|
| Status |
Public on May 18, 2017 |
| Title |
Conversion of adult endothelium to immunocompetent haematopoietic stem cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Developmental pathways that orchestrate the fleeting transition of endothelial cells into haematopoietic stem cells remain undefined. Here we demonstrate a tractable approach for fully reprogramming adult mouse endothelial cells to haematopoietic stem cells (rEC-HSCs) through transient expression of the transcription-factor-encoding genes Fosb, Gfi1, Runx1, and Spi1 (collectively denoted hereafter as FGRS) and vascular-niche-derived angiocrine factors. The induction phase (days 0-8) of conversion is initiated by expression of FGRS in mature endothelial cells, which results in endogenous Runx1 expression. During the specification phase (days 8-20), RUNX1+ FGRS-transduced endothelial cells commit to a haematopoietic fate, yielding rEC-HSCs that no longer require FGRS expression. The vascular niche drives a robust self-renewal and expansion phase of rEC-HSCs (days 20-28). rEC-HSCs have a transcriptome and long-term self-renewal capacity similar to those of adult haematopoietic stem cells, and can be used for clonal engraftment and serial primary and secondary multi-lineage reconstitution, including antigen-dependent adaptive immune function. Inhibition of TGF? and CXCR7 or activation of BMP and CXCR4 signalling enhanced generation of rEC-HSCs. Pluripotency-independent conversion of endothelial cells into autologous authentic engraftable haematopoietic stem cells could aid treatment of haematological disorders.
|
| |
|
| Overall design |
Expression profiling by high throughput sequencing data; GPL17021 Illumina HiSeq 2500 (Mus musculus)
|
| |
|
| Contributor(s) |
Lis R, Kunar B, Rafii S |
| Citation(s) |
28514438 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 DK095039 |
Identification of vascular inductive signals in liver regeneration |
WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY |
Shahin Rafii |
| R01 HL097797 |
Contribution of the vascular niche to the hematopoietic reconstitution. |
WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY |
Shahin Rafii |
| R01 HL115128 |
Evaluation of Pluripotent Stem Cell-Derived Blood Cells in Nonhuman Primate Model |
FRED HUTCHINSON CANCER RESEARCH CENTER |
Shahin Rafii |
| R01 HL119872 |
Identification of vascular-derived signals for alveolar lung repair |
WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY |
Shahin Rafii |
| R01 HL128158 |
Deciphering molecular determinants of vascular heterogeneity for organ repair |
WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY |
Shahin Rafii |
| T32 HD060600 |
Training Program in Developmental and Stem Cell Biology |
WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY |
Heidi Stuhlmann |
|
| |
| Submission date |
Oct 17, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Balvir Kunar, Jr. |
| E-mail(s) |
bak2010@med.cornell.edu
|
| Organization name |
Weill Cornell Medical College
|
| Department |
Regenerative Medicine; Physiology, Biophysics, & Systems Biology
|
| Lab |
Shahin Rafii, M.D.
|
| Street address |
1300 York Ave
|
| City |
New York City |
| State/province |
New York |
| ZIP/Postal code |
10065 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (30)
|
|
| Relations |
| BioProject |
PRJNA348758 |
| SRA |
SRP091674 |
Less...
More...