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Development ePress online publication date 3 Dec 2003
doi: 10.1242/dev.00921
Research article
Global expression analysis of gene regulatory pathways during endocrine pancreatic development
Guoqiang Gu,
James M. Wells,
David Dombkowski,
Fred Preffer,
Bruce Aronow,
and
Douglas A. Melton*
* Author for correspondence (e-mail: dmelton{at}biohp.harvard.edu)
To define genetic pathways that regulate development of the endocrine pancreas, we generated transcriptional profiles of enriched cells isolated from four biologically significant stages of endocrine pancreas development: endoderm before pancreas specification, early pancreatic progenitor cells, endocrine progenitor cells and adult islets of Langerhans. These analyses implicate new signaling pathways in endocrine pancreas development, and identified sets of known and novel genes that are temporally regulated, as well as genes that spatially define developing endocrine cells from their neighbors. The differential expression of several genes from each time point was verified by RT-PCR and in situ hybridization. Moreover, we present preliminary functional evidence suggesting that one transcription factor encoding gene (Myt1), which was identified in our screen, is expressed in endocrine progenitors and may regulate 
, 
and 
cell development. In addition to identifying new genes that regulate endocrine cell fate, this global gene expression analysis has uncovered informative biological trends that occur during endocrine differentiation.
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22(10):
2353 - 2363.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
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October 1, 2008;
57(10):
2755 - 2761.
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[PDF]
|
|
|
|
|
|
|
I. Artner, Y. Hang, M. Guo, G. Gu, and R. Stein
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198(2):
271 - 279.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Oliver-Krasinski and D. A. Stoffers
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Genes & Dev.,
August 1, 2008;
22(15):
1998 - 2021.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Yoshida, N. Shiraki, H. Baba, M. Goto, S. Fujiwara, K. Kume, and S. Kume
Expression patterns of epiplakin1 in pancreas, pancreatic cancer and regenerating pancreas.
Genes Cells,
July 1, 2008;
13(7):
667 - 678.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Shiraki, K. Umeda, N. Sakashita, M. Takeya, K. Kume, and S. Kume
Differentiation of mouse and human embryonic stem cells into hepatic lineages.
Genes Cells,
July 1, 2008;
13(7):
731 - 746.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Shiraki, T. Yoshida, K. Araki, A. Umezawa, Y. Higuchi, H. Goto, K. Kume, and S. Kume
Guided Differentiation of Embryonic Stem Cells into Pdx1-Expressing Regional-Specific Definitive Endoderm
Stem Cells,
April 1, 2008;
26(4):
874 - 885.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Suri, J. J. Walters, H. W. Rohrs, M. L. Gross, and E. R. Unanue
First Signature of Islet {beta}-Cell-Derived Naturally Processed Peptides Selected by Diabetogenic Class II MHC Molecules
J. Immunol.,
March 15, 2008;
180(6):
3849 - 3856.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. White, C. Lee May, R. N. Lamounier, J. E. Brestelli, and K. H. Kaestner
Defining Pancreatic Endocrine Precursors and Their Descendants
Diabetes,
March 1, 2008;
57(3):
654 - 668.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Serafimidis, I. Rakatzi, V. Episkopou, M. Gouti, and A. Gavalas
Novel Effectors of Directed and Ngn3-Mediated Differentiation of Mouse Embryonic Stem Cells into Endocrine Pancreas Progenitors
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January 1, 2008;
26(1):
3 - 16.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Xu, G. Xu, B. Liu, and G. Gu
Cre reconstitution allows for DNA recombination selectively in dual-marker-expressing cells in transgenic mice
Nucleic Acids Res.,
October 8, 2007;
35(19):
e126 - e126.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. B. Nelson, A. E. Schaffer, and M. Sander
The transcription factors Nkx6.1 and Nkx6.2 possess equivalent activities in promoting beta-cell fate specification in Pdx1+ pancreatic progenitor cells
Development,
July 1, 2007;
134(13):
2491 - 2500.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. T. Ku, J. Chai, Y.-J. Kim, P. White, S. Purohit-Ghelani, K. H. Kaestner, and J. S. Bromberg
Insulin-Expressing Colonies Developed From Murine Embryonic Stem Cell-Derived Progenitors
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April 1, 2007;
56(4):
921 - 929.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Sugiyama, R. T. Rodriguez, G. W. McLean, and S. K. Kim
Conserved markers of fetal pancreatic epithelium permit prospective isolation of islet progenitor cells by FACS
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January 2, 2007;
104(1):
175 - 180.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. B. McLean, K. A. D'Amour, K. L. Jones, M. Krishnamoorthy, M. J. Kulik, D. M. Reynolds, A. M. Sheppard, H. Liu, Y. Xu, E. E. Baetge, et al.
Activin A Efficiently Specifies Definitive Endoderm from Human Embryonic Stem Cells Only When Phosphatidylinositol 3-Kinase Signaling Is Suppressed
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January 1, 2007;
25(1):
29 - 38.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. R. Treff, R. K. Vincent, M. L. Budde, V. L. Browning, J. F. Magliocca, V. Kapur, and J. S. Odorico
Differentiation of Embryonic Stem Cells Conditionally Expressing Neurogenin 3
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November 1, 2006;
24(11):
2529 - 2537.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Petri, J. Ahnfelt-Ronne, K. S. Frederiksen, D. G. Edwards, D. Madsen, P. Serup, J. Fleckner, and R S. Heller
The effect of neurogenin3 deficiency on pancreatic gene expression in embryonic mice.
J. Mol. Endocrinol.,
October 1, 2006;
37(2):
301 - 316.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Hua, Y.-Q. Zhang, S. Dabernat, M. Kritzik, D. Dietz, L. Sterling, and N. Sarvetnick
BMP4 Regulates Pancreatic Progenitor Cell Expansion through Id2
J. Biol. Chem.,
May 12, 2006;
281(19):
13574 - 13580.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. R. Lawlor, L. Soucek, L. Brown-Swigart, K. Shchors, C. U. Bialucha, and G. I. Evan
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4591 - 4601.
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[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Sinner, P. Kirilenko, S. Rankin, E. Wei, L. Howard, M. Kofron, J. Heasman, H. R. Woodland, and A. M. Zorn
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133(10):
1955 - 1966.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Hara, R. F. Dizon, B. S. Glick, C. S. Lee, K. H. Kaestner, D. W. Piston, and V. P. Bindokas
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May 1, 2006;
290(5):
E1041 - E1047.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. P. Raikwar, T. Mueller, and N. Zavazava
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Physiology,
February 1, 2006;
21(1):
19 - 28.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Artner, J. Le Lay, Y. Hang, L. Elghazi, J. C. Schisler, E. Henderson, B. Sosa-Pineda, and R. Stein
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February 1, 2006;
55(2):
297 - 304.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. D. Henseleit, S. B. Nelson, K. Kuhlbrodt, J. C. Hennings, J. Ericson, and M. Sander
NKX6 transcription factor activity is required for {alpha}- and {beta}-cell development in the pancreas
Development,
July 1, 2005;
132(13):
3139 - 3149.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Shiraki, C.-J. Lai, Y. Hishikari, and S. Kume
TGF-{beta} signaling potentiates differentiation of embryonic stem cells to Pdx-1 expressing endodermal cells
Genes Cells,
June 1, 2005;
10(6):
503 - 516.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Mutsuga, T. Shahar, J. G. Verbalis, C. C. Xiang, M. J. Brownstein, and H. Gainer
Regulation of Gene Expression in Magnocellular Neurons in Rat Supraoptic Nucleus during Sustained Hypoosmolality
Endocrinology,
March 1, 2005;
146(3):
1254 - 1267.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Wang, S. Ramanadham, Z. A. Ma, S. Bao, D. J. Mancuso, R. W. Gross, and J. Turk
Group VIA Phospholipase A2 Forms a Signaling Complex with the Calcium/Calmodulin-dependent Protein Kinase II{beta} Expressed in Pancreatic Islet {beta}-Cells
J. Biol. Chem.,
February 25, 2005;
280(8):
6840 - 6849.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Giacopelli, R. Marciano, A. Pistorio, P. Catarsi, S. Canini, G. Karsenty, and R. Ravazzolo
Polymorphisms in the osteopontin promoter affect its transcriptional activity
Physiol Genomics,
December 15, 2004;
20(1):
87 - 96.
[Abstract]
[Full Text]
[PDF]
|
|
|
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