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Series GSE64644 Query DataSets for GSE64644
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.
Overall design Transcriptome sequencing of Macaca nemestrina (Mn) iPSCs
Contributor(s) Gori J, Elemento O, Rafi S, Kiem H
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Submission date Jan 04, 2015
Last update date May 15, 2019
Contact name Olivier Elemento
Street address 1305 York Avenue
City New York
State/province NY
ZIP/Postal code 10021
Country USA
Platforms (2)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL19597 Illumina HiSeq 2500 (Macaca nemestrina)
Samples (5)
GSM1576156 Day 8 EB
GSM1576157 Day 15 MPP + Cytokines
GSM1576158 Day 15 MPP+ EC
BioProject PRJNA271536
SRA SRP051675

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Supplementary file Size Download File type/resource
GSE64644_RAW.tar 550.0 Kb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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