Abstract:
:We have characterised the transdifferentiation of human HepG2 (hepatoma) cells to pancreatic cells following introduction of an activated version of the pancreatic transcription factor Pdx1 (XlHbox8-VP16). The following questions are addressed: (1) are all types of pancreatic cells produced? (2) is the requirement for expression of the transgene temporary or permanent? (3) are the transdifferentiated beta-cells responsive to physiological stimuli? The results showed that both pancreatic exocrine cells (by detection of amylase protein), and endocrine cells (by detecting insulin, glucagon and somatostatin proteins) are induced after XlHbox8VP16 transfection. Moreover, the hepatic phenotype becomes suppressed during transdifferentiation of hepatocytes to pancreatic cells. Requirement for the transgene is only temporary and it is no longer required once the pancreatic differentiation program is activated. Finally, we provided results to suggest that the transdifferentiated cells are functional by detecting: (1) functional markers for pancreatic beta-cells including prohormone convertase 1/3 (PC1/3), insulin C-peptide and glucagon-like peptide 1 receptor (GLP-1R), (2) increased insulin mRNA expression after treatment of cells with GLP-1 and betacellulin, physiological stimuli that regulate pancreatic function and (3) elevated insulin secretion after glucose challenge. The transdifferentiation of hepatic to pancreatic cells represents one possible source of beta-cells for human islet transplantation and this study shows that such a transdifferentiation can be achieved in vitro.
journal_name
Mech Devjournal_title
Mechanisms of developmentauthors
Li WC,Horb ME,Tosh D,Slack JMdoi
10.1016/j.mod.2005.01.001subject
Has Abstractpub_date
2005-06-01 00:00:00pages
835-47issue
6eissn
0925-4773issn
1872-6356pii
S0925-4773(05)00002-Xjournal_volume
122pub_type
杂志文章abstract::Formation of tubular structures from an epithelial tissue is a process common to many morphogenetic events during organogenesis. We report here new data concerning the expression pattern of the vHNF1/HNF1beta gene during this process in the mouse. vHNF1 (variant Hepatocyte Nuclear Factor 1) is a member of the HNF1 hom...
journal_title:Mechanisms of development
pub_type: 杂志文章
doi:10.1016/s0925-4773(99)00221-x
更新日期:1999-12-01 00:00:00
abstract::Commissureless (Comm) is a novel transmembrane molecule necessary both for commissural axons to cross the midline of the Drosophila central nervous system and normal synaptogenesis. Comm is able to reduce cell surface levels of Roundabout (Robo), a receptor for the midline repellent Slit, on commissural axons and unkn...
journal_title:Mechanisms of development
pub_type: 杂志文章
doi:10.1016/s0925-4773(03)00179-5
更新日期:2003-09-01 00:00:00
abstract::The fork head domain-containing gene family (Fox) comprises over 20 members in mammals and is defined by a conserved 110 amino-acid motif containing a winged helix structure DNA-binding domain. The members of this gene family have been implicated as key regulators of embryogenesis, cell cycling, cell lineage restricti...
journal_title:Mechanisms of development
pub_type: 杂志文章
doi:10.1016/s0925-4773(02)00220-4
更新日期:2002-10-01 00:00:00
abstract::The Extramacrochaetae (emc) gene encodes a transcription factor with an HLH domain without the basic region involved in interaction with DNA present in other proteins that have this domain. EMC forms heterodimers with bHLH proteins preventing their binding to DNA, acting as a negative regulator. The function of emc is...
journal_title:Mechanisms of development
pub_type: 杂志文章
doi:10.1016/s0925-4773(98)00198-1
更新日期:1999-02-01 00:00:00
abstract::The gene crumbs (crb) of Drosophila encodes a transmembrane protein with 30 EGF-like and four laminin A G-domain-like repeats in its extracellular domain. Loss-of-function mutations lead to severe disorganization and degeneration of ectodermally derived embryonic epithelia. In embryos homozygous for crb8F105, an amorp...
journal_title:Mechanisms of development
pub_type: 杂志文章
doi:10.1016/0925-4773(93)90066-7
更新日期:1993-12-01 00:00:00
abstract::Five chick homeodomain proteins (CHOXs), CHOX-1.7, -1.1, -1.4, -4.2 and -2.6, had different transcription-regulating activities in a chick cultured cell line, LMH. In particular, CHOX-1.7 highly activated transcription when NP6 was used as the target site whereas CHOX-1.4 did not. This was mainly due to differences in...
journal_title:Mechanisms of development
pub_type: 杂志文章
doi:10.1016/0925-4773(92)90012-9
更新日期:1992-03-01 00:00:00
abstract::The normal embryogenesis of marine animals is typically confined to a species-specific range of temperatures. Within that temperature range development results in a consistent, or canalized, phenotype, whereas above and below the range abnormal phenotypes are produced. This study reveals a high temperature threshold, ...
journal_title:Mechanisms of development
pub_type: 杂志文章
doi:10.1016/j.mod.2019.04.002
更新日期:2019-06-01 00:00:00
abstract::In mouse Otx2 plays essential roles in anterior-posterior axis formation and head development in anterior visceral endoderm and anterior mesendoderm. The Otx2 expression in these sites is regulated by VE and CM enhancers at the 5' proximal to the translation start site, and we proposed that these enhancers would have ...
journal_title:Mechanisms of development
pub_type: 杂志文章
doi:10.1016/j.mod.2011.11.001
更新日期:2012-01-01 00:00:00
abstract::NK-2 class homeobox genes are candidate patterning and lineage regulators in diverse organisms. We report here the embryonic expression pattern of murine member, Nkx2-6. In keeping with its vertebrate relatives, Nkx2-6 was transcribed in ventrolateral embryonic structures. Expression was first detected at E8.0 in endo...
journal_title:Mechanisms of development
pub_type: 杂志文章
doi:10.1016/s0925-4773(98)00037-9
更新日期:1998-04-01 00:00:00
abstract::In C. elegans development, unfavorable growth conditions lead a larva to an arrested and enduring form called a dauer. To elucidate components upstream of DAF-7/TGF-beta in this control pathway, we isolated a mutant that was defective in daf-7 promoter::gfp reporter expression and showed an arrested (dauer-constitutiv...
journal_title:Mechanisms of development
pub_type: 杂志文章
doi:10.1016/s0925-4773(01)00507-x
更新日期:2001-11-01 00:00:00
abstract::The Bar homeobox genes play an essential role during nervous system and eye development in Drosophila. We isolated a medaka Bar gene closely related to the Drosophila and mammalian Bar genes. In the medaka embryo, OlBar is expressed from gastrula stages onwards, in a region demarcating the presumptive prosencephalic-m...
journal_title:Mechanisms of development
pub_type: 杂志文章
doi:10.1016/s0925-4773(02)00054-0
更新日期:2002-06-01 00:00:00
abstract::Avian neural crest cells migrate on precise pathways to their target areas where they form a wide variety of cellular derivatives, including neurons, glia, pigment cells and skeletal components. In one portion of their pathway, trunk neural crest cells navigate in the somitic mesoderm in a segmental fashion, invading ...
journal_title:Mechanisms of development
pub_type: 杂志文章,评审
doi:10.1016/s0925-4773(01)00395-1
更新日期:2001-07-01 00:00:00
abstract::We describe the structural organization of a gene, termed XFDL 141/156, that is transiently activated during early Xenopus development. XFDL 141/156 is first transcribed at the midblastula transition (MBT) and during early gastrulation events. A roughly 200 nucleotide fragment immediately 5' to the transcription start...
journal_title:Mechanisms of development
pub_type: 杂志文章
doi:10.1016/s0925-4773(97)00034-8
更新日期:1997-04-01 00:00:00
abstract::HNF1 (Hepatic Nuclear Factor 1) and vHNF1 are transcriptional regulators containing a highly divergent homeodomain. The first was initially found in liver nuclear extracts and is crucial for the transcription of albumin and many other hepatocyte specific genes, while the second was found in dedifferentiated hepatoma c...
journal_title:Mechanisms of development
pub_type: 杂志文章
doi:10.1016/0925-4773(91)90071-d
更新日期:1991-12-01 00:00:00
abstract::Proper metazoan mesoderm development requires the function of a basic helix-loop-helix (bHLH) transcription factor, Twist. Twist-containing dimers regulate the expression of target genes by binding to E box promoter elements containing the site CANNTG. In Caenorhabditis elegans, CeTwist functions in a subset of mesode...
journal_title:Mechanisms of development
pub_type: 杂志文章
doi:10.1016/j.mod.2007.01.005
更新日期:2007-05-01 00:00:00
abstract::The diencephalon is the caudal part of the developing forebrain that gives rise to the epithalamus, thalamus, hypothalamus and retina. The mature diencephalon is functionally and anatomically parceled into well-defined nuclei. In an effort to understand how this region of the brain develops we examined the expression ...
journal_title:Mechanisms of development
pub_type: 杂志文章
doi:10.1016/s0925-4773(02)00091-6
更新日期:2002-07-01 00:00:00
abstract::The neural crest (NC) is one of the most fascinating structures during embryonic development. Unique to vertebrate embryos, these cells give rise to important components of the craniofacial skeleton, such as the jaws and skull, as well as melanocytes and ganglia of the peripheral nervous system. Worldwide, several gro...
journal_title:Mechanisms of development
pub_type: 杂志文章,评审
doi:10.1016/j.mod.2018.07.009
更新日期:2018-10-01 00:00:00
abstract::ADAM19 is a member of the meltrin subfamily of ADAM metalloproteases. In Xenopus, ADAM19 is present as a maternal transcript. Zygotic expression starts during gastrulation and is apparent in the dorsal blastopore lip. ADAM19 expression through neurulation and tailbud formation becomes enriched in dorsal structures suc...
journal_title:Mechanisms of development
pub_type: 杂志文章
doi:10.1016/j.mod.2008.10.010
更新日期:2009-03-01 00:00:00
abstract::In a screen for receptor tyrosine kinase genes regionally expressed in the developing hindbrain, we cloned and characterised the chicken ret gene. Data derived from studies of congenital human disease and from disruption of murine ret have demonstrated roles for ret in development of the kidney and enteric nervous sys...
journal_title:Mechanisms of development
pub_type: 杂志文章
doi:10.1016/0925-4773(95)00449-1
更新日期:1995-11-01 00:00:00
abstract::There has been rapid progress recently in the identification of signalling pathways regulating tooth development. It has become apparent that signalling networks involved in Drosophila development and development of mammalian organs such as the limb are also used in tooth development. Teeth are epithelial appendages f...
journal_title:Mechanisms of development
pub_type: 杂志文章,评审
doi:10.1016/s0925-4773(97)00115-9
更新日期:1997-10-01 00:00:00
abstract::A pool of beta 1-integrin, ready to be inserted into the cleavage membranes, is present in the cytoplasm of the Xenopus egg, while its plasma membrane is devoid of this membrane protein (Gawantka et al., 1992). The underlying mechanisms that lead to this specific pattern of beta 1-integrin distribution in the egg have...
journal_title:Mechanisms of development
pub_type: 杂志文章
doi:10.1016/0925-4773(93)90100-c
更新日期:1993-07-01 00:00:00
abstract::The Cbl family of proteins act as E3 ubiquitin-protein ligases and have been associated with the down regulation of a variety of receptor tyrosine kinases. Cbl proteins associate with many different cell signalling molecules suggesting that they may have functions outside of the RING finger-mediated ubiquitin ligase a...
journal_title:Mechanisms of development
pub_type: 杂志文章
doi:10.1016/s0925-4773(01)00292-1
更新日期:2001-04-01 00:00:00
abstract::In situ hybridization analysis of Xenopus laevis embryos reveals that mRNA encoding the platelet-derived growth factor alpha receptor (PDGFR alpha) is expressed in cephalic neural crest masses prior to migration from the future neural tube and during their migration into the visceral arches. The analysis of fluorescen...
journal_title:Mechanisms of development
pub_type: 杂志文章
doi:10.1016/0925-4773(94)90057-4
更新日期:1994-12-01 00:00:00
abstract::During vertebrate eye development, the expression of the homeobox gene Six6 is restricted to the neural retina and is initiated later than Rx and Pax6 in the presumptive retina field. We show here that overexpression of mouse Six6 in Xenopus embryos can induce transformation of competent tissue of the anterior neural ...
journal_title:Mechanisms of development
pub_type: 杂志文章
doi:10.1016/s0925-4773(00)00271-9
更新日期:2000-05-01 00:00:00
abstract::Mutations in the CFTR gene cause cystic fibrosis (CF) with myocardial dysfunction. However, it remains unknown whether CF-related heart disease is a secondary effect of pulmonary disease, or an intrinsic primary defect in the heart. Here, we used zebrafish, which lack lung tissue, to investigate the role of CFTR in ca...
journal_title:Mechanisms of development
pub_type: 杂志文章
doi:10.1016/j.mod.2020.103627
更新日期:2020-09-01 00:00:00
abstract::We have identified a Drosophila gene encoding a putative receptor tyrosine kinase by screening a genomic DNA library with a DNA probe for a Drosophila homolog of fibroblast growth factor receptors. The newly isolated gene codes for a transmembrane protein most similar in sequence to a mammalian proto-oncogene ret; thu...
journal_title:Mechanisms of development
pub_type: 杂志文章
doi:10.1016/0925-4773(94)90027-2
更新日期:1994-02-01 00:00:00
abstract::Recent studies have shown that aberrantly expressed gastrin-releasing peptide (GRP) and its receptor (GRP-R) critically regulate tumor cell differentiation in colon cancers developing in humans and mice. This finding suggested that the ability of GRP/GRP-R to promote a well-differentiated phenotype in colon cancer mig...
journal_title:Mechanisms of development
pub_type: 杂志文章
doi:10.1016/s0925-4773(02)00032-1
更新日期:2002-05-01 00:00:00
abstract::We performed a systematic screen for mutations affecting the trajectory of axons visualized by immunohistochemical staining of Medaka embryos with anti-acetylated tubulin antibody. Among the mutations identified, yanagi (yan) and kazura (kaz) mutations caused specific defects in projection of the posterior lateral lin...
journal_title:Mechanisms of development
pub_type: 杂志文章
doi:10.1016/j.mod.2004.03.032
更新日期:2004-07-01 00:00:00
abstract::Tribolium castaneum is a well-characterised model insect, whose short germ-band mode of embryonic development is characteristic of many insect species and differs from the exhaustively studied Drosophila. Mechanisms of early neurogenesis, however, show significant conservation with Drosophila, as a characteristic patt...
journal_title:Mechanisms of development
pub_type: 杂志文章
doi:10.1016/j.mod.2013.02.003
更新日期:2013-04-01 00:00:00
abstract::It is now well established that apoptosis is induced in response to mechanical strain. Indeed, increasing compressive forces induces apoptosis in confined spheroids of tumour cells, whereas releasing stress reduces apoptosis in spheroids cultivated in free suspension (Cheng et al., 2009). Apoptosis can also be induced...
journal_title:Mechanisms of development
pub_type: 杂志文章,评审
doi:10.1016/j.mod.2016.10.001
更新日期:2017-04-01 00:00:00