Abstract：
:The Wnt signaling pathway controls stem cell identity in the intestinal epithelium and in many other adult organs. The transcription factor Ascl2 (a Wnt target gene) is a master regulator of intestinal stem cell identity. It is unclear how the continuous Wnt gradient along the crypt axis is translated into discrete expression of Ascl2 and discrete specification of stem cells at crypt bottoms. We show that (1) Ascl2 is regulated in a direct autoactivatory loop, leading to a distinct on/off expression pattern, and (2) Wnt/R-spondin can activate this regulatory loop. This mechanism interprets the Wnt levels in the intestinal crypt and translates the continuous Wnt signal into a discrete Ascl2 "on" or "off" decision. In turn, Ascl2, together with β-catenin/Tcf, activates the genes fundamental to the stem cell state. In this manner, Ascl2 forms a transcriptional switch that is both Wnt responsive and Wnt dependent to define stem cell identity.
journal_name
Cell Stem Celljournal_title
Cell stem cellauthors
Schuijers J,Junker JP,Mokry M,Hatzis P,Koo BK,Sasselli V,van der Flier LG,Cuppen E,van Oudenaarden A,Clevers Hdoi
10.1016/j.stem.2014.12.006subject
Has Abstractpub_date
2015-02-05 00:00:00pages
158-70issue
2eissn
1934-5909issn
1875-9777pii
S1934-5909(14)00564-5journal_volume
16pub_type
杂志文章相关文献
Cell Stem Cell文献大全abstract：:Ablation of LGR5+ intestinal stem cells (ISCs) is associated with rapid restoration of the ISC compartment. Different intestinal crypt populations dedifferentiate to provide new ISCs, but the transcriptional and signaling trajectories that guide this process are unclear, and a large body of work suggests that quiescen...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2019.12.011
更新日期：2020-03-05 00:00:00
abstract：:Heterogeneity within the self-renewal durability of adult hematopoietic stem cells (HSCs) challenges our understanding of the molecular framework underlying HSC function. Gene expression studies have been hampered by the presence of multiple HSC subtypes and contaminating non-HSCs in bulk HSC populations. To gain deep...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2015.04.004
更新日期：2015-06-04 00:00:00
abstract：:In response to muscle injury, satellite cells activate the p38α/β MAPK pathway to exit quiescence, then proliferate, repair skeletal muscle, and self-renew, replenishing the quiescent satellite cell pool. Although satellite cells are capable of asymmetric division, the mechanisms regulating satellite cell self-renewal...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2012.05.025
更新日期：2012-10-05 00:00:00
abstract：:Developmental abnormalities, cancer, and premature aging each have been linked to defects in the DNA damage response (DDR). Mutations in the ATR checkpoint regulator cause developmental defects in mice (pregastrulation lethality) and humans (Seckel syndrome). Here we show that eliminating ATR in adult mice leads to de...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2007.03.002
更新日期：2007-06-07 00:00:00
abstract：:Minority subpopulations within embryonic stem cell cultures display an expanded developmental potential similar to that of early embryo blastomeres or the early inner cell mass. The ability to isolate and culture totipotent cells capable of giving rise to the entire conceptus would enhance our capacity to study early ...
journal_title：Cell stem cell
pub_type： 杂志文章,评审
doi：10.1016/j.stem.2017.12.011
更新日期：2018-01-04 00:00:00
abstract：:The discovery that phenotypic diversity among differentiated cells results from epigenetic and not genetic differences, and can be reset to restore pluripotency, promises revolutionary advances in medicine. I discuss how this and related seminal discoveries have brought us to an exciting future. ...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2012.11.014
更新日期：2012-12-07 00:00:00
abstract：:Recently in Cell, Mitalipov and colleagues report an advance that has eluded scientists for over a decade-the successful derivation of embryonic stem cell lines using somatic cell nuclear transfer, or SCNT (Tachibana et al., 2013). ...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2013.05.022
更新日期：2013-06-06 00:00:00
abstract：:About half of the human genome consists of highly repetitive elements, most of which are considered dispensable for human life. Here, we report that repetitive elements originating from endogenous retroviruses (ERVs) are systematically transcribed during human early embryogenesis in a stage-specific manner. Our analys...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2015.01.005
更新日期：2015-02-05 00:00:00
abstract：VIDEO ABSTRACT:Although endogenous recruitment of adult neural stem cells has been proposed as a therapeutic strategy, clinical approaches for achieving this are lacking. Here, we show that metformin, a widely used drug, promotes neurogenesis and enhances spatial memory formation. Specifically, we show that an atypical...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2012.03.016
更新日期：2012-07-06 00:00:00
abstract：:Stem cell researchers commonly use human pluripotent stem cell lines derived by other investigators. Researchers may use lines derived elsewhere, provided that their derivation met consensus core standards. Some types of derivation raise heightened levels of ethical concern and require greater scrutiny. To maintain pu...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2009.01.013
更新日期：2009-02-06 00:00:00
abstract：:Human pluripotent stem cells (PSCs) could potentially provide a potentially unlimited supply of T cells. In this issue of Cell Stem Cell, Montel-Hagen et al. (2019) take advantage of a three-dimensional mouse stromal cell-based system that combines mesoderm specification with organoid-induced hematopoietic differentia...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2019.02.013
更新日期：2019-03-07 00:00:00
abstract：:Mammalian skin is a complex and heterogeneous tissue with several distinct compartments and stem cell populations. Joost et al. (2016) now use single-cell RNaseq to comprehensively reconstruct this complexity, revealing spatial and pseudotemporal differences between transcriptional programs in distinct compartments an...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2016.09.009
更新日期：2016-10-06 00:00:00
abstract：:Organoids derived from human pluripotent stem cells are a potentially powerful tool for high-throughput screening (HTS), but the complexity of organoid cultures poses a significant challenge for miniaturization and automation. Here, we present a fully automated, HTS-compatible platform for enhanced differentiation and...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2018.04.022
更新日期：2018-06-01 00:00:00
abstract：:Organ growth requires a careful balance between stem cell self-renewal and lineage commitment to ensure proper tissue expansion. The cellular and molecular mechanisms that mediate this balance are unresolved in most organs, including skeletal muscle. Here we identify a long-lived stem cell pool that mediates growth of...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2017.06.003
更新日期：2017-07-06 00:00:00
abstract：:The mouse placenta was unveiled as an important reservoir for hematopoietic stem cells (HSCs), yet the origin of placental HSCs was unknown. By tracking developing HSCs by expression of Runx1-lacZ and CD41, we have found that HSCs emerge in large vessels in the placenta. Analysis of Ncx1(-/-) embryos, which lack a hea...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2008.01.001
更新日期：2008-03-06 00:00:00
abstract：:In this issue of Cell Stem Cell, Pei et al. (2018) demonstrate that leukemic stem cells (LSCs) have enhanced mitochondrial fission, which is positively regulated by FIS1. FIS1 is necessary to maintain LSC function; thus, targeting its expression and mitochondrial fission is a novel approach to decrease stemness and in...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2018.05.026
更新日期：2018-07-05 00:00:00
abstract：:Fanconi anemia (FA) is an inherited DNA repair disorder characterized by progressive bone marrow failure (BMF) from hematopoietic stem and progenitor cell (HSPC) attrition. A greater understanding of the pathogenesis of BMF could improve the therapeutic options for FA patients. Using a genome-wide shRNA screen in huma...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2016.03.002
更新日期：2016-05-05 00:00:00
abstract：:Reconstructing lineage relationships between cells within a tissue or organism is a long-standing aim in biology. Traditionally, lineage tracing has been achieved through the (genetic) labeling of a cell followed by the tracking of its offspring. Currently, lineage trajectories can also be predicted using single-cell ...
journal_title：Cell stem cell
pub_type： 杂志文章,评审
doi：10.1016/j.stem.2018.04.014
更新日期：2018-08-02 00:00:00
abstract：:In this issue of Cell Stem Cell, Feng et al. (2013) report that the gene mutated in human CHARGE syndrome, ATP-dependent chromatin remodeling factor CHD7, contributes to the control of neurogenesis. The authors also report that exercise ameliorates these defects and suggest it as an intervention worthy of study in CHA...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2013.06.010
更新日期：2013-07-03 00:00:00
abstract：:Human induced pluripotent stem cells (hiPSCs) hold promise for myocardial repair following injury, but preclinical studies in large animal models are required to determine optimal cell preparation and delivery strategies to maximize functional benefits and to evaluate safety. Here, we utilized a porcine model of acute...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2014.11.009
更新日期：2014-12-04 00:00:00
abstract：:Inducing immune tolerance to prevent rejection is a key step toward successful engraftment of stem-cell-derived tissue in a clinical setting. Using human pluripotent stem cells to generate thymic epithelial cells (TECs) capable of supporting T cell development represents a promising approach to reach this goal; howeve...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2013.04.004
更新日期：2013-08-01 00:00:00
abstract：:The study of gastric epithelial homeostasis and cancer has been hampered by the lack of stem cell markers and in vitro culture methods. The Wnt target gene Lgr5 marks stem cells in the small intestine, colon, and hair follicle. Here, we investigated Lgr5 expression in the stomach and assessed the stem cell potential o...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2009.11.013
更新日期：2010-01-08 00:00:00
abstract：:Recent studies have shown that tissue-specific stem cells (SCs) found throughout the body respond differentially to DNA damage. In this review, we will discuss how different SC populations sense and functionally respond to DNA damage, identify various common and distinct mechanisms utilized by tissue-specific SCs to a...
journal_title：Cell stem cell
pub_type： 杂志文章,评审
doi：10.1016/j.stem.2010.12.012
更新日期：2011-01-07 00:00:00
abstract：:Stem cell-based therapies for Parkinson's disease are moving into a new and exciting era, with several groups pursuing clinical trials with pluripotent stem cell (PSC)-derived dopamine neurons. As many groups have ongoing or completed GMP-level cell manufacturing, we highlight key clinical translation considerations f...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2017.09.014
更新日期：2017-11-02 00:00:00
abstract：:Leukemia stem cells (LSCs) play a pivotal role in the resistance of chronic myeloid leukemia (CML) to tyrosine kinase inhibitors (TKIs) and its progression to blast crisis (BC), in part, through the alternative splicing of self-renewal and survival genes. To elucidate splice-isoform regulators of human BC LSC maintena...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2012.12.011
更新日期：2013-03-07 00:00:00
abstract：:Cardiac stem/progenitor cells hold great potential for regenerative therapies; however, the mechanisms regulating their expansion and differentiation remain insufficiently defined. Here we show that Ldb1 is a central regulator of genome organization in cardiac progenitor cells, which is crucial for cardiac lineage dif...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2015.08.007
更新日期：2015-09-03 00:00:00
abstract：:In a pioneering study in New England Journal of Medicine, Schweitzer et al. (2020) report on a patient with Parkinson's disease who received a graft of dopamine neurons obtained from in vitro differentiated induced pluripotent stem cells, derived from the patient's own skin fibroblasts, showing the feasibility of auto...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2020.06.008
更新日期：2020-07-02 00:00:00
abstract：:Somatic cell nuclear transfer (SCNT) enables cloning of differentiated cells by reprogramming their nuclei to a totipotent state. However, successful full-term development of SCNT embryos is a low-efficiency process and arrested embryos frequently exhibit epigenetic abnormalities. Here, we generated genome-wide DNA me...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2018.07.017
更新日期：2018-09-06 00:00:00
abstract：:Stem-cell-derived tissues could transform disease research and therapy, yet most methods generate functionally immature products. We investigate how human pluripotent stem cells (hPSCs) differentiate into pancreatic islets in vitro by profiling DNA methylation, chromatin accessibility, and histone modification changes...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2019.11.011
更新日期：2020-01-02 00:00:00
abstract：:Large cutaneous and non-healing ulcers exhibit impaired epithelialization, which represents a major therapeutic challenge. Recently in Nature, Kurita et al. (2018) reported a surprising potential source of epithelial cells. The authors demonstrate that wound-resident mesenchymal cells can be reprogrammed to generate e...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2018.10.014
更新日期：2018-11-01 00:00:00
