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| Status |
Public on Nov 10, 2011 |
| Title |
Synergism between Activin A and BMP4 in directing the formation of definitive endoderm in human embryonic stem cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Human embryonic stem cells (HESCs) herald tremendous promise for the production of clinically useful cell types for the treatment of injury and disease. Numerous reports demonstrate their differentiation into definitive endoderm (DE) cells, the germ layer from which pancreatic β cells and hepatocytes arise, solely from exposure to a high dose of recombinant Activin/Nodal. Here, we show that combining a second related ligand, BMP4, in combination with Activin A yields 15 to 20% more DE as compared to Activin A alone. The addition of recombinant BMP4 accelerates the downregulation of pluripotency factors, particularly SOX2, and results in upregulation of endogenous BMP2 and BMP4, which in turn leads to elevated levels of phospho-SMAD1/5/8 over the next three days of differentiation. Combined Activin A and BMP4 treatment also leads to an increase in the expression of DE genes CXCR4, SOX17 and FOXA2 when compared to Activin A addition alone. Comparative microarray studies between DE cells harvested on day 3 of differentiation further reveal a novel set of genes upregulated in response to initial BMP4 exposure. Several of these, including APLNR, LRIG3, MCC and LZTS1, are expressed either in the mouse primitive streak, the site of DE formation, or in nascent DE itself. Thus, this synergism between Activin A and BMP4 during the in vitro differentiation of HESC into DE suggests a complex interplay between BMP and Activin/Nodal signaling during the in vivo allocation and expansion of the endoderm lineage.
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| Overall design |
3 biological replicates of 3-day ActivinA treated HES3 human stem cell culture were compared to 3-day ActivinA+Bmp4 treated HES3 human stem cell culture and observed for differential genes expression
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| Contributor(s) |
Wong KY, Teo AK, Ali Y, Stanton LW, Dunn NR |
| Citation(s) |
22893457 |
| Submission date |
Jul 13, 2011 |
| Last update date |
Mar 20, 2017 |
| Contact name |
Kee Yew Wong |
| Organization name |
Genome Institute of Singapore
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| Department |
Stem cell Biology
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| Lab |
Stem cell Genomics
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| Street address |
60, Biopolis Street, #02-01
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| City |
Singapore |
| ZIP/Postal code |
138672 |
| Country |
Singapore |
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| Platforms (1) |
| GPL6883 |
Illumina HumanRef-8 v3.0 expression beadchip |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA144583 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE30630_RAW.tar |
3.9 Mb |
(http)(custom) |
TAR |
| GSE30630_non-normalized.txt.gz |
635.4 Kb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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