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| Status |
Public on Oct 30, 2012 |
| Title |
Efficient direct reprogramming of c-Kit− mature amniotic cells into endothelial cells by ETS factors and TGFβ suppression |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
ETS transcription factors ETV2, FLI1 and ERG1 specify pluripotent stem cells into endothelial cells (PSC-ECs). However, these PSC-ECs are unstable and often drift towards non-vascular cell fates. We show that human mid-gestation c-Kit- lineage-committed amniotic cells (ACs) can be reprogrammed into induced vascular endothelial cells (rAC-VECs). Transient ETV2 expression in ACs generated immature iVECs, while co-expression with FLI1/ERG1 endowed rAC-VECs with a vascular repertoire and morphology matching mature ECs. Brief TGFb-inhibition functionalizes VEGFR2 signaling, augmenting specification of ACs into rAC-VECs. Genome-wide transcriptional analyses showed that rAC-VECs are similar to adult ECs in which vascular-specific genes are expressed and non-vascular genes are silenced. Functionally, rAC-VECs form stable vasculature in Matrigel plugs and regenerating livers. Thus, short-term ETV2 expression and TGFb-inhibition along with constitutive ERG1/FLI1 co-expression reprogram mature ACs into generic rAC-VECs with clinical-scale expansion potential. Public banking of HLA-typed rAC-VECs would establish a vascular inventory for treatment of genetically diverse disorders.
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| |
|
| Overall design |
Transcriptome sequencing of clonal and non-clonal rAC-VECs, HUVECs, LSECs, CD34+/Lin-, BMS
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| |
|
| Contributor(s) |
Ginsberg M, Elemento O, Rafii S |
| Citation(s) |
23084400 |
| Submission date |
Aug 22, 2012 |
| 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 |
| |
|
| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (11)
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| Relations |
| BioProject |
PRJNA173424 |
| SRA |
SRP015439 |
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