Abstract：
:Nodal signaling induces the formation of the endoderm and mesoderm during gastrulation. Nodal expression persists until the definitive endoderm progenitor has completely formed, and disappears thereafter. A tightly regulated Nodal expression system is essential for the differentiation of embryonic stem (ES) cells into distinct tissue lineages. On this basis, we established an ES cell differentiation system with the tetracycline-regulated expression of Nodal. The upregulated Nodal signaling pathway and its downstream transcriptional targets induced the specification of ES cells into definitive endoderm and mesoderm derivatives, and the subsequent downregulation of Nodal signaling promoted further maturation of the gut tube both in vitro and in vivo. Sustained expression of the Nodal gene inhibited the maturation of the definitive endoderm owing to persistent Oct3 and/or Oct4 expression and teratoma formation. Furthermore, quantitative single cell analysis by flow cytometry using CXCR4, VEGFR2 and PDGFR-alpha indicated that this protocol for definitive endoderm and mesoderm differentiation is superior to any other available protocol. Our findings also indicated that the Nodal or Nodal-related molecules secreted from Nodal-expressing ES cells could cause genetically unmanipulated ES cells to induce the expression of the Nodal signaling pathway and its downstream targets, which consequently leads to the differentiation of the ES cells into definitive endoderm and mesoderm. Our differentiation system, using tightly regulated Nodal expression, enabled us to investigate the mechanism of ES cell differentiation into definitive endoderm or mesoderm derivatives. Our findings also demonstrate that Nodal-expressing ES cells might be a source of highly active proteins that could be used for developing endoderm or mesoderm tissues in regenerative medicine.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Takenaga M,Fukumoto M,Hori Ydoi
10.1242/jcs.004127subject
Has Abstractpub_date
2007-06-15 00:00:00pages
2078-90issue
Pt 12eissn
0021-9533issn
1477-9137pii
jcs.004127journal_volume
120pub_type
杂志文章abstract：:Polarization of the motile cell is associated with the formation of a distinct plasma membrane domain, the pseudopod, whose stabilization determines the directionality of cell movement. The rapid movement of cells over a substrate requires that an essential aspect of cell motility must be the supply of the necessary m...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：
更新日期：1999-06-01 00:00:00
abstract：:Axonemal precursor tubulin is the major protein component of the detergent-soluble membrane/matrix fraction of sea urchin embryonic cilia. Its unusual abundance may reflect the rapid turnover of these cilia, a process that is further documented here. However, whether during induced regeneration or normal turnover and ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1994-02-01 00:00:00
abstract：:Exocytosis and membrane recycling at the cytoproct (cell anus) of Tetrahymena pyriformis were studied using thin-section electron microscopy. Single cells were fixed at specific times relative to the elimination of the vacuole's contents--before elimination, at elimination, 3--5 s and 10--15 s following elimination. T...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1979-02-01 00:00:00
abstract：:We investigated the relative contributions of phagocytosis and plasma membrane transport to the uptake of amino acids and a protein (egg albumin) in amounts which allow Tetrahymena thermophila to grow and multiply. We used a mutant capable of indefinite growth without food vacuole formation (phagocytosis) and its wild...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1979-04-01 00:00:00
abstract：:Moving the nucleus to a specific position within the cell is an important event during many cell and developmental processes. Several different molecular mechanisms exist to position nuclei in various cell types. In this Commentary, we review the recent progress made in elucidating mechanisms of nuclear migration in a...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.179788
更新日期：2016-05-15 00:00:00
abstract：:It has been claimed repeatedly that gamma-tubulin is exclusively localized at the spindle poles in mitotic animal cells, where it plays a role in microtubule nucleation. In addition to this localization, we have observed a gamma-tubulin-specific staining of the mitotic spindle in several animal cells (human, kangaroo ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1994-10-01 00:00:00
abstract：:Syntaxin 1C (STX1C), produced by alternative splicing of the stx1A gene, is a soluble syntaxin lacking a SNARE domain and a transmembrane domain. It is unclear how soluble syntaxin can control intracellular membrane trafficking. We found that STX1C affected microtubule (MT) dynamics through its tubulin-binding domain ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.081943
更新日期：2012-02-15 00:00:00
abstract：:To evaluate the relative mobilities of cell surface glycoconjugates during myogenesis we have studied the redistribution of fluorescein-conjugated plant lectins on L6 rat myogenic cells. Previous experiments had demonstrated that the receptors for the lectins soybean agglutinin (SBA), wheat germ agglutinin, concanaval...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1986-07-01 00:00:00
abstract：:Four developmental stages of Rana pipiens, R. pipiens female X R. catesbeiana female, and R. pipiens female X R. esculenta male embryos were fixed in standard electron microscopic fixatives with or without 1% lanthanum nitrate (LN) added. Embryos fixed without LN were embedded and sectioned at 0-5 micrometer and stain...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1977-06-01 00:00:00
abstract：:In many epithelial cells, epidermal growth factor (EGF) augments the epithelial-mesenchymal transition (EMT) that occurs when cells are treated with transforming growth factor β (TGFβ). We demonstrate that this augmentation requires activation of SH2 domain-containing phosphatase-2 (SHP2; also known as PTPN11), a prot...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.169599
更新日期：2015-11-01 00:00:00
abstract：:The mitochondrial influx and efflux of Ca(2+) play a relevant role in cytosolic and mitochondrial Ca(2+) homeostasis, and contribute to the regulation of mitochondrial functions in neurons. The mitochondrial Na(+)/Ca(2+) exchanger, which was first postulated in 1974, has been primarily investigated only from a functio...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.129668
更新日期：2013-12-15 00:00:00
abstract：:We have identified a liver-regulating protein involved in cell contact-mediated regulation of Sertoli cell function by primary spermatocytes in rat testis. Liver-regulating protein was studied using monoclonal antibody L8 prepared from rat primitive biliary epithelial cells. This molecule was located in vivo at the in...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1995-03-01 00:00:00
abstract：:Members of the bimC family of kinesin related proteins (KRPs) play vital roles in the formation and function of the mitotic spindle. Although they share little amino acid homology outside the highly conserved microtubule motor domain, several family members do contain a 'bimC box', a sequence motif around a p34(cdc2) ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1998-04-01 00:00:00
abstract：:CENP-B binds to CENP-B boxes on centromeric satellite DNAs (known as alphoid DNA in humans). CENP-B maintains kinetochore function through interactions with CENP-A nucleosomes and CENP-C. CENP-B binding to transfected alphoid DNA can induce de novo CENP-A assembly, functional centromere and kinetochore formation, and ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.243303
更新日期：2020-08-11 00:00:00
abstract：:Recent biochemical and molecular approaches have begun to establish the protein interactions that lead to desmosome assembly. To determine whether these associations occur in native desmosomes we have performed ultrastructural localisation of specific domains of the major desmosomal components and have used the result...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1999-12-01 00:00:00
abstract：:When they are fixed with glutaraldehyde in the presence of calcium ions, the plasma membranes of Beroe giant smooth muscle fibres display micropapillae filled with an electron-dense deposit. After freeze-fracturing of fixed tissue, the micropapillae are still present, therefore their shape and size are determined duri...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1982-06-01 00:00:00
abstract：:New crystal structures of the kinesin motors differ from previously described motor-ADP atomic models, showing striking changes both in the switch I region near the nucleotide-binding cleft and in the switch II or 'relay' helix at the filament-binding face of the motor. The switch I region, present as a short helix fl...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：
更新日期：2002-01-01 00:00:00
abstract：:In the cytoplasm of chlorenchyma cells in primary Origanum dictamnus leaves, rectangular prism-like crystals occur, which, as shown by pepsin digestion, are proteinaceous. In sections they usually show either a square lattice or striations running parallel to the short or long axis. In both cases the interspacings are...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1983-11-01 00:00:00
abstract：:Ovarian follicles are the basic functional units of female reproduction in the mammalian ovary. We show here that the protein a disintegrin and metalloproteinase domain 10 (ADAM10), a cell surface sheddase, plays an indispensable role in controlling primordial follicle formation by regulating the recruitment of follic...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.184267
更新日期：2016-06-01 00:00:00
abstract：:Male infertility has become a worldwide health problem, but the etiologies of most cases are still unknown. SEPT12, a GTP-binding protein, is involved in male fertility. Two SEPT12 mutations (SEPT12(T89M) and SEPT12(D197N)) have been identified in infertile men who have a defective sperm annulus with a bent tail. The ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.158998
更新日期：2015-03-01 00:00:00
abstract：:Spatially separated apical and basolateral plasma membrane domains that have distinct functions and molecular compositions are a characteristic feature of epithelial cell polarity. The subapical compartment (SAC), also known as the common endosome (CE), where endocytic pathways from both surfaces merge, plays a crucia...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.01217
更新日期：2004-05-01 00:00:00
abstract：:Schizosaccharomyces pombe cells divide by medial fission throughout contraction of an actomyosin ring and deposition of a multilayered division septum that must be cleaved to release the two daughter cells. Although many studies have focused on the actomoysin ring and septum assembly, little information is available c...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.00377
更新日期：2003-05-01 00:00:00
abstract：:Recent studies suggest that cytochrome P450 (CYP) epoxygenase-derived epoxyeicosatrienoic acids (EETs) elicit cell proliferation and promote angiogenesis. The aim of this study was to determine the role of CYP 2C8/9-derived EETs in the process of angiogenesis under hypoxic conditions. In human endothelial cells, hypox...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.02674
更新日期：2005-12-01 00:00:00
abstract：:Ran is an abundant GTPase of the Ras superfamily that is highly conserved in eukaryotes. In interphase cells, Ran is mainly nuclear and thought to be predominantly GTP-bound, but it is also present in the cytoplasm, probably GDP-bound. This asymmetric distribution plays an important role in directing nucleocytoplasmic...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1999-07-01 00:00:00
abstract：:By passing a suspension of polymorphonuclear leucocytes through a parallel-plate chamber their adhesiveness can be assessed by scoring the number of cells trapped on the lower plate, and the fluid shear stress can be defined for a given flow rate. Since the adhesiveness of the cell at the instant of collision must exc...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1984-08-01 00:00:00
abstract：:MicroRNAs are known to play regulatory roles in gene expression associated with cancer development. We analyzed levels of the microRNA miR-24 in patients with breast carcinoma and found that miR-24 was higher in breast carcinoma samples than in benign breast tissues. We generated constructs expressing miR-24 and studi...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.118299
更新日期：2013-03-15 00:00:00
abstract：:Annexin A2 (AnxA2) is a multi-functional and -compartmental protein whose subcellular localisation and functions are tightly regulated by its post-translational modifications. AnxA2 and its Tyr23-phosphorylated form (pTyr23AnxA2) are involved in malignant cell transformation, metastasis and angiogenesis. Here, we show...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.173195
更新日期：2016-01-15 00:00:00
abstract：:Dispersion of neural crest cells and their ultimate regroupment into peripheral ganglia are associated with precisely coordinated regulations both in time and space of the expression and function of cell adhesion receptors. In particular, the disappearance of N-cadherin from the cell surface at the onset of migration ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1995-12-01 00:00:00
abstract：:Position-effect variegation results from mosaic silencing by chromosomal rearrangements juxtaposing euchromatin genes next to pericentric heterochromatin. An increase in the amounts of the heterochromatin-associated Su(var)3-7 and HP1 proteins augments silencing. Using the yeast two-hybrid protein interaction trap sys...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2000-12-01 00:00:00
abstract：:The position of the nucleus is regulated in different developmental stages and cellular events. During polarization, the nucleus moves away from the future leading edge and this movement is required for proper cell migration. Nuclear movement requires the LINC complex components nesprin-2G and SUN2, which form transme...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.087049
更新日期：2012-03-01 00:00:00
