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Cell Stem Cell

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https://www.readbyqxmd.com/read/29337182/human-pancreatic-tumor-organoids-reveal-loss-of-stem-cell-niche-factor-dependence-during-disease-progression
#1
Takashi Seino, Shintaro Kawasaki, Mariko Shimokawa, Hiroki Tamagawa, Kohta Toshimitsu, Masayuki Fujii, Yuki Ohta, Mami Matano, Kosaku Nanki, Kenta Kawasaki, Sirirat Takahashi, Shinya Sugimoto, Eisuke Iwasaki, Junichi Takagi, Takao Itoi, Minoru Kitago, Yuko Kitagawa, Takanori Kanai, Toshiro Sato
Despite recent efforts to dissect the inter-tumor heterogeneity of pancreatic ductal adenocarcinoma (PDAC) by determining prognosis-predictive gene expression signatures for specific subtypes, their functional differences remain elusive. Here, we established a pancreatic tumor organoid library encompassing 39 patient-derived PDACs and identified 3 functional subtypes based on their stem cell niche factor dependencies on Wnt and R-spondin. A Wnt-non-producing subtype required Wnt from cancer-associated fibroblasts, whereas a Wnt-producing subtype autonomously secreted Wnt ligands and an R-spondin-independent subtype grew in the absence of Wnt and R-spondin...
January 10, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29337183/temporal-layering-of-signaling-effectors-drives-chromatin-remodeling-during-hair-follicle-stem-cell-lineage-progression
#2
Rene C Adam, Hanseul Yang, Yejing Ge, Wen-Hui Lien, Ping Wang, Yilin Zhao, Lisa Polak, John Levorse, Sanjeethan C Baksh, Deyou Zheng, Elaine Fuchs
Tissue regeneration relies on resident stem cells (SCs), whose activity and lineage choices are influenced by the microenvironment. Exploiting the synchronized, cyclical bouts of tissue regeneration in hair follicles (HFs), we investigate how microenvironment dynamics shape the emergence of stem cell lineages. Employing epigenetic and ChIP-seq profiling, we uncover how signal-dependent transcription factors couple spatiotemporal cues to chromatin dynamics, thereby choreographing stem cell lineages. Using enhancer-driven reporters, mutagenesis, and genetics, we show that simultaneous BMP-inhibitory and WNT signals set the stage for lineage choices by establishing chromatin platforms permissive for diversification...
January 9, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29337181/a-non-canonical-bcor-prc1-1-complex-represses-differentiation-programs-in-human-escs
#3
Zheng Wang, Micah D Gearhart, Yu-Wei Lee, Ishan Kumar, Bulat Ramazanov, Yan Zhang, Charles Hernandez, Alice Y Lu, Nils Neuenkirchen, Jingjing Deng, Jiaqi Jin, Yuval Kluger, Thomas A Neubert, Vivian J Bardwell, Natalia B Ivanova
Polycomb group proteins regulate self-renewal and differentiation in many stem cell systems. When assembled into two canonical complexes, PRC1 and PRC2, they sequentially deposit H3K27me3 and H2AK119ub histone marks and establish repressive chromatin, referred to as Polycomb domains. Non-canonical PRC1 complexes retain RING1/RNF2 E3-ubiquitin ligases but have unique sets of accessory subunits. How these non-canonical complexes recognize and regulate their gene targets remains poorly understood. Here, we show that the BCL6 co-repressor (BCOR), a member of the PRC1...
January 8, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29290616/reconstruction-of-the-human-colon-epithelium-in%C3%A2-vivo
#4
Shinya Sugimoto, Yuki Ohta, Masayuki Fujii, Mami Matano, Mariko Shimokawa, Kosaku Nanki, Shoichi Date, Shingo Nishikori, Yoshihiro Nakazato, Tetsuya Nakamura, Takanori Kanai, Toshiro Sato
Genetic lineage tracing has revealed that Lgr5+ murine colon stem cells (CoSCs) rapidly proliferate at the crypt bottom. However, the spatiotemporal dynamics of human CoSCs in vivo have remained experimentally intractable. Here we established an orthotopic xenograft system for normal human colon organoids, enabling stable reconstruction of the human colon epithelium in vivo. Xenografted organoids were prone to displacement by the remaining murine crypts, and this could be overcome by complete removal of the mouse epithelium...
December 21, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29276142/radial-glial-fibers-promote-neuronal-migration-and-functional-recovery-after-neonatal-brain-injury
#5
Hideo Jinnou, Masato Sawada, Koya Kawase, Naoko Kaneko, Vicente Herranz-Pérez, Takuya Miyamoto, Takumi Kawaue, Takaki Miyata, Yasuhiko Tabata, Toshihiro Akaike, José Manuel García-Verdugo, Itsuki Ajioka, Shinji Saitoh, Kazunobu Sawamoto
Radial glia (RG) are embryonic neural stem cells (NSCs) that produce neuroblasts and provide fibers that act as a scaffold for neuroblast migration during embryonic development. Although they normally disappear soon after birth, here we found that RG fibers can persist in injured neonatal mouse brains and act as a scaffold for postnatal ventricular-subventricular zone (V-SVZ)-derived neuroblasts that migrate to the lesion site. This injury-induced maintenance of RG fibers has a limited time window during post-natal development and promotes directional saltatory movement of neuroblasts via N-cadherin-mediated cell-cell contacts that promote RhoA activation...
December 14, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29290617/mettl14-inhibits-hematopoietic-stem-progenitor-differentiation-and-promotes-leukemogenesis-via-mrna-m6a-modification
#6
Hengyou Weng, Huilin Huang, Huizhe Wu, Xi Qin, Boxuan Simen Zhao, Lei Dong, Hailing Shi, Jennifer Skibbe, Chao Shen, Chao Hu, Yue Sheng, Yungui Wang, Mark Wunderlich, Bin Zhang, Louis C Dore, Rui Su, Xiaolan Deng, Kyle Ferchen, Chenying Li, Miao Sun, Zhike Lu, Xi Jiang, Guido Marcucci, James C Mulloy, Jianhua Yang, Zhijian Qian, Minjie Wei, Chuan He, Jianjun Chen
N6-methyladenosine (m6A), the most prevalent internal modification in eukaryotic messenger RNAs (mRNAs), plays critical roles in many bioprocesses. However, its functions in normal and malignant hematopoiesis remain elusive. Here, we report that METTL14, a key component of the m6A methyltransferase complex, is highly expressed in normal hematopoietic stem/progenitor cells (HSPCs) and acute myeloid leukemia (AML) cells carrying t(11q23), t(15;17), or t(8;21) and is downregulated during myeloid differentiation...
December 8, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29276143/inhibition-of-endosteal-vascular-niche-remodeling-rescues-hematopoietic-stem-cell-loss-in-aml
#7
Delfim Duarte, Edwin D Hawkins, Olufolake Akinduro, Heather Ang, Katia De Filippo, Isabella Y Kong, Myriam Haltalli, Nicola Ruivo, Lenny Straszkowski, Stephin J Vervoort, Catriona McLean, Tom S Weber, Reema Khorshed, Chiara Pirillo, Andrew Wei, Saravana K Ramasamy, Anjali P Kusumbe, Ken Duffy, Ralf H Adams, Louise E Purton, Leo M Carlin, Cristina Lo Celso
Bone marrow vascular niches sustain hematopoietic stem cells (HSCs) and are drastically remodeled in leukemia to support pathological functions. Acute myeloid leukemia (AML) cells produce angiogenic factors, which likely contribute to this remodeling, but anti-angiogenic therapies do not improve AML patient outcomes. Using intravital microscopy, we found that AML progression leads to differential remodeling of vasculature in central and endosteal bone marrow regions. Endosteal AML cells produce pro-inflammatory and anti-angiogenic cytokines and gradually degrade endosteal endothelium, stromal cells, and osteoblastic cells, whereas central marrow remains vascularized and splenic vascular niches expand...
December 6, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29249463/derivation-of-human-trophoblast-stem-cells
#8
Hiroaki Okae, Hidehiro Toh, Tetsuya Sato, Hitoshi Hiura, Sota Takahashi, Kenjiro Shirane, Yuka Kabayama, Mikita Suyama, Hiroyuki Sasaki, Takahiro Arima
Trophoblast cells play an essential role in the interactions between the fetus and mother. Mouse trophoblast stem (TS) cells have been derived and used as the best in vitro model for molecular and functional analysis of mouse trophoblast lineages, but attempts to derive human TS cells have so far been unsuccessful. Here we show that activation of Wingless/Integrated (Wnt) and EGF and inhibition of TGF-β, histone deacetylase (HDAC), and Rho-associated protein kinase (ROCK) enable long-term culture of human villous cytotrophoblast (CT) cells...
November 30, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29249464/yap-taz-dependent-reprogramming-of-colonic-epithelium-links-ecm-remodeling-to-tissue-regeneration
#9
Shiro Yui, Luca Azzolin, Martti Maimets, Marianne Terndrup Pedersen, Robert P Fordham, Stine L Hansen, Hjalte L Larsen, Jordi Guiu, Mariana R P Alves, Carsten F Rundsten, Jens V Johansen, Yuan Li, Chris D Madsen, Tetsuya Nakamura, Mamoru Watanabe, Ole H Nielsen, Pawel J Schweiger, Stefano Piccolo, Kim B Jensen
Tissue regeneration requires dynamic cellular adaptation to the wound environment. It is currently unclear how this is orchestrated at the cellular level and how cell fate is affected by severe tissue damage. Here we dissect cell fate transitions during colonic regeneration in a mouse dextran sulfate sodium (DSS) colitis model, and we demonstrate that the epithelium is transiently reprogrammed into a primitive state. This is characterized by de novo expression of fetal markers as well as suppression of markers for adult stem and differentiated cells...
November 28, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29198941/hypoxic-induction-of-vasorin-regulates-notch1-turnover-to-maintain-glioma-stem-like-cells
#10
Jianghong Man, Xingjiang Yu, Haidong Huang, Wenchao Zhou, Chaomei Xiang, Haohao Huang, Lucio Miele, Zhenggang Liu, Gurkan Bebek, Shideng Bao, Jennifer S Yu
Tumor hypoxia is associated with poor patient survival and is a characteristic of glioblastoma. Notch signaling is implicated in maintaining glioma stem-like cells (GSCs) within the hypoxic niche, although the molecular mechanisms linking hypoxia to Notch activation have not been clearly delineated. Here we show that Vasorin is a critical link between hypoxia and Notch signaling in GSCs. Vasorin is preferentially induced in GSCs by a HIF1α/STAT3 co-activator complex and stabilizes Notch1 protein at the cell membrane...
November 23, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29174332/injury-induces-endogenous-reprogramming-and-dedifferentiation-of-neuronal-progenitors-to-multipotency
#11
Brian Lin, Julie H Coleman, Jesse N Peterson, Matthew J Zunitch, Woochan Jang, Daniel B Herrick, James E Schwob
Adult neurogenesis in the olfactory epithelium is often depicted as a unidirectional pathway during homeostasis and repair. We challenge the unidirectionality of this model by showing that epithelial injury unlocks the potential for Ascl1+ progenitors and Neurog1+ specified neuronal precursors to dedifferentiate into multipotent stem/progenitor cells that contribute significantly to tissue regeneration in the murine olfactory epithelium (OE). We characterize these dedifferentiating cells using several lineage-tracing strains and single-cell mRNA-seq, and we show that Sox2 is required for initiating dedifferentiation and that inhibition of Ezh2 promotes multipotent progenitor expansion...
November 20, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29198942/dye-independent-methods-reveal-elevated-mitochondrial-mass-in-hematopoietic-stem-cells
#12
Mariana Justino de Almeida, Larry L Luchsinger, David J Corrigan, Linda J Williams, Hans-Willem Snoeck
Hematopoietic stem cells (HSCs) produce most cellular energy through glycolysis rather than through mitochondrial respiration. Consistent with this notion, mitochondrial mass has been reported to be low in HSCs. However, we found that staining with MitoTracker Green, a commonly used dye to measure mitochondrial content, leads to artefactually low fluorescence specifically in HSCs because of dye efflux. Using mtDNA quantification, enumeration of mitochondrial nucleoids, and fluorescence intensity of a genetically encoded mitochondrial reporter, we unequivocally show here that HSCs and multipotential progenitors (MPPs) have higher mitochondrial mass than lineage-committed progenitors and mature cells...
November 18, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29198940/bone-marrow-myeloid-cells-regulate-myeloid-biased-hematopoietic-stem-cells-via-a-histamine-dependent-feedback-loop
#13
Xiaowei Chen, Huan Deng, Michael J Churchill, Larry L Luchsinger, Xing Du, Timothy H Chu, Richard A Friedman, Moritz Middelhoff, Hongxu Ding, Yagnesh H Tailor, Alexander L E Wang, Haibo Liu, Zhengchuan Niu, Hongshan Wang, Zhenyu Jiang, Simon Renders, Siu-Hong Ho, Spandan V Shah, Pavel Tishchenko, Wenju Chang, Theresa C Swayne, Laura Munteanu, Andrea Califano, Ryota Takahashi, Karan K Nagar, Bernhard W Renz, Daniel L Worthley, C Benedikt Westphalen, Yoku Hayakawa, Samuel Asfaha, Florence Borot, Chyuan-Sheng Lin, Hans-Willem Snoeck, Siddhartha Mukherjee, Timothy C Wang
Myeloid-biased hematopoietic stem cells (MB-HSCs) play critical roles in recovery from injury, but little is known about how they are regulated within the bone marrow niche. Here we describe an auto-/paracrine physiologic circuit that controls quiescence of MB-HSCs and hematopoietic progenitors marked by histidine decarboxylase (Hdc). Committed Hdc+ myeloid cells lie in close anatomical proximity to MB-HSCs and produce histamine, which activates the H2 receptor on MB-HSCs to promote their quiescence and self-renewal...
November 17, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29174333/injury-activates-transient-olfactory-stem-cell-states-with-diverse-lineage-capacities
#14
Levi Gadye, Diya Das, Michael A Sanchez, Kelly Street, Ariane Baudhuin, Allon Wagner, Michael B Cole, Yoon Gi Choi, Nir Yosef, Elizabeth Purdom, Sandrine Dudoit, Davide Risso, John Ngai, Russell B Fletcher
Tissue homeostasis and regeneration are mediated by programs of adult stem cell renewal and differentiation. However, the mechanisms that regulate stem cell fates under such widely varying conditions are not fully understood. Using single-cell techniques, we assessed the transcriptional changes associated with stem cell self-renewal and differentiation and followed the maturation of stem cell-derived clones using sparse lineage tracing in the regenerating mouse olfactory epithelium. Following injury, quiescent olfactory stem cells rapidly shift to activated, transient states unique to regeneration and tailored to meet the demands of injury-induced repair, including barrier formation and proliferation...
November 17, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29174331/constitutively-active-smad2-3-are-broad-scope-potentiators-of-transcription-factor-mediated-cellular-reprogramming
#15
Tyson Ruetz, Ulrich Pfisterer, Bruno Di Stefano, James Ashmore, Meryam Beniazza, Tian V Tian, Daniel F Kaemena, Luca Tosti, Wenfang Tan, Jonathan R Manning, Eleni Chantzoura, Daniella Rylander Ottosson, Samuel Collombet, Anna Johnsson, Erez Cohen, Kosuke Yusa, Sten Linnarsson, Thomas Graf, Malin Parmar, Keisuke Kaji
Reprogramming of cellular identity using exogenous expression of transcription factors (TFs) is a powerful and exciting tool for tissue engineering, disease modeling, and regenerative medicine. However, generation of desired cell types using this approach is often plagued by inefficiency, slow conversion, and an inability to produce mature functional cells. Here, we show that expression of constitutively active SMAD2/3 significantly improves the efficiency of induced pluripotent stem cell (iPSC) generation by the Yamanaka factors...
November 13, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29129523/higher-order-kidney-organogenesis-from-pluripotent-stem-cells
#16
Atsuhiro Taguchi, Ryuichi Nishinakamura
Organogenesis generates higher-order structures containing functional subunits, connective components, and progenitor niches. Despite recent advances in organoid-based modeling of tissue development, recapitulating these complex configurations from pluripotent stem cells (PSCs) has remained challenging. In this study, we report assembly of kidney organoids that recapitulate embryonic branching morphogenesis. By studying the distinct origins and developmental processes of the ureteric bud, which contains epithelial kidney progenitors that undergo branching morphogenesis and thereby plays a central role in orchestrating organ geometry, and neighboring mesenchymal nephron progenitors, we established a protocol for differential induction of each lineage from mouse and human PSCs...
November 4, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29304344/endogenous-reprogramming-of-alpha-cells-into-beta-cells-induced-by-viral-gene-therapy-reverses-autoimmune-diabetes
#17
Xiangwei Xiao, Ping Guo, Chiyo Shiota, Ting Zhang, Gina M Coudriet, Shane Fischbach, Krishna Prasadan, Joseph Fusco, Sabarinathan Ramachandran, Piotr Witkowski, Jon D Piganelli, George K Gittes
Successful strategies for treating type 1 diabetes need to restore the function of pancreatic beta cells that are destroyed by the immune system and overcome further destruction of insulin-producing cells. Here, we infused adeno-associated virus carrying Pdx1 and MafA expression cassettes through the pancreatic duct to reprogram alpha cells into functional beta cells and normalized blood glucose in both beta cell-toxin-induced diabetic mice and in autoimmune non-obese diabetic (NOD) mice. The euglycemia in toxin-induced diabetic mice and new insulin+ cells persisted in the autoimmune NOD mice for 4 months prior to reestablishment of autoimmune diabetes...
January 4, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29304343/think-about-the-environment-cellular-reprogramming-by-the-extracellular-matrix
#18
David J Huels, Jan Paul Medema
In this issue of Cell Stem Cell, Yui et al. (2018) show how tissue regeneration is driven by changes in the microenvironment. During intestinal regeneration, the epithelium is reprogrammed into a fetal state by an altered extracellular matrix (ECM), which is dependent on YAP/TAZ activation.
January 4, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29304342/chewing-through-roots-how-leukemia-invades-and-disrupts-the-bone-marrow-microenvironment
#19
Owen J Tamplin
The bone marrow (BM) niche is a complex microenvironment that supports healthy hematopoietic stem cells (HSCs) throughout life. In this issue of Cell Stem Cell, Duarte et al. (2018) reveal the spatio-temporal progress of leukemic cells as they invade and occupy the niche, ultimately outcompeting native HSCs.
January 4, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29304341/a-coated-sponge-toward-neonatal-brain-repair
#20
Orly Reiner, Tamar Sapir
In this issue of Cell Stem Cell, Jinnou et al. (2018) identify a limited time window wherein neonatal brain injuries may be treated through neuroblast migration toward the injury site on radial glial fibers. Implanting a sponge coated with an adhesive factor in the injured neonatal brain supports the migration of neuroblasts and improves functional recovery.
January 4, 2018: Cell Stem Cell
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