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Showing papers in "Cell Stem Cell in 2014"


Journal ArticleDOI
TL;DR: It is proposed that the genetic and CSC models of cancer can be harmonized by considering the role of genetic diversity and nongenetic influences in contributing to tumor heterogeneity.

1,833 citations


Journal ArticleDOI
TL;DR: F Fate-mapping showed that LepR(+) cells arose postnatally and gave rise to most bone and adipocytes formed in adult bone marrow, including bone regenerated after irradiation or fracture.

971 citations


Journal ArticleDOI
TL;DR: Mapping the m( 6)A methylome in mouse and human embryonic stem cells reveals the evolutionary conservation and function of m(6)A, a mark of transcriptome flexibility required for stem cells to differentiate to specific lineages.

906 citations



Journal ArticleDOI
TL;DR: In this paper, the authors identify small molecules that support self-renewal of naive human ESCs based on maintenance of endogenous OCT4 distal enhancer activity, a molecular signature of ground state pluripotency.

682 citations


Journal ArticleDOI
TL;DR: By reevaluating the developmental origins of metanephric progenitors, this work has provided key insights into kidney specification in vivo and taken important steps toward kidney organogenesis in vitro.

679 citations


Journal ArticleDOI
Ziyuan Guo1, Lei Zhang1, Zheng Wu1, Yuchen Chen1, Fan Wang1, Gong Chen1 
TL;DR: It is shown that reactive glial cells in the cortex of stab-injured or Alzheimer's disease model mice can be directly reprogrammed into functional neurons in vivo using retroviral expression of a single neural transcription factor, NeuroD1.

630 citations


Journal ArticleDOI
TL;DR: It is shown that all colorectal cancer stem cells (CR-CSCs) express CD44v6, which is required for their migration and generation of metastatic tumors, and phosphatidylinositol 3-kinase (PI3K) inhibition selectively killed CD 44v6 CR-C SCs and reduced metastatic growth.

597 citations


Journal ArticleDOI
TL;DR: By dissecting the biology of this process, vulnerabilities are being exposed that could be exploited to prevent metastasis.

568 citations


Journal ArticleDOI
TL;DR: A comprehensive integrated genomic analysis of young and aged HSCs showed increased DNA methylation at transcription factor binding sites associated with differentiation-promoting genes combined with a reduction at genes associated with HSC maintenance, paralleling phenotypic HSC aging behavior.

493 citations


Journal ArticleDOI
TL;DR: It is suggested that, although some cell types may be at risk for off-target mutations, the incidence of such effects in human pluripotent stem cells may be sufficiently low and thus not a significant concern for disease modeling and other applications.


Journal ArticleDOI
TL;DR: Upon transplantation into mice with concanavalin-A-induced acute liver failure and fatal metabolic liver disease due to fumarylacetoacetate dehydrolase (Fah) deficiency, hiHeps restore the liver function and prolong survival.

Journal ArticleDOI
TL;DR: Evidence supporting and refuting whether self-renewable and bipotential liver stem cells exist in development, homeostasis, regeneration, and disease is discussed.

Journal ArticleDOI
TL;DR: It is argued that Lgr5(-) reserve stem cells are radiosensitive and that L gr5(+) cells are crucial for robust intestinal regeneration following radiation exposure but are dispensable for premalignant hyperproliferation.

Journal ArticleDOI
TL;DR: Evidence showing that lncRNAs exert critical functions in adult tissue stem cells, including skin, brain, and muscle, as well as in developmental patterning and pluripotency is reviewed.

Journal ArticleDOI
TL;DR: The iCRISPR platform is uniquely suited for dissection of complex genetic interactions and pleiotropic gene functions in human disease studies and has the potential to support high-throughput genetic analysis in hPSCs.

Journal ArticleDOI
TL;DR: It is demonstrated that transition between these two pluripotent states is associated with widespread Oct4 relocalization, mirrored by global rearrangement of enhancer chromatin landscapes, and suggested that the capacity of transcription factors such as Otx2 and Oct4 to pioneer new enhancer sites is highly context dependent.

Journal ArticleDOI
TL;DR: An unexpectedly dynamic pattern of transcript isoform regulation is found, suggesting a critical regulatory role during HSC differentiation, and a cell cycle/DNA repair signature associated with multipotency in MPP2 cells is found.

Journal ArticleDOI
TL;DR: It is concluded that human and mouse hepatocytes can undergo reversible ductal metaplasia in response to injury, expand as ducts, and subsequently contribute to restoration of the hepatocyte mass.

Journal ArticleDOI
TL;DR: It is suggested that in the glioma perivascular niche, osteopontin promotes stem cell-like properties and radiation resistance in adjacent tumor cells via activation of CD44 signaling.

Journal ArticleDOI
TL;DR: The diversity in MSC-based clinical trial product proposals is discussed and potential challenges for clinical translation are highlighted.

Journal ArticleDOI
TL;DR: Reprogramming and stem cell differentiation approaches with genome engineering and RNA sequencing are combined to define the transcriptional and functional changes that are induced in human motor neurons by mutant SOD1, indicating that at least a subset of these changes are more broadly conserved in ALS.

Journal ArticleDOI
TL;DR: A porcine model of acute myocardial infarction is utilized to investigate the functional impact of intramyocardial transplantation of hiPSC-derived cardiomyocytes, endothelial cells, and smooth muscle cells, in combination with a 3D fibrin patch loaded with insulin growth factor (IGF)-encapsulated microspheres.

Journal ArticleDOI
TL;DR: The relationship between genome organization and lineage-specific transcriptional regulation is discussed in this paper, where the authors argue that the two are inextricably linked and that the relationship can be seen as a direct consequence of 3D genome organization.

Journal ArticleDOI
TL;DR: It is demonstrated that HSCs are not comprehensively geno-protected during aging, and HSC quiescence and concomitant attenuation of DNA repair and response pathways underlies DNA damage accumulation in H SCs during aging.

Journal ArticleDOI
TL;DR: It is reported that, contrary to prevailing stem-cell-based models of regeneration, virtually all new hepatocytes come from preexisting hepatocytes.

Journal ArticleDOI
TL;DR: It is shown that hESC-derived dopamine neurons can project sufficiently long distances for use in humans, fully regenerate midbrain-to-forebrain projections, and innervate correct target structures, providing strong preclinical support for clinical translation of hESCs using approaches similar to those established with fetal cells for the treatment of Parkinson’s disease.

Journal ArticleDOI
TL;DR: It is shown that prolonged fasting reduces circulating IGF-1 levels and PKA activity in various cell populations, leading to signal transduction changes in long-term hematopoietic stem cells and niche cells that promote stress resistance, self-renewal, and lineage-balanced regeneration.

Journal ArticleDOI
TL;DR: The most commonly used system consists of a single polypeptide endonuclease Cas9 complexed with a single guide RNA (gRNA) that provides complementarity to 20-nucleotide target DNA sequence as mentioned in this paper.