Sonic Hedgehog and Other Soluble Factors from Differentiating Embryoid Bodies Inhibit Pancreas Development

Mfopou, Josué Kunjom; Groote, Véronique De; Xu, Xiabo; Heimberg, Harry; Bouwens, Luc

doi:10.1634/stemcells.2006-0720

Cited by 41 publications

(38 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fig. 2; Kubo et al 2004, Jiang et al 2007, Mfopou et al 2007. Given the fact that thyroid follicular cells also arise from the endoderm during vertebrate development, it is likely that similar strategies could be used to stimulate their differentiation from human ES cells.…”

Section: Thomas Et Al: Thyroid Stem Cellsmentioning

confidence: 99%

Thyroid stem cells: lessons from normal development and thyroid cancer

Thomas

Friedman²,

Lin

2008

Endocrine Related Cancer

View full text Add to dashboard Cite

Ongoing advances in stem cell research have opened new avenues for therapy for many human disorders. Until recently, however, thyroid stem cells have been relatively understudied. Here, we review what is known about thyroid stem cells and explore their utility as models of normal and malignant biological development. We also discuss the cellular origin of thyroid cancer stem cells and explore the clinical implications of cancer stem cells in the thyroid gland. Since thyroid cancer is the most common form of endocrine cancer and that thyroid hormone is needed for the growth and metabolism of each cell in the body, understanding the molecular and the cellular aspects of thyroid stem cell biology will ultimately provide insights into mechanisms underlying human disease.

show abstract

Section: Thomas Et Al: Thyroid Stem Cellsmentioning

confidence: 99%

Thyroid stem cells: lessons from normal development and thyroid cancer

Thomas

Friedman²,

Lin

2008

Endocrine Related Cancer

View full text Add to dashboard Cite

show abstract

“…Culture of mouse embryonic stem cells and isolation of conditioned medium Mouse embryonic stem cells (E14 from 129Ola mice) were maintained undifferentiated on mitomycin C-inactivated mouse embryonic fibroblasts in knockout DMEM (Invitrogen) supplemented with 10 ng/ml LIF as previously described [25,26]. Differentiation was initiated in suspension by embryoid body formation in DMEM supplemented with 10% FBS and antibiotics.…”

Section: Methodsmentioning

confidence: 99%

“…To this end, we made use of the well-established alkaloid, 3-keto-N-(aminoethyl-aminocaproyl-dihydrocinnamoyl)-cyclopamine (KAAD-cyclopamine), to inhibit hedgehog signalling. To activate the pathway, we used conditioned medium from embryoid bodies, which was previously shown to inhibit ex vivo differentiation of mouse embryonic pancreas in a hedgehog-dependent manner [25,26].…”

Section: Introductionmentioning

confidence: 99%

Hedgehog signals inhibit postnatal beta cell neogenesis from adult rat exocrine pancreas in vitro

2012

View full text Add to dashboard Cite

Aims/hypothesis Transdifferentiation of pancreatic exocrine cells into insulin-producing beta cells may represent an important alternative to islets required for diabetes cell therapy. Rat pancreatic acinar cells are known to transdifferentiate into functional beta cells, with recapitulation of several pancreas developmental features. Considering the inhibitory functions of hedgehog signalling in early and mid-stage pancreatic development, we questioned whether it also operates in transdifferentiating acinar cells and whether its modulation would influence postnatal beta cell neogenesis in vitro. Methods Rat exocrine cells were precultured in suspension for 4 days and then incubated with EGF and leukaemia inhibitory factor (LIF) for 72 h. The hedgehog signalling pathway was modulated during this, and its effects analysed by RT-PCR, immunocytochemistry and western blot. Results Our data indicate induction of Dhh and Ihh, but not Shh, expression during acinar cell culture, resulting in activation of hedgehog targets (Ptc1, Gli1). Exposure of the metaplastic cells to EGF and LIF induced beta cell differentiation without affecting endogenous hedgehog activity. Whereas blocking endogenous hedgehog only slightly increased beta cell neogenesis, exposure to embryoid body-conditioned medium activated hedgehog signalling as well as other pathways such as Notch, resulting in severe blockade of beta cell neogenesis. Interestingly, this effect was partially rescued by treatment with the hedgehog inhibitor, 3-keto-N-(aminoethylaminocaproyl-dihydrocinnamoyl)-cyclopamine (KAADcyclopamine), alone. Conclusions/interpretation We report here Dhh/Ihh-dependent activation of hedgehog targets during pancreatic exocrine cell metaplasia in vitro and a persistent inhibitory function of hedgehog signalling in a model of postnatal beta cell differentiation.

show abstract

“…Recently, the Davies laboratory demonstrated the TSH-independent induction of thyroid endoderm from ES cells by activin A. Activin A is a member of the TGFβ superfamily, which has been shown to be critical to the regulation of endoderm formation in vitro and in vivo (D'Amour et al, 2005;Kubo et al, 2004;Mfopou et al, 2007;Ninomiya et al, 1999;Rippon et al, 2006). Adding activin A to cultures of embryoid bodies markedly increased endodermal markers, including Gata4, CXCR4 and Foxa2 and -fetoprotein.…”

Section: Tsh-independent Induction Of Thyrocytes From Mouse Es Cellsmentioning

confidence: 99%