Differentiation of embryonic stem cells conditionally expressing neurogenin 3

Nathan R. Treff, Robert K. Vincent, Melisa L. Budde, Victoria L. Browning, Joseph F. Magliocca, Vivek Kapur, Jon S. Odorico

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Expression of the proendocrine gene neurogenin 3 (Ngn3) is required for the development of pancreatic islets. To better characterize the molecular events regulated by Ngn3 during development, we have determined the expression profiles of murine embryonic stem cells (mESCs) uniformly induced to overexpress Ngn3. An mESC line was created in order to induce Ngn3 by adding doxycycline to the culture medium. Genome-wide microarray analysis was performed to identify genes regulated by Ngn3 in a variety of contexts, including undifferentiated ESCs and differentiating embryoid bodies (EBs). Genes regulated by Ngn3 in a context-independent manner were identified and analyzed using systematic gene ontology tools. This analysis revealed Notch signaling as the most significantly regulated signaling pathway (p = .009). This result is consistent with the hypothesis that Ngn3 expression makes the cell competent for Notch signaling to be activated and, conversely, more sensitive to Notch signaling inhibition. Indeed, EBs induced to express Ngn3 were significantly more sensitive to γ-secretase inhibitor-mediated Notch signaling inhibition (p < .0001) when compared with uninduced EBs. Moreover, we find that Ngn3 induction in differentiating ESCs results in significant increases in insulin, glucagon, and somatostatin expression.

Original languageEnglish (US)
Pages (from-to)2529-2537
Number of pages9
JournalSTEM CELLS
Volume24
Issue number11
DOIs
StatePublished - Nov 8 2006

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Embryoid Bodies
Embryonic Stem Cells
Amyloid Precursor Protein Secretases
Gene Ontology
Doxycycline
Microarray Analysis
Somatostatin
Glucagon
Islets of Langerhans
Genes
Culture Media
Genome
Insulin
Gene Expression
Cell Line

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Cite this

Treff, N. R., Vincent, R. K., Budde, M. L., Browning, V. L., Magliocca, J. F., Kapur, V., & Odorico, J. S. (2006). Differentiation of embryonic stem cells conditionally expressing neurogenin 3. STEM CELLS, 24(11), 2529-2537. https://doi.org/10.1634/stemcells.2006-0082
Treff, Nathan R. ; Vincent, Robert K. ; Budde, Melisa L. ; Browning, Victoria L. ; Magliocca, Joseph F. ; Kapur, Vivek ; Odorico, Jon S. / Differentiation of embryonic stem cells conditionally expressing neurogenin 3. In: STEM CELLS. 2006 ; Vol. 24, No. 11. pp. 2529-2537.
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Treff, NR, Vincent, RK, Budde, ML, Browning, VL, Magliocca, JF, Kapur, V & Odorico, JS 2006, 'Differentiation of embryonic stem cells conditionally expressing neurogenin 3', STEM CELLS, vol. 24, no. 11, pp. 2529-2537. https://doi.org/10.1634/stemcells.2006-0082

Differentiation of embryonic stem cells conditionally expressing neurogenin 3. / Treff, Nathan R.; Vincent, Robert K.; Budde, Melisa L.; Browning, Victoria L.; Magliocca, Joseph F.; Kapur, Vivek; Odorico, Jon S.

In: STEM CELLS, Vol. 24, No. 11, 08.11.2006, p. 2529-2537.

Research output: Contribution to journalArticle

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AU - Odorico, Jon S.

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Treff NR, Vincent RK, Budde ML, Browning VL, Magliocca JF, Kapur V et al. Differentiation of embryonic stem cells conditionally expressing neurogenin 3. STEM CELLS. 2006 Nov 8;24(11):2529-2537. https://doi.org/10.1634/stemcells.2006-0082