot3 deletion embryos are quickly lost during diapause and fail to outgrow in culture...
November 8, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27746115/generation-and-analysis-of-gata2-w-egfp-human-escs-reveal-itgb3-cd61-as-a-reliable-marker-for-defining-hemogenic-endothelial-cells-during-hematopoiesis
#14
Ke Huang, Jiao Gao, Juan Du, Ning Ma, Yanling Zhu, Pengfei Wu, Tian Zhang, Wenqian Wang, Yuhang Li, Qianyu Chen, Andrew Paul Hutchins, Zhongzhou Yang, Yi Zheng, Jian Zhang, Yongli Shan, Xuejia Li, Baojian Liao, Jiajun Liu, Jinyong Wang, Bing Liu, Guangjin Pan
The transition from hemogenic endothelial cells (HECs) to hematopoietic stem/progenitor cells (HS/PCs), or endothelial to hematopoietic transition (EHT), is a critical step during hematopoiesis. However, little is known about the molecular determinants of HECs due to the challenge in defining HECs. We report here the generation of GATA2(w/eGFP) reporter in human embryonic stem cells (hESCs) to mark cells expressing GATA2, a critical gene for EHT. We show that during differentiation, functional HECs are almost exclusively GATA2/eGFP(+)...
November 8, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27720906/transient-runx1-expression-during-early-mesendodermal-differentiation-of%C3%A2-hescs-promotes-epithelial-to-mesenchymal-transition-through-tgfb2-signaling
#15
Jennifer J VanOudenhove, Ricardo Medina, Prachi N Ghule, Jane B Lian, Janet L Stein, Sayyed K Zaidi, Gary S Stein
The transition of human embryonic stem cells (hESCs) from pluripotency to lineage commitment is not fully understood, and a role for phenotypic transcription factors in the initial stages of hESC differentiation remains to be explored. From a screen of candidate factors, we found that RUNX1 is selectively and transiently upregulated early in hESC differentiation to mesendodermal lineages. Transcriptome profiling and functional analyses upon RUNX1 depletion established a role for RUNX1 in promoting cell motility...
November 8, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27720905/a-dynamic-wnt-%C3%AE-catenin-signaling-environment-leads-to-wnt-independent-and-wnt-dependent-proliferation-of-embryonic-intestinal-progenitor-cells
#16
Alana M Chin, Yu-Hwai Tsai, Stacy R Finkbeiner, Melinda S Nagy, Emily M Walker, Nicole J Ethen, Bart O Williams, Michele A Battle, Jason R Spence
Much of our understanding about how intestinal stem and progenitor cells are regulated comes from studying the late fetal stages of development and the adult intestine. In this light, little is known about intestine development prior to the formation of stereotypical villus structures with columnar epithelium, a stage when the epithelium is pseudostratified and appears to be a relatively uniform population of progenitor cells with high proliferative capacity. Here, we investigated a role for WNT/β-CATENIN signaling during the pseudostratified stages of development (E13...
November 8, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27720904/endogenous-dna-damage-leads-to-p53-independent-deficits-in-replicative-fitness-in-fetal-murine-fancd2-hematopoietic-stem-and-progenitor-cells
#17
Young Me Yoon, Kelsie J Storm, Ashley N Kamimae-Lanning, Natalya A Goloviznina, Peter Kurre
Our mechanistic understanding of Fanconi anemia (FA) pathway function in hematopoietic stem and progenitor cells (HSPCs) owes much to their role in experimentally induced DNA crosslink lesion repair. In bone marrow HSPCs, unresolved stress confers p53-dependent apoptosis and progressive cell attrition. The role of FA proteins during hematopoietic development, in the face of physiological replicative demand, remains elusive. Here, we reveal a fetal HSPC pool in Fancd2(-/-) mice with compromised clonogenicity and repopulation...
November 8, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27720903/early-development-of-definitive-erythroblasts-from-human-pluripotent-stem-cells-defined-by-expression-of-glycophorin-a-cd235a-cd34-and-cd36
#18
Bin Mao, Shu Huang, Xulin Lu, Wencui Sun, Ya Zhou, Xu Pan, Jinfeng Yu, Mowen Lai, Bo Chen, Qiongxiu Zhou, Song Mao, Guohui Bian, Jiaxi Zhou, Tatsutoshi Nakahata, Feng Ma
The development of human erythroid cells has been mostly examined in models of adult hematopoiesis, while their early derivation during embryonic and fetal stages is largely unknown. We observed the development and maturation of erythroblasts derived from human pluripotent stem cells (hPSCs) by an efficient co-culture system. These hPSC-derived early erythroblasts initially showed definitive characteristics with a glycophorin A(+) (GPA(+)) CD34(low)CD36(-) phenotype and were distinct from adult CD34(+) cell-derived ones...
November 8, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27720902/targeted-differentiation-of-regional-ventral-neuroprogenitors-and-related-neuronal-subtypes-from-human-pluripotent-stem-cells
#19
Liankai Chi, Beibei Fan, Kunshan Zhang, Yanhua Du, Zhongliang Liu, Yujiang Fang, Zhenyu Chen, Xudong Ren, Xiangjie Xu, Cizhong Jiang, Siguang Li, Lin Ma, Liang Gao, Ling Liu, Xiaoqing Zhang
Embryoid body (EB) formation and adherent culture (AD) paradigms are equivalently thought to be applicable for neural specification of human pluripotent stem cells. Here, we report that sonic hedgehog-induced ventral neuroprogenitors under EB conditions are fated to medial ganglionic eminence (MGE), while the AD cells mostly adopt a floor-plate (FP) fate. The EB-MGE later on differentiates into GABA and cholinergic neurons, while the AD-FP favors dopaminergic neuron specification. Distinct developmental, metabolic, and adhesion traits in AD and EB cells may potentially account for their differential patterning potency...
November 8, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27693427/esc-derived-bdnf-overexpressing-neural-progenitors-differentially-promote-recovery-in-huntington-s-disease-models-by-enhanced-striatal-differentiation
#20
Tina Zimmermann, Floortje Remmers, Beat Lutz, Julia Leschik
Huntington's disease (HD) is characterized by fatal motoric failures induced by loss of striatal medium spiny neurons. Neuronal cell death has been linked to impaired expression and axonal transport of the neurotrophin BDNF (brain-derived neurotrophic factor). By transplanting embryonic stem cell-derived neural progenitors overexpressing BDNF, we combined cell replacement and BDNF supply as a potential HD therapy approach. Transplantation of purified neural progenitors was analyzed in a quinolinic acid (QA) chemical and two genetic HD mouse models (R6/2 and N171-82Q) on the basis of distinct behavioral parameters, including CatWalk gait analysis...
October 11, 2016: Stem Cell Reports
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