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Cell Stem Cell

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https://www.readbyqxmd.com/read/28343983/comprehensive-cell-surface-protein-profiling-identifies-specific-markers-of-human-naive-and-primed-pluripotent-states
#1
Amanda J Collier, Sarita P Panula, John Paul Schell, Peter Chovanec, Alvaro Plaza Reyes, Sophie Petropoulos, Anne E Corcoran, Rachael Walker, Iyadh Douagi, Fredrik Lanner, Peter J Rugg-Gunn
Human pluripotent stem cells (PSCs) exist in naive and primed states and provide important models to investigate the earliest stages of human development. Naive cells can be obtained through primed-to-naive resetting, but there are no reliable methods to prospectively isolate unmodified naive cells during this process. Here we report comprehensive profiling of cell surface proteins by flow cytometry in naive and primed human PSCs. Several naive-specific, but not primed-specific, proteins were also expressed by pluripotent cells in the human preimplantation embryo...
March 21, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28343984/amitosis-of-polyploid-cells-regenerates-functional-stem-cells-in-the-drosophila-intestine
#2
Elena M Lucchetta, Benjamin Ohlstein
Organ fitness depends on appropriate maintenance of stem cell populations, and aberrations in functional stem cell numbers are associated with malignancies and aging. Symmetrical division is the best characterized mechanism of stem cell replacement, but other mechanisms could also be deployed, particularly in situations of high stress. Here, we show that after severe depletion, intestinal stem cells (ISCs) in the Drosophila midgut are replaced by spindle-independent ploidy reduction of cells in the enterocyte lineage through a process known as amitosis...
March 18, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28343982/single-cell-5-formylcytosine-landscapes-of-mammalian-early-embryos-and-escs-at-single-base-resolution
#3
Chenxu Zhu, Yun Gao, Hongshan Guo, Bo Xia, Jinghui Song, Xinglong Wu, Hu Zeng, Kehkooi Kee, Fuchou Tang, Chengqi Yi
Active DNA demethylation in mammals involves ten-eleven translocation (TET) family protein-mediated oxidation of 5-methylcytosine (5mC). However, base-resolution landscapes of 5-formylcytosine (5fC) (an oxidized derivative of 5mC) at the single-cell level remain unexplored. Here, we present "CLEVER-seq" (chemical-labeling-enabled C-to-T conversion sequencing), which is a single-cell, single-base resolution 5fC-sequencing technology, based on biocompatible, selective chemical labeling of 5fC and subsequent C-to-T conversion during amplification and sequencing...
March 15, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28330582/adipocyte-accumulation-in-the-bone-marrow-during-obesity-and-aging-impairs-stem-cell-based-hematopoietic-and-bone-regeneration
#4
Thomas H Ambrosi, Antonio Scialdone, Antonia Graja, Sabrina Gohlke, Anne-Marie Jank, Carla Bocian, Lena Woelk, Hua Fan, Darren W Logan, Annette Schürmann, Luis R Saraiva, Tim J Schulz
Aging and obesity induce ectopic adipocyte accumulation in bone marrow cavities. This process is thought to impair osteogenic and hematopoietic regeneration. Here we specify the cellular identities of the adipogenic and osteogenic lineages of the bone. While aging impairs the osteogenic lineage, high-fat diet feeding activates expansion of the adipogenic lineage, an effect that is significantly enhanced in aged animals. We further describe a mesenchymal sub-population with stem cell-like characteristics that gives rise to both lineages and, at the same time, acts as a principal component of the hematopoietic niche by promoting competitive repopulation following lethal irradiation...
March 13, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28285905/targeting-bmi1-cancer-stem-cells-overcomes-chemoresistance-and-inhibits-metastases-in-squamous-cell-carcinoma
#5
Demeng Chen, Mansi Wu, Yang Li, Insoon Chang, Quan Yuan, Mari Ekimyan-Salvo, Peng Deng, Bo Yu, Yongxin Yu, Jiaqiang Dong, John M Szymanski, Sivakumar Ramadoss, Jiong Li, Cun-Yu Wang
Squamous cell carcinoma in the head and neck (HNSCC) is a common yet poorly understood cancer, with adverse clinical outcomes due to treatment resistance, recurrence, and metastasis. Putative cancer stem cells (CSCs) have been identified in HNSCC, and BMI1 expression has been linked to these phenotypes, but optimal treatment strategies to overcome chemotherapeutic resistance and eliminate metastases have not yet been identified. Here we show through lineage tracing and genetic ablation that BMI1(+) CSCs mediate invasive growth and cervical lymph node metastasis in a mouse model of HNSCC...
March 8, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28285904/mex3a-marks-a-slowly-dividing-subpopulation-of-lgr5-intestinal-stem-cells
#6
Francisco M Barriga, Elisa Montagni, Miyeko Mana, Maria Mendez-Lago, Xavier Hernando-Momblona, Marta Sevillano, Amy Guillaumet-Adkins, Gustavo Rodriguez-Esteban, Simon J A Buczacki, Marta Gut, Holger Heyn, Douglas J Winton, Omer H Yilmaz, Camille Stephan-Otto Attolini, Ivo Gut, Eduard Batlle
Highly proliferative Lgr5+ stem cells maintain the intestinal epithelium and are thought to be largely homogeneous. Although quiescent intestinal stem cell (ISC) populations have been described, the identity and features of such a population remain controversial. Here we report unanticipated heterogeneity within the Lgr5+ ISC pool. We found that expression of the RNA-binding protein Mex3a labels a slowly cycling subpopulation of Lgr5+ ISCs that contribute to all intestinal lineages with distinct kinetics. Single-cell transcriptome profiling revealed that Lgr5+ cells adopt two discrete states, one of which is defined by a Mex3a expression program and relatively low levels of proliferation genes...
March 8, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28285903/prc2-facilitates-the-regulatory-topology-required-for-poised-enhancer-function-during-pluripotent-stem-cell-differentiation
#7
Sara Cruz-Molina, Patricia Respuela, Christina Tebartz, Petros Kolovos, Milos Nikolic, Raquel Fueyo, Wilfred F J van Ijcken, Frank Grosveld, Peter Frommolt, Hisham Bazzi, Alvaro Rada-Iglesias
Poised enhancers marked by H3K27me3 in pluripotent stem cells have been implicated in the establishment of somatic expression programs during embryonic stem cell (ESC) differentiation. However, the functional relevance and mechanism of action of poised enhancers remain unknown. Using CRISPR/Cas9 technology to engineer precise genetic deletions, we demonstrate that poised enhancers are necessary for the induction of major anterior neural regulators. Interestingly, circularized chromosome conformation capture sequencing (4C-seq) shows that poised enhancers already establish physical interactions with their target genes in ESCs in a polycomb repressive complex 2 (PRC2)-dependent manner...
February 28, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28196600/genome-editing-in-hpscs-reveals-gata6-haploinsufficiency-and-a-genetic-interaction-with-gata4-in-human-pancreatic-development
#8
Zhong-Dong Shi, Kihyun Lee, Dapeng Yang, Sadaf Amin, Nipun Verma, Qing V Li, Zengrong Zhu, Chew-Li Soh, Ritu Kumar, Todd Evans, Shuibing Chen, Danwei Huangfu
Human disease phenotypes associated with haploinsufficient gene requirements are often not recapitulated well in animal models. Here, we have investigated the association between human GATA6 haploinsufficiency and a wide range of clinical phenotypes that include neonatal and adult-onset diabetes using CRISPR (clustered regularly interspaced short palindromic repeat)/Cas9-mediated genome editing coupled with human pluripotent stem cell (hPSC) directed differentiation. We found that loss of one GATA6 allele specifically affects the differentiation of human pancreatic progenitors from the early PDX1+ stage to the more mature PDX1+NKX6...
February 8, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28196601/cholinergic-signals-from-the-cns-regulate-g-csf-mediated-hsc-mobilization-from-bone-marrow-via-a-glucocorticoid-signaling-relay
#9
Halley Pierce, Dachuan Zhang, Claire Magnon, Daniel Lucas, John R Christin, Matthew Huggins, Gary J Schwartz, Paul S Frenette
Hematopoietic stem cells (HSCs) are mobilized from niches in the bone marrow (BM) to the blood circulation by the cytokine granulocyte colony-stimulating factor (G-CSF) through complex mechanisms. Among these, signals from the sympathetic nervous system regulate HSC egress via its niche, but how the brain communicates with the BM remains largely unknown. Here we show that muscarinic receptor type-1 (Chrm1) signaling in the hypothalamus promotes G-CSF-elicited HSC mobilization via hormonal priming of the hypothalamic-pituitary-adrenal (HPA) axis...
February 4, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28132834/human-ipsc-derived-neural-progenitors-are-an-effective-drug-discovery-model-for-neurological-mtdna-disorders
#10
Carmen Lorenz, Pierre Lesimple, Raul Bukowiecki, Annika Zink, Gizem Inak, Barbara Mlody, Manvendra Singh, Marcus Semtner, Nancy Mah, Karine Auré, Megan Leong, Oleksandr Zabiegalov, Ekaterini-Maria Lyras, Vanessa Pfiffer, Beatrix Fauler, Jenny Eichhorst, Burkhard Wiesner, Norbert Huebner, Josef Priller, Thorsten Mielke, David Meierhofer, Zsuzsanna Izsvák, Jochen C Meier, Frédéric Bouillaud, James Adjaye, Markus Schuelke, Erich E Wanker, Anne Lombès, Alessandro Prigione
Mitochondrial DNA (mtDNA) mutations frequently cause neurological diseases. Modeling of these defects has been difficult because of the challenges associated with engineering mtDNA. We show here that neural progenitor cells (NPCs) derived from human induced pluripotent stem cells (iPSCs) retain the parental mtDNA profile and exhibit a metabolic switch toward oxidative phosphorylation. NPCs derived in this way from patients carrying a deleterious homoplasmic mutation in the mitochondrial gene MT-ATP6 (m.9185T>C) showed defective ATP production and abnormally high mitochondrial membrane potential (MMP), plus altered calcium homeostasis, which represents a potential cause of neural impairment...
January 25, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28132833/nicotinamide-ameliorates-disease-phenotypes-in-a-human-ipsc-model-of-age-related-macular-degeneration
#11
Janmeet S Saini, Barbara Corneo, Justine D Miller, Thomas R Kiehl, Qingjie Wang, Nathan C Boles, Timothy A Blenkinsop, Jeffrey H Stern, Sally Temple
Age-related macular degeneration (AMD) affects the retinal pigment epithelium (RPE), a cell monolayer essential for photoreceptor survival, and is the leading cause of vision loss in the elderly. There are no disease-altering therapies for dry AMD, which is characterized by accumulation of subretinal drusen deposits and complement-driven inflammation. We report the derivation of human-induced pluripotent stem cells (hiPSCs) from patients with diagnosed AMD, including two donors with the rare ARMS2/HTRA1 homozygous genotype...
January 21, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28111200/rna-helicase-ddx5-inhibits-reprogramming-to-pluripotency-by-mirna-based-repression-of-rybp-and-its-prc1-dependent-and-independent-functions
#12
Huanhuan Li, Ping Lai, Jinping Jia, Yawei Song, Qing Xia, Kaimeng Huang, Na He, Wangfang Ping, Jiayu Chen, Zhongzhou Yang, Jiao Li, Mingze Yao, Xiaotao Dong, Jicheng Zhao, Chunhui Hou, Miguel A Esteban, Shaorong Gao, Duanqing Pei, Andrew P Hutchins, Hongjie Yao
RNA-binding proteins (RBPs), in addition to their functions in cellular homeostasis, play important roles in lineage specification and maintaining cellular identity. Despite their diverse and essential functions, which touch on nearly all aspects of RNA metabolism, the roles of RBPs in somatic cell reprogramming are poorly understood. Here we show that the DEAD-box RBP DDX5 inhibits reprogramming by repressing the expression and function of the non-canonical polycomb complex 1 (PRC1) subunit RYBP. Disrupting Ddx5 expression improves the efficiency of iPSC generation and impedes processing of miR-125b, leading to Rybp upregulation and suppression of lineage-specific genes via RYBP-dependent ubiquitination of H2AK119...
January 11, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28111201/human-ipsc-derived-cerebral-organoids-model-cellular-features-of-lissencephaly-and-reveal-prolonged-mitosis-of-outer-radial-glia
#13
Marina Bershteyn, Tomasz J Nowakowski, Alex A Pollen, Elizabeth Di Lullo, Aishwarya Nene, Anthony Wynshaw-Boris, Arnold R Kriegstein
Classical lissencephaly is a genetic neurological disorder associated with mental retardation and intractable epilepsy, and Miller-Dieker syndrome (MDS) is the most severe form of the disease. In this study, to investigate the effects of MDS on human progenitor subtypes that control neuronal output and influence brain topology, we analyzed cerebral organoids derived from control and MDS-induced pluripotent stem cells (iPSCs) using time-lapse imaging, immunostaining, and single-cell RNA sequencing. We saw a cell migration defect that was rescued when we corrected the MDS causative chromosomal deletion and severe apoptosis of the founder neuroepithelial stem cells, accompanied by increased horizontal cell divisions...
January 9, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28257711/dna-damage-induced-hspc-malfunction-depends-on-ros-accumulation-downstream-of-ifn-1-signaling-and-bid-mobilization
#14
Alpaslan Tasdogan, Suresh Kumar, Gabriele Allies, Julia Bausinger, Franziska Beckel, Helmut Hofemeister, Medhanie Mulaw, Vikas Madan, Karin Scharffetter-Kochanek, Michaela Feuring-Buske, Konstanze Doehner, Günter Speit, A Francis Stewart, Hans Joerg Fehling
No abstract text is available yet for this article.
March 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28257710/bringing-a-leukemic-stem-cell-gene-signature-into-clinics-are-we-there-yet
#15
Guillaume Richard-Carpentier, Guy Sauvageau
Prognostic markers that capture leukemia stem cell (LSC) activity can be useful for the risk stratification of acute myeloid leukemia (AML) patients. In a recent issue of Nature, Ng et al. (2016) develop a prognostic score based on a 17-gene expression signature of LSCs to predict outcome in AML patients.
March 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28257709/bridging-the-gaps-ipsc-based-models-from-chip-to-mds-to-aml
#16
Kathrin M Bernt
Myeloid malignancies exist on a spectrum from asymptomatic clonal hematopoiesis to overt leukemia and exhibit substantial clonal heterogeneity. Both aspects are challenging to capture in experimental models. In two landmark studies in this issue of Cell Stem Cell, Kotini et al. (2017) and Chao et al. (2017) establish iPSC-based experimental platforms that recapitulate disease stages and clonal architecture.
March 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28257708/pericytes-or-mesenchymal-stem-cells-is-that-the-question
#17
Elena Cano, Véronique Gebala, Holger Gerhardt
For almost a decade, mesenchymal stem cells (MSCs) were believed to reside as perivascular cells in vivo. In this issue of Cell Stem Cell, Guimarães-Camboa et al. (2017) challenge this idea and use lineage tracing to demonstrate that perivascular cells do not behave as tissue-specific progenitors in various organs, despite showing MSC potential in vitro.
March 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28257707/a-back-door-to-cortical-development
#18
Gerd Kempermann
The mammalian cortex develops in an "inside-out" manner, as neural stem and progenitor cells lining the ventricles build the brain from within. Bifari et al. (2017), in this issue of Cell Stem Cell, find a small set of cortical neurons that appear to originate from radial glia-like progenitors in the meninges, suggesting an outside-in contribution to corticogenesis.
March 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28257706/unveiling-the-role-of-senescence-induced-cellular-plasticity
#19
Jumpei Taguchi, Yasuhiro Yamada
Mice expressing Yamanaka factors develop teratomas containing iPSCs, suggesting that somatic cells are reprogrammable in vivo. Recent studies in Cell, Science, and this issue of Cell Stem Cell (Ocampo et al., 2016; Mosteiro et al., 2016; Chiche et al., 2017, respectively) report crosstalk between reprogramming and senescence, providing insights on cellular plasticity in multicellular organisms.
March 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28257705/unsaturated-fatty-acids-maintain-cancer-cell-stemness
#20
Abir Mukherjee, Hilary A Kenny, Ernst Lengyel
Investigation of the metabolic regulation of cancer stem cells is an emerging field that offers promising approaches for identifying and targeting recalcitrant stem cell populations. In this issue of Cell Stem Cell, Li et al. (2017) indicate that increased lipid desaturation is essential to stem-like characteristics in ovarian cancer cells.
March 2, 2017: Cell Stem Cell
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