Pdx1 protein induces human embryonic stem cells into the pancreatic endocrine lineage

Liang, Qing; Mo, Zheng-ying; Li, Xue Feng; Wang, Xiao Xun; Li, Rui Ming

doi:10.1002/cbin.10001

Cited by 9 publications

(3 citation statements)

References 32 publications

(47 reference statements)

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“…Given the high efficiency of functional PTD-mediated cargo delivery by P21 enhancement, we reasoned that GET technology might also be used to redirect pluripotent cells toward differentiated cell fates, using the transduction to deliver recombinant transcription factors (24)(25)(26).…”

Section: Get Requires the Presence Of Trypsin-sensitive And Detergentmentioning

confidence: 99%

Highly efficient delivery of functional cargoes by the synergistic effect of GAG binding motifs and cell-penetrating peptides

Dixon

Osman

Morris

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

128

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Protein transduction domains (PTDs) are powerful nongenetic tools that allow intracellular delivery of conjugated cargoes to modify cell behavior. Their use in biomedicine has been hampered by inefficient delivery to nuclear and cytoplasmic targets. Here we overcame this deficiency by developing a series of novel fusion proteins that couple a membrane-docking peptide to heparan sulfate glycosaminoglycans (GAGs) with a PTD. We showed that this GET (GAG-binding enhanced transduction) system could deliver enzymes (Cre, neomycin phosphotransferase), transcription factors (NANOG, MYOD), antibodies, native proteins (cytochrome C), magnetic nanoparticles (MNPs), and nucleic acids [plasmid (p)DNA, modified (mod)RNA, and small inhibitory RNA] at efficiencies of up to two orders of magnitude higher than previously reported in cell types considered hard to transduce, such as mouse embryonic stem cells (mESCs), human ESCs (hESCs), and induced pluripotent stem cells (hiPSCs). This technology represents an efficient strategy for controlling cell labeling and directing cell fate or behavior that has broad applicability for basic research, disease modeling, and clinical application.

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Section: Get Requires the Presence Of Trypsin-sensitive And Detergentmentioning

confidence: 99%

Highly efficient delivery of functional cargoes by the synergistic effect of GAG binding motifs and cell-penetrating peptides

Dixon

Osman

Morris

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

128

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show abstract

“…Moreover, Pdx1 is believed to act as a potent glucose-responsive transcriptional activator in insulin gene expression [33]. Pancreatic islets did not develop in homozygous Pdx1-depleted mice, and human fetus with Pdx1 mutation also presented a similar phenotype [34]. During embryonic development, Ngn3-positive cells were decreased by about 20 % in the pancreas of mice restricted by energy or protein supply compared with the control mice; Pdx1positive cells were decreased by 47 % [35].…”

Section: Sga + Nsmentioning

confidence: 99%

Early Growth Hormone Intervention Improves Glucose Metabolism in Adult Rats Born Small for Gestational Age

Wang

Zhu

Chen

et al. 2018

Exp Clin Endocrinol Diabetes

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Background Small for gestational age (SGA) due to intrauterine malnourishment is closely related to metabolic syndrome and type 2 diabetes mellitus. Growth Hormone (GH) treatment has been demonstrated to influence metabolic parameters and islet function of SGA individuals. The present study demonstrates the effects of early GH treatment on glucose tolerance and expression of pancreatic duodenal homeobox 1 (Pdx1) of SGA rats during adulthood. Methods SGA rat model was induced by restricting food intake during pregnancy. GH or normal saline was administered during postnatal days 21–35 of SGA rats and appropriate for gestational age (AGA) rats, respectively. Results In early adulthood (postnatal day 70), as compared to AGA rats, SGA rats showed: (1) decreased body weight; (2) increased postprandial blood glucose; and (3) down-regulated Pdx1 with increased histone deacetylase (HDAC) and down-regulated histone H3-lysine 4 methyltransferase SET7/9. Exogenous GH administration led to a restoration of body weight and normalized glucose tolerance due to an enhanced Pdx1 expression, accompanied by decreased HDAC and up-regulated SET7/9 in SGA rats in early adulthood. Conclusion Our results demonstrate positive effects on glucose metabolism by an early and short GH treatment in SGA adulthood.

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“…The first use of a HP in a "therapeutic context" was reported in 2003 with the ability of HoxB4 to enhance the proliferation of hematopoietic precursors [59]. In the same context of progenitor proliferation or differentiation one can cite the recent work on Pdx1 that drives human Embryonic stem cells into insulin producing cells [60]. …”

Section: Therapeutic Proteinsmentioning

confidence: 99%

Signaling with Homeoprotein Transcription Factors in Development and Throughout Adulthood

Prochiantz

2013

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The concept of homeoprotein transduction as a novel signaling pathway has dramatically evolved since it was first proposed in 1991. It is now well established in several biological systems from plants to mammals. In this review, the different steps that have led to this unexpected observation are recalled and the developmental and physiological models that have allowed us (and a few others) to consolidate the original hypothesis are described. Because homeoprotein signaling is active in plants and animals it is proposed that it has predated the separation between animals and plants and is thus very ancient. This may explain why the basic phenomenon of homeoprotein transduction is so minimalist, requiring no specific receptors or transduction pathways beside those offered by mitochondria, organelles present in all eukaryotic cells. Indeed complexity has been added in the course of evolution and the conservation of homeoprotein transduction is discussed in the context of its synergy with bona fide signaling mechanism that may have added robustness to this primitive cell communication device. The same synergy possibly explains why homeoprotein signaling is important both in embryonic development and in adult functions fulfilled by signaling entities (e.g. growth factors) themselves active throughout development and in the adult. The cell biological mechanism of homeoprotein transfer is also discussed. Although it is clear that many questions are still in want of precise answers, it appears that the sequences responsible both for secretion and internalization are in the DNA-binding domain and very highly conserved among most homeoproteins. On this basis, it is proposed that this signaling pathway is likely to imply as many as 200 proteins that participate in a myriad of developmental and physiological pathways.

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Pdx1 protein induces human embryonic stem cells into the pancreatic endocrine lineage

Cited by 9 publications

References 32 publications

Highly efficient delivery of functional cargoes by the synergistic effect of GAG binding motifs and cell-penetrating peptides

Highly efficient delivery of functional cargoes by the synergistic effect of GAG binding motifs and cell-penetrating peptides

Early Growth Hormone Intervention Improves Glucose Metabolism in Adult Rats Born Small for Gestational Age

Signaling with Homeoprotein Transcription Factors in Development and Throughout Adulthood

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