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 quiescent "reserve" ISCs contribute to regeneration. By timing the interval between LGR5+ lineage tracing and lethal injury, we show that ISC regeneration is explained nearly completely by dedifferentiation, with contributions from absorptive and secretory progenitors. The ISC-restricted transcription factor ASCL2 confers measurable competitive advantage to resting ISCs and is essential to restore the ISC compartment. Regenerating cells re-express Ascl2 days before Lgr5, and single-cell RNA sequencing (scRNA-seq) analyses reveal transcriptional paths underlying dedifferentiation. ASCL2 target genes include the interleukin-11 (IL-11) receptor Il11ra1, and recombinant IL-11 enhances crypt cell regenerative potential. These findings reveal cell dedifferentiation as the principal means for ISC restoration and highlight an ASCL2-regulated signal that enables this adaptive response.
journal_name
Cell Stem Celljournal_title
Cell stem cellauthors
Murata K,Jadhav U,Madha S,van Es J,Dean J,Cavazza A,Wucherpfennig K,Michor F,Clevers H,Shivdasani RAdoi
10.1016/j.stem.2019.12.011subject
Has Abstractpub_date
2020-03-05 00:00:00pages
377-390.e6issue
3eissn
1934-5909issn
1875-9777pii
S1934-5909(19)30569-7journal_volume
26pub_type
杂志文章相关文献
Cell Stem Cell文献大全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：:Stroma is a largely understudied component of all organs that contributes to stem cell niches. Studies to define stromal components in the bone marrow have led to some unexpected findings that prompt further research. ...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2012.05.011
更新日期：2012-06-14 00:00:00
abstract：:Long noncoding RNAs (lncRNAs) have been described in cell lines and various whole tissues, but lncRNA analysis of development in vivo is limited. Here, we comprehensively analyze lncRNA expression for the adult mouse subventricular zone neural stem cell lineage. We utilize complementary genome-wide techniques includin...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2013.03.003
更新日期：2013-05-02 00:00:00
abstract：:Mesenchymal stem/stromal cells (MSCs) can either suppress or promote tumors. We found previously that incubation of human bone marrow MSCs (hMSCs) with TNF-α upregulated multiple genes including TRAIL, which has cancer apoptotic activity. Here, we show that weekly infusions into mice of hMSCs preactivated with TNF-α i...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2012.10.001
更新日期：2012-12-07 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：:Chronic liver injury can cause cirrhosis and impaired liver regeneration, impairing organ function. Adult livers can regenerate in response to parenchymal insults, and multiple cellular sources have been reported to contribute to this response. In this study, we modeled human chronic liver injuries, in which such resp...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2018.05.022
更新日期：2018-07-05 00:00:00
abstract：:Systems biology studies have revealed transcriptional networks and proteomic signatures critical for embryonic stem cell (ESC) function. In this issue of Cell Stem Cell, Sampath et al. (2008) demonstrate that translation is also differentially controlled in undifferentiated versus differentiated ESCs. ...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2008.04.009
更新日期：2008-05-08 00:00:00
abstract：:The lineage restriction of prospectively isolated hematopoietic progenitors has been traditionally assessed by bulk in vitro culture and transplantation of large number of cells in vivo. These methods, however, cannot distinguish between homogenous multipotent or heterogeneous lineage-restricted populations. Using clo...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2010.02.013
更新日期：2010-04-02 00:00:00
abstract：:Most disease variants lie within noncoding genomic regions, making their functional interpretation challenging. Because chromatin openness strongly influences transcriptional activity, we hypothesized that cell-type-specific open chromatin regions (OCRs) might highlight disease-relevant noncoding sequences. To investi...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2017.07.008
更新日期：2017-09-07 00:00:00
abstract：:Structural and transcriptional changes during early brain maturation follow fixed developmental programs defined by genetics. However, whether this is true for functional network activity remains unknown, primarily due to experimental inaccessibility of the initial stages of the living human brain. Here, we developed ...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2019.08.002
更新日期：2019-10-03 00:00:00
abstract：:In a recent issue of Nature, Tachibana et al. (2009) conducted chromosomal transfer into recipient primate oocytes to yield live offspring or monkey ESCs with no contribution of donor mitochondria. The success of this technique may increase demand for human oocyte donation for research. ...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2009.09.009
更新日期：2009-10-02 00:00:00
abstract：:The metabolic state of quiescent hematopoietic stem cells (HSCs) is an important regulator of self-renewal, but it is unclear whether or how metabolic parameters contribute to HSC lineage specification and commitment. Here, we show that the commitment of human and murine HSCs to the erythroid lineage is dependent upon...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2014.06.002
更新日期：2014-08-07 00:00:00
abstract：:Clonal tracking of hematopoietic stem and progenitor cells (HSPCs) has proven valuable for studying their behavior in murine recipients. Now in Cell Stem Cell, Kim et al. (2014) and Wu et al. (2014) extend these analyses to nonhuman primates, providing insights into dynamics of HSPC expansion and lineage commitment fo...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2014.03.006
更新日期：2014-04-03 00:00:00
abstract：:The current widespread outbreak of Zika virus (ZIKV) infection has been linked to severe clinical birth defects, particularly microcephaly, warranting urgent study of the molecular mechanisms underlying ZIKV pathogenesis. Akt-mTOR signaling is one of the key cellular pathways essential for brain development and autoph...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2016.07.019
更新日期：2016-11-03 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：:Individuals with neurofibromatosis type 1 (NF1) develop abnormalities of both neuronal and glial cell lineages, suggesting that the NF1 protein neurofibromin is an essential regulator of neuroglial progenitor function. In this regard, Nf1-deficient embryonic telencephalic neurospheres exhibit increased self-renewal an...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2007.07.008
更新日期：2007-10-11 00:00:00
abstract：:Technological limitations have hampered understanding of how individual molecules, including putative stem cell regulators, are distributed throughout tissues and stem cell niches. Here, we report adaptation of the proximity ligation assay (PLA) for large-volume, in situ imaging of individual proteins with multiple ad...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2019.10.003
更新日期：2019-12-05 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：:Mammalian embryonic stem cells (ESCs) can self-organize in vitro, but whether they can recreate early embryonic morphogenesis is unclear. Harrison et al. recently demonstrate in Science that 3D co-cultures of mouse ESCs and trophoblast stem cells self-organize into embryo-like structures that recreate many features of...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2017.04.001
更新日期：2017-05-04 00:00:00
abstract：:Ezh2, the methyltransferase within Polycomb Repressive II Complexes, was thought to be essential for all H3K27me3 marks in embryonic stem cells (ESCs). Recently in Molecular Cell, Shen and colleagues (2008) revealed that EZH2 is dispensable for ESC derivation and self-renewal, and that EZH1 may unexpectedly compensate...
journal_title：Cell stem cell
pub_type： 杂志文章,评审
doi：10.1016/j.stem.2008.11.007
更新日期：2008-12-04 00:00:00
abstract：:There is intense contemporary interest in the identity, stability, and potential of stem cells, in the body or in the lab. The unusually comprehensive view provided by the 7th annual meeting of the ISSCR provides a framework to summarize recent progress. ...
journal_title：Cell stem cell
pub_type：
doi：10.1016/j.stem.2009.10.012
更新日期：2009-11-06 00:00:00
abstract：:Stem cells have the capacity to both self-renew and generate postmitotic cells. Long-term tracking of individual clones in their natural environment constitutes the ultimate way to validate postembryonic stem cells. We identify retinal stem cells (RSCs) using the spatiotemporal organization of the fish retina and foll...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2011.11.004
更新日期：2011-12-02 00:00:00
abstract：:Sox family transcription factors have emerged as key regulators of multiple developmental processes, including fate determination and differentiation in multiple tissues. In this issue of Cell Stem Cell, Nowak et al. (2008) implicate Sox9 in the specification of early hair follicle stem cells and subsequent epithelial...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2008.06.014
更新日期：2008-07-03 00:00:00
abstract：:Centralized banking of human embryonic stem (hES) cells is an endeavor that can benefit individual research efforts and enhance international collaboration but is complicated by the fact that the science is rapidly evolving in an environment of heterogeneous laws, guidelines, and ethical standards. Written from the va...
journal_title：Cell stem cell
pub_type： 杂志文章,评审
doi：10.1016/j.stem.2008.03.018
更新日期：2008-04-10 00:00:00
abstract：:Production of new neurons in the adult hippocampus decreases with age; this decline may underlie age-related cognitive impairment. Here we show that continuous depletion of the neural stem cell pool, as a consequence of their division, may contribute to the age-related decrease in hippocampal neurogenesis. Our results...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2011.03.010
更新日期：2011-05-06 00:00:00
abstract：:Polycomb group (PcG) proteins are essential regulators of stem cells. PcG and trithorax group proteins mark developmental regulator gene promoters with bivalent domains consisting of overlapping repressive and activating histone modifications to keep them poised for activation in embryonic stem cells. Bmi1, a componen...
journal_title：Cell stem cell
pub_type： 杂志文章
doi：10.1016/j.stem.2010.01.005
更新日期：2010-03-05 00:00:00
abstract：:Exit from the naive pluripotent state occurs through a series of changes in the gene regulatory circuitry, allowing cells to become primed for lineage commitment. In this issue of Cell Stem Cell, Kalkan et al. (2019) show that three transcription regulators are required for naive mouse embryonic stem cells (ESCs) to e...
journal_title：Cell stem cell
pub_type： 评论,杂志文章
doi：10.1016/j.stem.2019.04.008
更新日期：2019-05-02 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：:Cancer stem cells (CSCs) are tumor cells that have the principal properties of self-renewal, clonal tumor initiation capacity, and clonal long-term repopulation potential. CSCs reside in niches, which are anatomically distinct regions within the tumor microenvironment. These niches maintain the principle properties of...
journal_title：Cell stem cell
pub_type： 杂志文章,评审
doi：10.1016/j.stem.2015.02.015
更新日期：2015-03-05 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
