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| Status |
Public on Jun 01, 2013 |
| Title |
Notch-HES1 signaling axis controls hemato-endothelial fate decisions of human embyronic and induced pluripotent cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Notch signaling regulates several cellular processes including cell fate decisions and proliferation in both invertebrates and mice. However, comparatively less is known about the role of Notch during early human development. Here, we examined the function of Notch signaling during hematopoietic lineage specification from human pluripotent stem cells (hPSCs) of both embryonic and adult fibroblast origin. Using immobilized Notch ligands and siRNA to Notch receptors we have demonstrated that Notch1, but not Notch2 activation, induced HES1 expression and generation of committed hematopoietic progenitors. Using gain and loss of function approaches, this was shown to be attributed to Notch signaling regulation through HES1, that dictated cell fate decisions from bipotent precursors either to the endothelial or hematopoietic lineages at the clonal level. Our study reveals a previously unappreciated role for the Notch pathway during early human hematopoiesis, whereby Notch signaling via HES1 represents a toggle switch of hematopoietic vs. endothelial fate specification.
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| Overall design |
Human pluripotent stem cells (hPSCs) have differentiation potential into three embryonic germ layers including blood. Notch signaling is one of important signaling pathways involved in blood differentiation of hPSCs. Thus, in order to examine the effect of Notch signaling pathways during hematopoietic differentiation of hPSCs, embryoid bodies (EBs) were formed and cultured for 10 days in the combination of cytokines and growth factors (Chadwick, Blood, 2003; 300 ng/ml of SCF, 300 ng/ml of Flt-3L, 10 ng/ml of IL-3, 10 ng/ml of IL-6, and 50 ng/ml of G-CSF) to induce differentiation into blood. Additionally, CD31+CD45- bipotent hemogenic precursors were isolated from day10 hematopoietic EBs (Wang et al., Immunity, 2004)
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| Contributor(s) |
Lee J, Werbowetski-Ogilvie TE, Lee J, McIntyre BA, Schnerch A, Hong S, Park I, Daley GQ, Bernstein ID, Bhatia M |
| Citation(s) |
23733337 |
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| Submission date |
May 29, 2013 |
| Last update date |
Aug 10, 2018 |
| Contact name |
Mickie Bhatia |
| E-mail(s) |
mbhatia@mcmaster.ca
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| Organization name |
McMaster University
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| Department |
Stem Cell and Cancer Research Institute (SCC-RI)
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| Street address |
1200 Main Street West
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| City |
Hamilton |
| State/province |
Ontario |
| ZIP/Postal code |
L8N 3Z5 |
| Country |
Canada |
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| Platforms (1) |
| GPL96 |
[HG-U133A] Affymetrix Human Genome U133A Array |
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| Samples (8)
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| GSM1150648 |
Undifferentiated H9 cells, biological rep 1 |
| GSM1150649 |
Undifferentiated H9 cells, biological rep 2 |
| GSM1150650 |
Day 10 hematopoietic EB cells, bilogical rep 1 |
| GSM1150651 |
Day 10 hematopoietic EB cells, bilogical rep 2 |
| GSM1150652 |
Day 10 hematopoietic EB cells, bilogical rep 3 |
| GSM1150653 |
CD31pos-CD45neg-PFV, biological rep 1 |
| GSM1150654 |
CD31pos-CD45neg-PFV, biological rep 2 |
| GSM1150655 |
CD31pos-CD45neg-PFV, biological rep 3 |
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| Relations |
| BioProject |
PRJNA205824 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE47466_RAW.tar |
26.8 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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