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Showing papers in "Cell Stem Cell in 2010"


Journal ArticleDOI
TL;DR: It is shown that this approach can reprogram multiple human cell types to pluripotency with efficiencies that greatly surpass established protocols and represents a safe, efficient strategy for somatic cell reprogramming and directing cell fate that has broad applicability for basic research, disease modeling, and regenerative medicine.

2,627 citations


Journal ArticleDOI
TL;DR: The Lgr5 stem cell marker and culture method described here will be invaluable tools for accelerating research into gastric epithelial renewal, inflammation/infection, and cancer.

1,342 citations


Journal ArticleDOI
TL;DR: This work has identified a broader spectrum of stem cells influenced by hypoxia that includes cancer stem cells and induced pluripotent stem cells, and elucidate an added dimension of stem cell control within the niche.

1,332 citations


Journal ArticleDOI
TL;DR: It is shown that the majority of the newborn cells undergo death by apoptosis in the first 1 to 4 days of their life, during the transition from amplifying neuroprogenitors to neuroblasts, which suggests a new role for microglia in maintaining the homeostasis of the baseline neurogenic cascade.

1,322 citations


Journal ArticleDOI
TL;DR: It is shown that the generation of iPSCs from mouse fibroblasts requires a mesenchymal-to-epithelial transition (MET) orchestrated by suppressing pro-EMT signals from the culture medium and activating an epithelial program inside the cells.

1,083 citations


Journal ArticleDOI
TL;DR: It is shown that LT-HSCs utilize glycolysis instead of mitochondrial oxidative phosphorylation to meet their energy demands and that Meis1 regulates HSC metabolism through transcriptional activation of Hif-1alpha.

920 citations


Journal ArticleDOI
TL;DR: It is reported that a natural compound, vitamin C (Vc), enhances iPSC generation from both mouse and human somatic cells, acts at least in part by alleviating cell senescence, a recently identified roadblock for reprogramming.

913 citations


Journal ArticleDOI
TL;DR: A multistep mechanism that incorporates a BMP-miRNA-MET axis during somatic cell reprogramming is defined that is linked to B MP-dependent induction of miR-205 and themiR-200 family of microRNAs that are key regulators of MET.

891 citations


Journal ArticleDOI
TL;DR: By comparing the chromatin-modification profiles and DNA methylomes in hESCs and primary fibroblasts, it is found that nearly one-third of the genome differs in chromatin structure.

810 citations


Journal ArticleDOI
TL;DR: It is shown that normal HSCs maintain intracellular hypoxia and stabilize Hypoxia-inducible factor-1 alpha (HIF-1alpha) protein, which indicates that H SCs maintain cell cycle quiescence through the precise regulation of HIF- 1alpha levels.

808 citations


Journal ArticleDOI
TL;DR: A third type of aneuploidy already evident in early passage HiPSCs is revealed, suggesting considerable selective pressure during the reprogramming process, and high incidence of chromosome 12 duplications is indicated, resulting in significant enrichment for cell cycle-related genes.

Journal ArticleDOI
TL;DR: It is demonstrated that deleting Brca1 in mouse mammary epithelial luminal progenitors produces tumors that phenocopy human BRCA1 breast cancers and that when target cells for transformation have the potential for phenotypic plasticity, tumor phenotypes may not directly reflect histogenesis.

Journal ArticleDOI
TL;DR: The power of genome-wide analysis of complex binding patterns and combinatorial interactions for ten key regulators of blood stem/progenitor cells is reported, providing the most comprehensive TF data set for any adult stem/ Progenitor cell type to date.

Journal ArticleDOI
TL;DR: Surprisingly, reduced neurogenesis correlates with a loss of active horizontal NSCs in aged mice rather than a total loss of stem cells, and the transition to a quiescent state is reversible to rejuvenate Neurogenesis in the brain.

Journal ArticleDOI
TL;DR: This review presents the currently available experimental data that connect PcG protein function with some of the key processes which govern somatic stem cell activity and highlights recent studies suggesting that a delicate balance in P cG gene dosage is crucial for proper stem cell homeostasis and prevention of cancer stem cell development.

Journal ArticleDOI
TL;DR: A small molecule cocktail is reported that enables reprogramming of human primary somatic cells to iPSCs with exogenous expression of only OCT4, and mechanistic studies revealed that modulation of cell metabolism from mitochondrial oxidation to glycolysis plays an important role in reprograming.

Journal ArticleDOI
TL;DR: Angiogenic models are developed to demonstrate that EC-derived angiocrine growth factors support in vitro self-renewal and in vivo repopulation of authentic LT-HSCs, and establish an instructive vascular niche for clinical-scale expansion of LT- HSCs and a cellular platform to identify stem cell-active trophogens.

Journal ArticleDOI
TL;DR: Evidence is provided that GSCs express high levels of integrin alpha6, which can serve not only as an enrichment marker but also as a promising antiglioblastoma therapy, and this work identified integrinalpha6 as a candidate for anti-tumor therapy.

Journal ArticleDOI
TL;DR: A manuscript has appeared online demonstrating isolation of iPSCs from peripheral blood, including a single line that showed evidence for both T CR-β and TCR-γ rearrangement by PCR.

Journal ArticleDOI
TL;DR: This work has used Cre-lox fate mapping in transgenic mice to show that PDGFRA/NG2-expressing glia, a distributed population of stem/progenitor cells in the adult CNS, produce the remyelinating oligodendrocytes and almost all of the Schwann cells in chemically induced demyelinated lesions.

Journal ArticleDOI
TL;DR: An improved affinity protocol is used to purify Oct4-interacting proteins from mouse embryonic stem cells to bring greater definition to the circuitry controlling pluripotent cell identity and finds that Esrrb associated with the basal transcription machinery and also detect interactions between transcription factors and components of the TGF-β, Notch, and Wnt signaling pathways.

Journal ArticleDOI
TL;DR: An integrated view of how several distinct cell types contribute in complementary ways to cell maintenance and the reaction to injury is provided.

Journal ArticleDOI
TL;DR: This study demonstrates definitive isolation of lineage-biased HSC subtypes and contributes to the fundamental change in view that the hematopoietic system is maintained by a continuum of H SC subtypes, rather than a functionally uniform pool.

Journal ArticleDOI
TL;DR: Significant molecular transitions and major changes in transcript variants are detected, which include genes for general metabolism and changes in microRNAs, which may contribute to a switch from a normal developmental program in adult cells during the formation of diseased tissues, including cancers.

Journal ArticleDOI
TL;DR: It is found that HSCs have unique cell-intrinsic mechanisms ensuring their survival in response to ionizing irradiation (IR), which include enhanced prosurvival gene expression and strong activation of p53-mediated DNA damage response.

Journal ArticleDOI
TL;DR: A subpopulation of CD26(+) cells uniformly present in both the primary and metastatic tumors in colorectal cancer patients with liver metastasis is identified and the ability to predict metastasis based on analysis of CSC subsets in the primary tumor may have important clinical implication as a selection criterion for adjuvant therapy.

Journal ArticleDOI
TL;DR: The potential role of nitric oxide activity in the perivascular niche (PVN) using a genetic engineered mouse model of PDGF-induced gliomas and the NO/cGMP/PKG pathway's promotion of stem cell-like character in the tumor PVN may identify therapeutic targets for this subset ofgliomas.

Journal ArticleDOI
TL;DR: It is shown that the orphan nuclear receptor Nr5a2 (also known as Lrh-1) can replace Oct4 in the derivation of iPSCs from mouse somatic cells, and it can also enhance reprogramming efficiency.

Journal ArticleDOI
TL;DR: Gene expression profiles confirm that the transcriptional programs of ESCs and iPSCs show very few consistent differences, and some variation in chromatin structure and gene expression was observed in these cell lines, but these variations did not serve to distinguish ESCs fromiPSCs.

Journal ArticleDOI
TL;DR: It is shown that bone morphogenetic protein (BMP) signaling is active in hippocampal NSCs, downstream of BMPR-IA, and is required to balance NSC quiescence/proliferation and to prevent loss of the stem cell activity that supports continuous neurogenesis in the mature hippocampus.