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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jul 11, 2014 |
| Title |
Reprogramming of Endothelium Into Hematopoietic Progenitors by Defined Factors and Vascular Induction |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Generation of abundant engraftable hematopoietic cells from autologous tissues promises new therapies for hematologic diseases. Differentiation of pluripotent stem cells into hematopoietic cells results in emergence of cells that have poor engraftment potential. To circumvent this hurdle, we have devised a vascular niche model to phenocopy the developmental microenvironment of hemogenic cells thereby enabling direct transcriptional reprogramming of human endothelial cells (ECs) into hematopoietic cells. In this approach, transduction of human umbilical vein ECs (HUVECs) or adult human dermal microvascular ECs (hDMECs) with transcription factors (TFs), FOSB, GFI1, RUNX1, and SPI1 (FGRS) and induction with a instructive vascular niche feeder layer in a xenobiotic- and serum-free microenvironment results in generation of long-term engraftable hematopoietic multilineage progenitors (rEC-HMLPs). The rEC-HMLPs had robust proliferative and multilineage colony forming units (CFU) potential, including granulocytic/monocytic, megakaryocytic, erythroid and lymphoid lineages. When transplanted, hDMEC-derived rEC-HMLPs were capable of long-term multilineage primary and secondary hematopoietic engraftment. A subset of engrafted rEC-HMLPs phenotypically and functionally resembled cord blood cells. By conditionally expressing the FGRS TFs, we further optimized reprogramming of ECs into rEC-HMLPs manifesting features of self-renewing multi-potent progenitor populations (MPPs). Our approach replicates critical aspects of hematopoietic development and essential role of vascular niche induction in orchestrating hematopoietic specification and may prove useful for engineering autologous engraftable hematopoietic cells for treatment of inherited and acquired blood disorders. .
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| Overall design |
Transcriptome sequencing of rEC-HMLPs, hDMECs, HUVECs and other cell types
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| Contributor(s) |
Sandler V, Lis R, Elemento O, Rafii S |
| Citation(s) |
25030167, 29217753 |
| Submission date |
May 14, 2014 |
| Last update date |
Jul 08, 2019 |
| Contact name |
Olivier Elemento |
| E-mail(s) |
ole2001@med.cornell.edu
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| Organization name |
WEILL MEDICAL COLLEGE OF CORNELL UNIV
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| Street address |
1305 York Avenue
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10021 |
| Country |
USA |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA247475 |
| SRA |
SRP041988 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE57662_RAW.tar |
2.7 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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