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| Status |
Public on Dec 31, 2015 |
| Title |
Vascular niche induction of hematopoietic progenitors from pluripotent stem cells |
| Organisms |
Macaca nemestrina; Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Pluripotent stem cells (PSC) represent an alternative source of hematopoietic stem cells (HSCs). Clinical translation is impeded by limited engraftment of human (h)PSC-multipotent progenitor cells (MPP). This barrier suggests that additional cues are required for definitive hematopoiesis. We hypothesized that vascular niche producing Notch ligands Jagged-1 (JAG1) and Delta-like ligand-4 (DLL4) would drive definitive hematopoiesis. To test our hypothesis, hes2 human embryonic stem cells (hESC) 2 and Macaca nemestrina (Mn) iPSC line-7 were differentiated with cytokines ± endothelial cells (EC), which express JAG1 and DLL4. EC co-culture supported emergence of 8-fold more CD34+CD45+ cells compared to co-culture with cytokines ± ECs with JAG1 or DLL4 knockdown. EC-induced cells exhibit Notch activation and express HSC-specific targets of Notch signaling RUNX1 and GATA2. EC-induced PSC-MPP engraft at a higher level in NSG mice compared to cytokine-induced cells (10% >5 months), and selection increased engraftment (30%). Long-term engraftment and the myeloid-to-lymphoid ratio achieved with vascular niche induction is similar to levels achieved for cord blood MPP and up to 20-fold higher than hPSC-MPP engraftment. Our findings identify a previously underappreciated role for endothelial Notch ligands in PSC definitive hematopoiesis and production of long-term engrafting CD34+ cells and suggest they are critical for HSC emergence.
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| Overall design |
Transcriptome sequencing of Macaca nemestrina (Mn) iPSCs
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| Contributor(s) |
Gori J, Elemento O, Rafi S, Kiem H |
| Citation missing |
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| |
| Submission date |
Jan 04, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Olivier Elemento |
| E-mail(s) |
ole2001@med.cornell.edu
|
| Organization name |
WEILL MEDICAL COLLEGE OF CORNELL UNIV
|
| Street address |
1305 York Avenue
|
| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10021 |
| Country |
USA |
| |
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| Platforms (2) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL19597 |
Illumina HiSeq 2500 (Macaca nemestrina) |
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| Samples (5)
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| Relations |
| BioProject |
PRJNA271536 |
| SRA |
SRP051675 |
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