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1.  In vivo reprogramming of pancreatic acinar cells to three islet endocrine subtypes 
eLife  2014;3:e01846.
Direct lineage conversion of adult cells is a promising approach for regenerative medicine. A major challenge of lineage conversion is to generate specific cell subtypes. The pancreatic islets contain three major hormone-secreting endocrine subtypes: insulin+ β-cells, glucagon+ α-cells, and somatostatin+ δ-cells. We previously reported that a combination of three transcription factors, Ngn3, Mafa, and Pdx1, directly reprograms pancreatic acinar cells to β-cells. We now show that acinar cells can be converted to δ-like and α-like cells by Ngn3 and Ngn3+Mafa respectively. Thus, three major islet endocrine subtypes can be derived by acinar reprogramming. Ngn3 promotes establishment of a generic endocrine state in acinar cells, and also promotes δ-specification in the absence of other factors. δ-specification is in turn suppressed by Mafa and Pdx1 during α- and β-cell induction. These studies identify a set of defined factors whose combinatorial actions reprogram acinar cells to distinct islet endocrine subtypes in vivo.
eLife digest
In mammals, the pancreas is responsible for controlling blood sugar by secreting insulin from specialized β-cells. Other cells in the pancreas, called δ-cells and α-cells, secrete other hormones to assist the β-cells. Diabetes is caused when this system breaks down: either the body attacks its own β-cells (type I diabetes), or the body stops responding properly to insulin (type II).
Type I diabetes is usually treated with insulin injections, but there is increasing interest in the possibility of replacing the defective β-cells instead. Building on previous work in which a fourth type of pancreatic cell, called an acinar cell, was reprogrammed to become a β-cell, Li et al. have now shown that the same technique can be used to produce α- and δ-cells as well. Just as the reprogrammed β-cells secreted insulin, like real β-cells, the reprogrammed α- and δ-cells also behaved like real α- and δ-cells.
The reprogramming technique relies on using a combination of three transcription factors—which are called Ngn3, Pdx1 and Mafa—to treat the acinar cells from mice. Previously, it was shown that using a combination of all three transcription factors reprogrammed the acinar cells to become β-cells. Now, Li et al. show that the Ngn3 transcription factor on its own appears to suppress certain genes that are usually expressed in acinar cells, and goes on to cause the acinar cells to become δ-cells. However, a combination of Ngn3 and Mafa produces a mixture of α- and δ-cells. The next challenge is to adapt this reprogramming technique to generate different types of hormone secreting cells from human tissue sources in order to explore its therapeutic potential.
PMCID: PMC3977343  PMID: 24714494
pancreatic endocrine cells; direct lineage conversion; in vivo reprogramming; acinar to endocrine conversion; islet delta, alpha, beta cells; mouse
2.  Podocalyxin Is a Glycoprotein Ligand of the Human Pluripotent Stem Cell-Specific Probe rBC2LCN 
This study demonstrates that podocalyxin, a heavily glycosylated type 1 transmembrane protein, is a glycoprotein ligand of rBC2LCN on human induced pluripotent stem (iPS) cells and embryonic stem (ES) cells. When analyzed by DNA microarray, podocalyxin was found to be highly expressed in both iPS cells and ES cells. The carbohydrate antigens of rBC2LCN are expressed on O-glycans of podocalyxin, since alkaline hydrolysis greatly reduced the binding of rBC2LCN to human iPS cells and ES cells. rBC2LCN bound to an O-glycan carrying H type 3 epitope structure isolated from iPS cells, suggesting that H type 3 is a novel pluripotency glycan marker.
In comprehensive glycome analysis with a high-density lectin microarray, we have previously shown that the recombinant N-terminal domain of the lectin BC2L-C from Burkholderia cenocepacia (rBC2LCN) binds exclusively to undifferentiated human induced pluripotent stem (iPS) cells and embryonic stem (ES) cells but not to differentiated somatic cells. Here we demonstrate that podocalyxin, a heavily glycosylated type 1 transmembrane protein, is a glycoprotein ligand of rBC2LCN on human iPS cells and ES cells. When analyzed by DNA microarray, podocalyxin was found to be highly expressed in both iPS cells and ES cells. Western and lectin blotting revealed that rBC2LCN binds to podocalyxin with a high molecular weight of more than 240 kDa in undifferentiated iPS cells of six different origins and four ES cell lines, but no binding was observed in either differentiated mouse feeder cells or somatic cells. The specific binding of rBC2LCN to podocalyxin prepared from a large set of iPS cells (138 types) and ES cells (15 types) was also confirmed using a high-throughput antibody-overlay lectin microarray. Alkaline digestion greatly reduced the binding of rBC2LCN to podocalyxin, indicating that the major glycan ligands of rBC2LCN are presented on O-glycans. Furthermore, rBC2LCN was found to exhibit significant affinity to a branched O-glycan comprising an H type 3 structure (Ka, 2.5 × 104 M−1) prepared from human 201B7 iPS cells, indicating that H type 3 is a most probable potential pluripotency marker. We conclude that podocalyxin is a glycoprotein ligand of rBC2LCN on human iPS cells and ES cells.
PMCID: PMC3659831  PMID: 23526252
Differentiation antigens; Embryonic stem cells; Glycosaminoglycan; Induced pluripotent stem cells; Microarray; Reprogramming
3.  Text mining meets workflow: linking U-Compare with Taverna 
Bioinformatics  2010;26(19):2486-2487.
Summary: Text mining from the biomedical literature is of increasing importance, yet it is not easy for the bioinformatics community to create and run text mining workflows due to the lack of accessibility and interoperability of the text mining resources. The U-Compare system provides a wide range of bio text mining resources in a highly interoperable workflow environment where workflows can very easily be created, executed, evaluated and visualized without coding. We have linked U-Compare to Taverna, a generic workflow system, to expose text mining functionality to the bioinformatics community.
Supplementary information: Supplementary data are available at Bioinformatics online.
PMCID: PMC2944208  PMID: 20709690

Results 1-3 (3)