Abstract：
:Enhancers are the primary determinants of cell identity, but the regulatory components controlling enhancer turnover during lineage commitment remain largely unknown. Here we compare the enhancer landscape, transcriptional factor occupancy, and transcriptomic changes in human fetal and adult hematopoietic stem/progenitor cells and committed erythroid progenitors. We find that enhancers are modulated pervasively and direct lineage- and stage-specific transcription. GATA2-to-GATA1 switch is prevalent at dynamic enhancers and drives erythroid enhancer commissioning. Examination of lineage-specific enhancers identifies transcription factors and their combinatorial patterns in enhancer turnover. Importantly, by CRISPR/Cas9-mediated genomic editing, we uncover functional hierarchy of constituent enhancers within the SLC25A37 super-enhancer. Despite indistinguishable chromatin features, we reveal through genomic editing the functional diversity of several GATA switch enhancers in which enhancers with opposing functions cooperate to coordinate transcription. Thus, genome-wide enhancer profiling coupled with in situ enhancer editing provide critical insights into the functional complexity of enhancers during development.
journal_name
Dev Celljournal_title
Developmental cellauthors
Huang J,Liu X,Li D,Shao Z,Cao H,Zhang Y,Trompouki E,Bowman TV,Zon LI,Yuan GC,Orkin SH,Xu Jdoi
10.1016/j.devcel.2015.12.014subject
Has Abstractpub_date
2016-01-11 00:00:00pages
9-23issue
1eissn
1534-5807issn
1878-1551journal_volume
36pub_type
杂志文章abstract：:Zebrafish is a powerful model for forward genetics. Reverse genetic approaches are limited by the time required to generate stable mutant lines. We describe a system for gene knockout that consistently produces null phenotypes in G0 zebrafish. Yolk injection of sets of four CRISPR/Cas9 ribonucleoprotein complexes redu...
journal_title：Developmental cell
pub_type： 杂志文章
doi：10.1016/j.devcel.2018.06.003
更新日期：2018-07-02 00:00:00
abstract：:Selection of the correct targets for myelination and regulation of myelin sheath growth are essential for central nervous system (CNS) formation and function. Through a genetic screen in zebrafish and complementary analyses in mice, we find that loss of oligodendrocyte Neurofascin leads to mistargeting of myelin to ce...
journal_title：Developmental cell
pub_type： 杂志文章
doi：10.1016/j.devcel.2019.10.016
更新日期：2019-12-16 00:00:00
abstract：:Many different intercellular signaling pathways are known but, for most, it is unclear whether they can generate oscillating cell behaviors. Here we use time-lapse analysis of Drosophila embryogenesis to show that oenocytes delaminate from the ectoderm in discrete bursts of three. This pulsatile process has a 1 hour p...
journal_title：Developmental cell
pub_type： 杂志文章
doi：10.1016/j.devcel.2004.10.016
更新日期：2004-12-01 00:00:00
abstract：:The interchromosome domain (ICD) model proposes that genes are selectively positioned at the surfaces of chromosome territories to facilitate their regulation. A paper in the May 13 issue of the Journal of Cell Biology provides evidence that supports a reinterpretation of this model. ...
journal_title：Developmental cell
pub_type： 杂志文章
doi：10.1016/s1534-5807(02)00196-x
更新日期：2002-06-01 00:00:00
abstract：:The insulin-like peptide (ILP) family plays key biological roles in the control of body growth. Although the functions of ILPs are well understood, the mechanisms by which organisms sense their nutrient status and thereby control ILP production remain largely unknown. Here, we show that signaling relay and feedback me...
journal_title：Developmental cell
pub_type： 杂志文章
doi：10.1016/j.devcel.2015.10.003
更新日期：2015-11-09 00:00:00
abstract：:Orientation of cell division is a vital aspect of tissue morphogenesis and growth. Asymmetric divisions generate cell fate diversity and epithelial stratification, whereas symmetric divisions contribute to tissue growth, spreading, and elongation. Here, we describe a mechanism for positioning the spindle in symmetric ...
journal_title：Developmental cell
pub_type： 杂志文章
doi：10.1016/j.devcel.2012.01.002
更新日期：2012-04-17 00:00:00
abstract：:The expression of autophagy and lysosomal genes is coordinated by the transcription factor EB (TFEB). In this issue of Developmental Cell, Chen et al. identify an evolutionary conserved mode of TFEB regulation, which entails the inhibition of TFEB phase separation in the nucleus by inositol polyphosphate multikinase. ...
journal_title：Developmental cell
pub_type： 杂志文章
doi：10.1016/j.devcel.2020.11.005
更新日期：2020-12-07 00:00:00
abstract：:The actin remodeling factor N-WASP is best known as an Arp2/3 complex activator in processes like endocytosis, extracellular matrix degradation, and host-pathogen interaction. In this issue of Developmental Cell, Juin et al. establish a novel trafficking function for N-WASP in driving lysophosphatidic acid-dependent c...
journal_title：Developmental cell
pub_type： 评论,杂志文章
doi：10.1016/j.devcel.2019.10.029
更新日期：2019-11-18 00:00:00
abstract：:In response to cellular stress, mitochondria remodel their structure by organelle division and fusion. In this issue of Developmental Cell, Cooper et al. (2014) report that a nuclear protein, cyclin C, is recruited from nuclei to mitochondria upon oxidative stress and promotes mitochondrial division and apoptosis of t...
journal_title：Developmental cell
pub_type： 评论,杂志文章
doi：10.1016/j.devcel.2014.01.010
更新日期：2014-01-27 00:00:00
abstract：:Drosophila gurken mRNA is localized by dynein-mediated transport to a crescent near the oocyte nucleus, thus targeting the TGFalpha signal and forming the primary embryonic axes. Here, we show that gurken and the I factor, a non-LTR retrotransposon, share a small consensus RNA stem loop of defined secondary structure,...
journal_title：Developmental cell
pub_type： 杂志文章
doi：10.1016/j.devcel.2005.04.012
更新日期：2005-07-01 00:00:00
abstract：:Because mitochondria have outer and inner membranes, the fusion of two mitochondria requires the coordinated fusion of four lipid bilayers. Fusion of the outer membranes requires mitofusins. A new study published in Cell (Meeusen et al., 2006) shows that inner membrane fusion requires the dynamin-related protein Mgm1/...
journal_title：Developmental cell
pub_type： 杂志文章
doi：10.1016/j.devcel.2006.10.009
更新日期：2006-11-01 00:00:00
abstract：:The combination of fluid and mechanical properties exhibited by cell membranes enables a wealth of physical phenomena, many of which also have biological functions. A recent study in Cell (Shi et al., 2018) now shows that membrane tension in the cell may not be as simple as it first seemed. ...
journal_title：Developmental cell
pub_type： 评论,杂志文章
doi：10.1016/j.devcel.2018.12.011
更新日期：2019-01-07 00:00:00
abstract：:The intricate interplay between NF-kappaB and JNK determines TNF-alpha cytotoxicity. In a recent Cell paper, report that prolonged JNK1 activation promotes TNF-alpha killing via E3 ligase-mediated degradation of the caspase 8 inhibitor cFLIP(L). On the other hand, Ventura et al. (2006) show in their recent Molecular C...
journal_title：Developmental cell
pub_type： 杂志文章
doi：10.1016/j.devcel.2006.02.006
更新日期：2006-03-01 00:00:00
abstract：:How cold-blooded animals acclimate to temperature and what determines the limits of their viable temperature range are not understood. Here, we show that Drosophila alter their dietary preference from yeast to plants when temperatures drop below 15°C and that the different lipids present in plants improve survival at ...
journal_title：Developmental cell
pub_type： 杂志文章
doi：10.1016/j.devcel.2018.05.028
更新日期：2018-09-24 00:00:00
abstract：:Optimal cell performance depends on cell size and the appropriate relative size, i.e., scaling, of the nucleus. How nuclear scaling is regulated and contributes to cell function is poorly understood, especially in skeletal muscle fibers, which are among the largest cells, containing hundreds of nuclei. Here, we presen...
journal_title：Developmental cell
pub_type： 杂志文章
doi：10.1016/j.devcel.2019.02.020
更新日期：2019-04-08 00:00:00
abstract：:DNA methylation on N6-adenine (6mA) has recently been found to be a potentially epigenetic mark in several unicellular and multicellular eukaryotes. However, its distribution patterns and potential functions in land plants, which are primary producers for most ecosystems, remain largely unknown. Here we report global ...
journal_title：Developmental cell
pub_type： 杂志文章
doi：10.1016/j.devcel.2018.03.012
更新日期：2018-05-07 00:00:00
abstract：:In this issue of Developmental Cell, Weavers and Skaer (2013) show that interplay between two opposing forces generated by tip cell attachment to muscles and migration of kink cells allows for the formation of the looped shape and positioning of renal tubules within the body of a fly larva. ...
journal_title：Developmental cell
pub_type： 评论,杂志文章
doi：10.1016/j.devcel.2013.10.021
更新日期：2013-11-11 00:00:00
abstract：:We show that Rap2, a member of the Ras GTPase family, positively regulates Activin/Nodal signaling activity by controlling the trafficking of its receptors. In the absence of ligand activation, Rap2 directs internalized Activin/Nodal receptors into a recycling pathway, thereby preventing their degradation and maintain...
journal_title：Developmental cell
pub_type： 杂志文章
doi：10.1016/j.devcel.2008.05.004
更新日期：2008-07-01 00:00:00
abstract：:Although autophagy is being pursued as a therapeutic target in clinical oncology trials, its effects on metastasis, the principal cause of cancer mortality, remain unclear. Here, we utilize mammary cancer models to temporally delete essential autophagy regulators during carcinoma progression. Though genetic ablation o...
journal_title：Developmental cell
pub_type： 杂志文章
doi：10.1016/j.devcel.2020.01.025
更新日期：2020-03-09 00:00:00
abstract：:The formation of epithelial tissues containing lumens requires not only the apical-basolateral polarization of cells, but also the coordinated orientation of this polarity such that the apical surfaces of neighboring cells all point toward the central lumen. Defects in extracellular matrix (ECM) signaling lead to inve...
journal_title：Developmental cell
pub_type： 杂志文章
doi：10.1016/j.devcel.2014.08.027
更新日期：2014-10-27 00:00:00
abstract：:The ureteric bud is an epithelial tube that undergoes branching morphogenesis to form the renal collecting system. Although development of a normal kidney depends on proper ureteric bud morphogenesis, the cellular events underlying this process remain obscure. Here, we used time-lapse microscopy together with several ...
journal_title：Developmental cell
pub_type： 杂志文章
doi：10.1016/j.devcel.2013.09.001
更新日期：2013-11-11 00:00:00
abstract：:The extracellular matrix (ECM) plays a major role in cancer progression through its increased deposition and alignment. In this issue of Developmental Cell, Fattet et al. reveal a pathway in which ECM stiffness promotes EPHA2/LYN complex activation, leading to TWIST1 nuclear localization and triggering EMT in breast c...
journal_title：Developmental cell
pub_type： 评论,杂志文章
doi：10.1016/j.devcel.2020.06.032
更新日期：2020-08-10 00:00:00
abstract：:Egg production declines with age in many species, a process linked with stem cell loss. Diet-dependent signaling has emerged as critical for stem cell maintenance during aging. Follicle stem cells (FSCs) in the Drosophila ovary are exquisitely responsive to diet-induced signals including Hedgehog (Hh) and insulin-IGF ...
journal_title：Developmental cell
pub_type： 杂志文章
doi：10.1016/j.devcel.2018.08.008
更新日期：2018-09-24 00:00:00
abstract：:Numerous signals drive the proliferative expansion of the distal endoderm and the underlying mesenchyme during lung branching morphogenesis, but little is known about how these signals are integrated. Here, we show by analysis of conditional double mutants that the two T-box transcription factor genes Tbx2 and Tbx3 ac...
journal_title：Developmental cell
pub_type： 杂志文章
doi：10.1016/j.devcel.2016.08.007
更新日期：2016-10-24 00:00:00
abstract：:What coordinates the internal leading and trailing edges in collectively migrating cells is largely unknown. In this issue of Developmental Cell, Barlan et al. (2017) delineate a Fat2/Lar planar signaling pathway at the basal, motile cell-cell contacts of Drosophila egg chamber follicle cells. ...
journal_title：Developmental cell
pub_type： 评论,杂志文章
doi：10.1016/j.devcel.2017.02.025
更新日期：2017-03-13 00:00:00
abstract：:The cytoskeleton is a major determinant of cell-shape changes that drive the formation of complex tissues during development. Important roles for actomyosin during tissue morphogenesis have been identified, but the role of the microtubule cytoskeleton is less clear. Here, we show that during tubulogenesis of the saliv...
journal_title：Developmental cell
pub_type： 杂志文章
doi：10.1016/j.devcel.2014.03.023
更新日期：2014-06-09 00:00:00
abstract：:The lymphatic system is crucial for fluid homeostasis, immune responses, and numerous pathological processes. However, the molecular mechanisms responsible for establishing the anatomical form of the lymphatic vascular network remain largely unknown. Here, we show that chemokine signaling provides critical guidance cu...
journal_title：Developmental cell
pub_type： 杂志文章
doi：10.1016/j.devcel.2012.01.011
更新日期：2012-04-17 00:00:00
abstract：:Tissues have a natural capacity to replace dying cells and to heal wounds. This ability resides in resident stem cells, which self-renew, preserve, and repair their tissue during homeostasis and following injury. The skin epidermis and its appendages are subjected to daily assaults from the external environment. A hig...
journal_title：Developmental cell
pub_type： 杂志文章,评审
doi：10.1016/j.devcel.2017.10.001
更新日期：2017-11-20 00:00:00
abstract：:Directional cell migration is critical for metazoan development. We define two molecular pathways that activate the Arp2/3 complex during neuroblast migration in Caenorhabditis elegans. The transmembrane protein MIG-13/Lrp12 is linked to the Arp2/3 nucleation-promoting factors WAVE or WASP through direct interactions ...
journal_title：Developmental cell
pub_type： 杂志文章
doi：10.1016/j.devcel.2016.09.029
更新日期：2016-10-24 00:00:00
abstract：:Drosophila proprioceptors (chordotonal organs) are structured as a linear array of four lineage-related cells: a neuron, a glial cell, and two accessory cells, called cap and ligament, between which the neuron is stretched. To function properly as stretch receptors, chordotonal organs must be stably anchored at both e...
journal_title：Developmental cell
pub_type： 杂志文章
doi：10.1016/j.devcel.2004.07.001
更新日期：2004-08-01 00:00:00
