Pancreas Extract

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Esmaeil Ebrahimie - One of the best experts on this subject based on the ideXlab platform.

  • Induction of pancreatic β cell gene expression in mesenchymal stem cells.
    Cell biology international, 2016
    Co-Authors: Zahra Mehrfarjam, Fariba Esmaeili, Leila Shabani, Esmaeil Ebrahimie
    Abstract:

    Transdifferentiattion potential of mesenchymal stem cells (MSCs) into insulin-producing cells (IPCs) has been suggested recently. In our recent works, we demonstrated the high performance of mouse neonate Pancreas Extract (MPE) in the production of functional IPCs from carcinoma stem cells. In this study, MPE was used to generate IPCs from MSCs without any genetic manipulation. To this end, bone marrow MSCs were isolated and characterized. In order to differentiate, MSCs were induced by selection of nestin-expressing cells and treatment with 100 μg/mL MPE. Morphological features of the differenti-ated cells were confirmed by dithizone staining. Immunoreactivity to insulin receptor beta, proinsulin, insulin, and C-peptide was observed by immunoflourescence. We also quantified glucose-dependent insulin production and secretion by ELISA. Real-time PCR indicated the expressions of β cell-related genes, PDX-1, INS1, INS2, EP300, and CREB1, in IPC cells. Possible pathways governed by CREB1, EP300, and PDX-1 transcription factors in differentiation of MSCs to IPCs were determined based on Gene Set Enrichment (GSE) approach at P = 0.05. Pathway discovery highlighted the negative regulatory effects of MIR124-2, HDAC5 protein, REST, and NR0B2 transcription factors on expression of CREB1, EP300, and PDX-1 and inhabitation of IPC differentiations. In contrast, a crosstalk between FOXA2 and TCF7L2 transcription factors, DNA-PK complex, KAT2B protein positively interacting with PDX-1, CREB1, EP300 resulted in the induction of IPC and following insulin production. In conclusion, we report an efficient, simple, and easy method for production of functional IPCs from MSCs by MPE treatment.

  • Induction of pancreatic b cell gene expression in mesenchymal stem cells
    2016
    Co-Authors: Zahra Mehrfarjam, Fariba Esmaeili, Leila Shabani, Esmaeil Ebrahimie
    Abstract:

    Transdifferentiattion potential of mesenchymal stem cells (MSCs) into insulin-producing cells (IPCs) has been suggestedrecently. In our recent works, we demonstrated the high performance of mouse neonate Pancreas Extract (MPE) in theproduction of functional IPCs fromcarcinoma stemcells. In this study, MPE was used to generate IPCs from MSCs without anygenetic manipulation. To this end, bone marrow MSCs were isolated and characterized. In order to differentiate, MSCs wereinduced by selection of nestin-expressing cells and treatment with 100mg/mLMPE. Morphological features of the differentiatedcells were confirmed by dithizone staining. Immunoreactivity to insulin receptor beta, proinsulin, insulin, and C-peptide wasobserved by immunoflourescence. We also quantified glucose-dependent insulin production and secretion by ELISA. Real-timePCR indicated the expressions of b cell-related genes, PDX-1, INS1, INS2, EP300, and CREB1, in IPC cells. Possible pathwaysgoverned by CREB1, EP300, and PDX-1 transcription factors in differentiation ofMSCs to IPCswere determined based on GeneSet Enrichment (GSE) approach at P¼0.05. Pathway discovery highlighted the negative regulatory effects of MIR124-2,HDAC5protein, REST, and NR0B2 transcription factors on expression of CREB1, EP300, and PDX-1 and inhabitation of IPCdifferentiations. In contrast, a crosstalk between FOXA2 and TCF7L2 transcription factors, DNA-PK complex, KAT2B proteinpositively interacting with PDX-1, CREB1, EP300 resulted in the induction of IPC and following insulin production. Inconclusion, we report an efficient, simple, and easy method for production of functional IPCs from MSCs by MPE treatment.Keywords: insulin-producing cells; mesenchymal stem cells; nestin-positive cells; Pancreas Extract; stem cell differentiation

  • Efficient and simple production of insulin-producing cells from embryonal carcinoma stem cells using mouse neonate Pancreas Extract, as a natural inducer.
    PloS one, 2014
    Co-Authors: Marzieh Ebrahimie, Fariba Esmaeili, Fariba Houshmand, Somayeh Cheraghi, Leila Shabani, Esmaeil Ebrahimie
    Abstract:

    An attractive approach to replace the destroyed insulin-producing cells (IPCs) is the generation of functional β cells from stem cells. Embryonal carcinoma (EC) stem cells are pluripotent cells which can differentiate into all cell types. The present study was carried out to establish a simple nonselective inductive culture system for generation of IPCs from P19 EC cells by 1-2 weeks old mouse Pancreas Extract (MPE). Since, mouse pancreatic islets undergo further remodeling and maturation for 2-3 weeks after birth, we hypothesized that the mouse neonatal MPE contains essential factors to induce in vitro differentiation of pancreatic lineages. Pluripotency of P19 cells were first confirmed by expression analysis of stem cell markers, Oct3/4, Sox-2 and Nanog. In order to induce differentiation, the cells were cultured in a medium supplemented by different concentrations of MPE (50, 100, 200 and 300 µg/ml). The results showed that P19 cells could differentiate into IPCs and form dithizone-positive cell clusters. The generated P19-derived IPCs were immunoreactive to proinsulin, insulin and insulin receptor beta. The expression of pancreatic β cell genes including, PDX-1, INS1 and INS2 were also confirmed. The peak response at the 100 µg/ml MPE used for investigation of EP300 and CREB1 gene expression. When stimulated with glucose, these cells synthesized and secreted insulin. Network analysis of the key transcription factors (PDX-1, EP300, CREB1) during the generation of IPCs resulted in introduction of novel regulatory candidates such as MIR17, and VEZF1 transcription factors, as well as MORN1, DKFZp761P0212, and WAC proteins. Altogether, we demonstrated the possibility of generating IPCs from undifferentiated EC cells, with the characteristics of pancreatic β cells. The derivation of pancreatic cells from EC cells which are ES cell siblings would provide a valuable experimental tool in study of pancreatic development and function as well as rapid production of IPCs for transplantation.

Fariba Esmaeili - One of the best experts on this subject based on the ideXlab platform.

  • Induction of pancreatic β cell gene expression in mesenchymal stem cells.
    Cell biology international, 2016
    Co-Authors: Zahra Mehrfarjam, Fariba Esmaeili, Leila Shabani, Esmaeil Ebrahimie
    Abstract:

    Transdifferentiattion potential of mesenchymal stem cells (MSCs) into insulin-producing cells (IPCs) has been suggested recently. In our recent works, we demonstrated the high performance of mouse neonate Pancreas Extract (MPE) in the production of functional IPCs from carcinoma stem cells. In this study, MPE was used to generate IPCs from MSCs without any genetic manipulation. To this end, bone marrow MSCs were isolated and characterized. In order to differentiate, MSCs were induced by selection of nestin-expressing cells and treatment with 100 μg/mL MPE. Morphological features of the differenti-ated cells were confirmed by dithizone staining. Immunoreactivity to insulin receptor beta, proinsulin, insulin, and C-peptide was observed by immunoflourescence. We also quantified glucose-dependent insulin production and secretion by ELISA. Real-time PCR indicated the expressions of β cell-related genes, PDX-1, INS1, INS2, EP300, and CREB1, in IPC cells. Possible pathways governed by CREB1, EP300, and PDX-1 transcription factors in differentiation of MSCs to IPCs were determined based on Gene Set Enrichment (GSE) approach at P = 0.05. Pathway discovery highlighted the negative regulatory effects of MIR124-2, HDAC5 protein, REST, and NR0B2 transcription factors on expression of CREB1, EP300, and PDX-1 and inhabitation of IPC differentiations. In contrast, a crosstalk between FOXA2 and TCF7L2 transcription factors, DNA-PK complex, KAT2B protein positively interacting with PDX-1, CREB1, EP300 resulted in the induction of IPC and following insulin production. In conclusion, we report an efficient, simple, and easy method for production of functional IPCs from MSCs by MPE treatment.

  • Induction of pancreatic b cell gene expression in mesenchymal stem cells
    2016
    Co-Authors: Zahra Mehrfarjam, Fariba Esmaeili, Leila Shabani, Esmaeil Ebrahimie
    Abstract:

    Transdifferentiattion potential of mesenchymal stem cells (MSCs) into insulin-producing cells (IPCs) has been suggestedrecently. In our recent works, we demonstrated the high performance of mouse neonate Pancreas Extract (MPE) in theproduction of functional IPCs fromcarcinoma stemcells. In this study, MPE was used to generate IPCs from MSCs without anygenetic manipulation. To this end, bone marrow MSCs were isolated and characterized. In order to differentiate, MSCs wereinduced by selection of nestin-expressing cells and treatment with 100mg/mLMPE. Morphological features of the differentiatedcells were confirmed by dithizone staining. Immunoreactivity to insulin receptor beta, proinsulin, insulin, and C-peptide wasobserved by immunoflourescence. We also quantified glucose-dependent insulin production and secretion by ELISA. Real-timePCR indicated the expressions of b cell-related genes, PDX-1, INS1, INS2, EP300, and CREB1, in IPC cells. Possible pathwaysgoverned by CREB1, EP300, and PDX-1 transcription factors in differentiation ofMSCs to IPCswere determined based on GeneSet Enrichment (GSE) approach at P¼0.05. Pathway discovery highlighted the negative regulatory effects of MIR124-2,HDAC5protein, REST, and NR0B2 transcription factors on expression of CREB1, EP300, and PDX-1 and inhabitation of IPCdifferentiations. In contrast, a crosstalk between FOXA2 and TCF7L2 transcription factors, DNA-PK complex, KAT2B proteinpositively interacting with PDX-1, CREB1, EP300 resulted in the induction of IPC and following insulin production. Inconclusion, we report an efficient, simple, and easy method for production of functional IPCs from MSCs by MPE treatment.Keywords: insulin-producing cells; mesenchymal stem cells; nestin-positive cells; Pancreas Extract; stem cell differentiation

  • Efficient and simple production of insulin-producing cells from embryonal carcinoma stem cells using mouse neonate Pancreas Extract, as a natural inducer.
    PloS one, 2014
    Co-Authors: Marzieh Ebrahimie, Fariba Esmaeili, Fariba Houshmand, Somayeh Cheraghi, Leila Shabani, Esmaeil Ebrahimie
    Abstract:

    An attractive approach to replace the destroyed insulin-producing cells (IPCs) is the generation of functional β cells from stem cells. Embryonal carcinoma (EC) stem cells are pluripotent cells which can differentiate into all cell types. The present study was carried out to establish a simple nonselective inductive culture system for generation of IPCs from P19 EC cells by 1-2 weeks old mouse Pancreas Extract (MPE). Since, mouse pancreatic islets undergo further remodeling and maturation for 2-3 weeks after birth, we hypothesized that the mouse neonatal MPE contains essential factors to induce in vitro differentiation of pancreatic lineages. Pluripotency of P19 cells were first confirmed by expression analysis of stem cell markers, Oct3/4, Sox-2 and Nanog. In order to induce differentiation, the cells were cultured in a medium supplemented by different concentrations of MPE (50, 100, 200 and 300 µg/ml). The results showed that P19 cells could differentiate into IPCs and form dithizone-positive cell clusters. The generated P19-derived IPCs were immunoreactive to proinsulin, insulin and insulin receptor beta. The expression of pancreatic β cell genes including, PDX-1, INS1 and INS2 were also confirmed. The peak response at the 100 µg/ml MPE used for investigation of EP300 and CREB1 gene expression. When stimulated with glucose, these cells synthesized and secreted insulin. Network analysis of the key transcription factors (PDX-1, EP300, CREB1) during the generation of IPCs resulted in introduction of novel regulatory candidates such as MIR17, and VEZF1 transcription factors, as well as MORN1, DKFZp761P0212, and WAC proteins. Altogether, we demonstrated the possibility of generating IPCs from undifferentiated EC cells, with the characteristics of pancreatic β cells. The derivation of pancreatic cells from EC cells which are ES cell siblings would provide a valuable experimental tool in study of pancreatic development and function as well as rapid production of IPCs for transplantation.

  • Differentiation of Embryonal Carcinoma Stem Cells into Insulin-Producing Cells by Using Pancreas Extract in Vitro
    Iranian Journal of Endocrinology and Metabolism, 2013
    Co-Authors: Marzyeh Ebrahimihafshajani, Fariba Esmaeili, Fariba Houshmand
    Abstract:

    Introduction: Type I diabetes mellitus results from the autoimmune destruction of the β cells in pancreatic islets. Currently, extensive research is being conducted on the generation of insulin-producing cells (IPCs) from stem cells. P19 embryonal carcinoma cells are multipotent and can differentiate into cell types of all three germ layers. In this study, the differentiation of P19 cells into IPCs by using mouse Pancreas Extract (MPE) was investigated. Materials and Methods: Embryoid bodies (EBs) obtained from P19 cells were cultured in medium containing 3 fetal bovine serum, supplemented by concentration of 50, 100, 200,300 μg/mL MPE for 7-14 days. Dithizone (DTZ) staining was used to detect IPCs derived from EBs in vitro. Mouse monoclonal insulin-proinsulin and monoclonal insulin receptor beta antibodies were used for immunoflourescence. Insulin content from the cells and insulin secreted by differentiated cells in response to concentrations of 5.5 and 25 mM glucose were measured using ELISA kits. Results: DTZ-positive cells showed purple-red clusters. immunoflourescence indicated expression of Beta cell markers (insulin-proinsulin and insulin receptor beta) in these cells. Increasing glucose concentration, caused more insulin to be secreted by differentiated cells. Conclusions: P19 cells can in the presence of Pancreas Extract differentiate to cell producing and secreting insulin cells. Differentiated cells can increase insulin secretion in response to increasing glucose medium.

N. M. Loskutoff - One of the best experts on this subject based on the ideXlab platform.

  • Comparison of a recombinant trypsin with the porcine pancreatic Extract on sperm used for the in vitro production of bovine embryos.
    Theriogenology, 2008
    Co-Authors: K. J. Mattson, B. R. Devlin, N. M. Loskutoff
    Abstract:

    The objective was to compare the effects of treating bovine semen with two trypsin products (the porcine Pancreas Extract and a recombinant) and a control (no trypsin) on in vitro embryo production. Our hypothesis was that the trypsin treatments would not cause any significant difference in fertilization and embryo development as compared to the control. Semen was washed through a gradient system containing a porcine-origin trypsin, a recombinant bovine-sequence trypsin, or the control (no trypsin). Oocytes (n=3036) were collected from abbatoir-derived ovaries, matured for 24h, and allocated into three groups: porcine trypsin (n=1040), recombinant trypsin (n=972), and control (n=1024). Ova were inseminated with 1 x 10(6) motile sperm/mL and cultured for 18-24h. Thereafter, presumptive zygotes were cultured for 7 days in 50 microL G1/G2 micro-droplets under mineral oil. Overall, sperm motility was lower before than after each treatment (mean of 51.4% versus 70.2%, respectively; P

  • 7 EFFECTS OF DIFFERENT TRYPSIN SOURCES AND CONCENTRATIONS ON THE VIABILITY OF BOVINE SPERM PRE- AND POST-CRYOPRESERVATION
    Reproduction Fertility and Development, 2007
    Co-Authors: B. A. Blevins, S. Steenson, N. M. Loskutoff
    Abstract:

    The goal of this research was to investigate the effect of different sources and concentrations of trypsin on the viability of bovine sperm as a potential method for removing pathogens similar to the washing methods developed for embryos. Trypsin derived from porcine Pancreas (Sigma-Aldrich, St Louis, MO, USA) at 2.5% and 0.25% was compared to the recombinant human sequence (TrypLE Select; Invitrogen, Carlsbad, CA, USA) at 10× and 1× concentrations. Cryopreserved bovine sperm (n = 3 bulls) were thawed and processed using discontinuous (90/45) Percoll density gradient centrifugation; the sperm pellets were then washed (10 min at 300g) in TL-HEPES Solution (Cambrex Corp., East Rutherford, NJ, USA) and then resuspended in 1 mL of the same medium. Aliquots of 200 µL of the washed sperm were then added to 1 mL of each of the 4 trypsin treatments as well as a negative control (without trypsin) and incubated at room temperature. Aliquots (25 µL) of each treatment were examined for progressive motility after 5 min. As a result, the control sperm (no trypsin) increased progressive motility by 6.7% and the 1× TrypLE treatment by 9.3%. However, the 10× TrypLE Select and the 10× and 1× porcine Pancreas Extracts decreased progressive motility by 8.3, 29.0, and 4.0%, respectively. The objective of the second experiment was to determine if the treatment of bovine semen with trypsin (1× TrypLE Select and 0.25% porcine Pancreas Extract) before or after cryopreservation would affect sperm quality as compared to cryopreservation without trypsin treatment. Raw semen (n = 6 bulls) was collected, evaluated, cryopreserved, and then thawed using a standard bovine method (Biladyl®; Minitube, Verona, WI, USA) without further treatment (control) or after treatment with one of two trypsin treatments (density gradient centrifugation with 1× TrypLE Select or 0.25% porcine Pancreas Extract in the 45% Percoll layer and a soybean trypsin in activator (Sigma) in the 90% layer) either before freezing (Treat–Freeze) or after thawing (Freeze–Treat). The results for the 6 individual bull samples were comparable and are presented as means (± SEM) compared to the cryopreserved control (no trypsin treatment). Using the Mann–Whitney Rank Sum Test, no differences (P > 0.05) were found in any of the parameters comparing the crypreserved controls (no trypsin treatment) and the 4 treatments: Freeze–Treat vs. Treat–Freeze using either the recombinant TrypLE Select (1×) or the porcine Pancreas Extract (0.25%). These results suggest that trypsin treatment, before or after cryopreservation, can be used safely on bovine sperm without affecting viability in vitro. Table 1.Comparison of cryopreserved bovine semen without and with various treatments

Song Cheol Kim - One of the best experts on this subject based on the ideXlab platform.

  • In vitro differentiation of human adipose tissue-derived stem cells into cells with pancreatic phenotype by regenerating Pancreas Extract
    Biochemical and biophysical research communications, 2008
    Co-Authors: Jiyeon Lee, Duck Jong Han, Song Cheol Kim
    Abstract:

    Pancreas Extract from regenerating Pancreas after partial pancreatectomy is known to contain factors that induce islet neogenesis in animals with streptozotocin (STZ)-induced diabetes [A.A. Hardikar, R.R. Bhonde, Modulating experimental diabetes by treatment with cytosolic Extract from the regenerating Pancreas, Diabetes Res. Clin. Pract. 46 (1999) 203-211]. In this study, we evaluate the effects of regenerating Pancreas Extract (RPE) from 90% partially pancreatectomized rats on induction of pancreatic differentiation of human adipose tissue-derived stem cells (hASCs). We found that undifferentiated hASCs expressed OCT-3/4, Nanog, and REX-1, markers of embryonic stem cells (ESCs). Genes involved in early Pancreas development showed increased expression in RPE-treated culture. Sox17 and IPF-1 were expressed only in RPE-treated culture. Immunocytochemical analysis showed C-peptide-positive cells in RPE-treated culture but not in undifferentiated hASCs. In conclusion, hASCs have the characteristics of ESCs and the potential to differentiate into Pancreas cell lineages phenotypically in response to RPE.

Leila Shabani - One of the best experts on this subject based on the ideXlab platform.

  • Induction of pancreatic β cell gene expression in mesenchymal stem cells.
    Cell biology international, 2016
    Co-Authors: Zahra Mehrfarjam, Fariba Esmaeili, Leila Shabani, Esmaeil Ebrahimie
    Abstract:

    Transdifferentiattion potential of mesenchymal stem cells (MSCs) into insulin-producing cells (IPCs) has been suggested recently. In our recent works, we demonstrated the high performance of mouse neonate Pancreas Extract (MPE) in the production of functional IPCs from carcinoma stem cells. In this study, MPE was used to generate IPCs from MSCs without any genetic manipulation. To this end, bone marrow MSCs were isolated and characterized. In order to differentiate, MSCs were induced by selection of nestin-expressing cells and treatment with 100 μg/mL MPE. Morphological features of the differenti-ated cells were confirmed by dithizone staining. Immunoreactivity to insulin receptor beta, proinsulin, insulin, and C-peptide was observed by immunoflourescence. We also quantified glucose-dependent insulin production and secretion by ELISA. Real-time PCR indicated the expressions of β cell-related genes, PDX-1, INS1, INS2, EP300, and CREB1, in IPC cells. Possible pathways governed by CREB1, EP300, and PDX-1 transcription factors in differentiation of MSCs to IPCs were determined based on Gene Set Enrichment (GSE) approach at P = 0.05. Pathway discovery highlighted the negative regulatory effects of MIR124-2, HDAC5 protein, REST, and NR0B2 transcription factors on expression of CREB1, EP300, and PDX-1 and inhabitation of IPC differentiations. In contrast, a crosstalk between FOXA2 and TCF7L2 transcription factors, DNA-PK complex, KAT2B protein positively interacting with PDX-1, CREB1, EP300 resulted in the induction of IPC and following insulin production. In conclusion, we report an efficient, simple, and easy method for production of functional IPCs from MSCs by MPE treatment.

  • Induction of pancreatic b cell gene expression in mesenchymal stem cells
    2016
    Co-Authors: Zahra Mehrfarjam, Fariba Esmaeili, Leila Shabani, Esmaeil Ebrahimie
    Abstract:

    Transdifferentiattion potential of mesenchymal stem cells (MSCs) into insulin-producing cells (IPCs) has been suggestedrecently. In our recent works, we demonstrated the high performance of mouse neonate Pancreas Extract (MPE) in theproduction of functional IPCs fromcarcinoma stemcells. In this study, MPE was used to generate IPCs from MSCs without anygenetic manipulation. To this end, bone marrow MSCs were isolated and characterized. In order to differentiate, MSCs wereinduced by selection of nestin-expressing cells and treatment with 100mg/mLMPE. Morphological features of the differentiatedcells were confirmed by dithizone staining. Immunoreactivity to insulin receptor beta, proinsulin, insulin, and C-peptide wasobserved by immunoflourescence. We also quantified glucose-dependent insulin production and secretion by ELISA. Real-timePCR indicated the expressions of b cell-related genes, PDX-1, INS1, INS2, EP300, and CREB1, in IPC cells. Possible pathwaysgoverned by CREB1, EP300, and PDX-1 transcription factors in differentiation ofMSCs to IPCswere determined based on GeneSet Enrichment (GSE) approach at P¼0.05. Pathway discovery highlighted the negative regulatory effects of MIR124-2,HDAC5protein, REST, and NR0B2 transcription factors on expression of CREB1, EP300, and PDX-1 and inhabitation of IPCdifferentiations. In contrast, a crosstalk between FOXA2 and TCF7L2 transcription factors, DNA-PK complex, KAT2B proteinpositively interacting with PDX-1, CREB1, EP300 resulted in the induction of IPC and following insulin production. Inconclusion, we report an efficient, simple, and easy method for production of functional IPCs from MSCs by MPE treatment.Keywords: insulin-producing cells; mesenchymal stem cells; nestin-positive cells; Pancreas Extract; stem cell differentiation

  • Efficient and simple production of insulin-producing cells from embryonal carcinoma stem cells using mouse neonate Pancreas Extract, as a natural inducer.
    PloS one, 2014
    Co-Authors: Marzieh Ebrahimie, Fariba Esmaeili, Fariba Houshmand, Somayeh Cheraghi, Leila Shabani, Esmaeil Ebrahimie
    Abstract:

    An attractive approach to replace the destroyed insulin-producing cells (IPCs) is the generation of functional β cells from stem cells. Embryonal carcinoma (EC) stem cells are pluripotent cells which can differentiate into all cell types. The present study was carried out to establish a simple nonselective inductive culture system for generation of IPCs from P19 EC cells by 1-2 weeks old mouse Pancreas Extract (MPE). Since, mouse pancreatic islets undergo further remodeling and maturation for 2-3 weeks after birth, we hypothesized that the mouse neonatal MPE contains essential factors to induce in vitro differentiation of pancreatic lineages. Pluripotency of P19 cells were first confirmed by expression analysis of stem cell markers, Oct3/4, Sox-2 and Nanog. In order to induce differentiation, the cells were cultured in a medium supplemented by different concentrations of MPE (50, 100, 200 and 300 µg/ml). The results showed that P19 cells could differentiate into IPCs and form dithizone-positive cell clusters. The generated P19-derived IPCs were immunoreactive to proinsulin, insulin and insulin receptor beta. The expression of pancreatic β cell genes including, PDX-1, INS1 and INS2 were also confirmed. The peak response at the 100 µg/ml MPE used for investigation of EP300 and CREB1 gene expression. When stimulated with glucose, these cells synthesized and secreted insulin. Network analysis of the key transcription factors (PDX-1, EP300, CREB1) during the generation of IPCs resulted in introduction of novel regulatory candidates such as MIR17, and VEZF1 transcription factors, as well as MORN1, DKFZp761P0212, and WAC proteins. Altogether, we demonstrated the possibility of generating IPCs from undifferentiated EC cells, with the characteristics of pancreatic β cells. The derivation of pancreatic cells from EC cells which are ES cell siblings would provide a valuable experimental tool in study of pancreatic development and function as well as rapid production of IPCs for transplantation.