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| Status |
Public on Dec 21, 2016 |
| Title |
Notch Activation Confers Enhanced Lymphoid Potential in Murine ESC/iPSC-derived HSC and Reconstitutes Adaptive Immunity In Vivo [RNA-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Hematopoietic stem cell (HSC) transplantation has the potential to cure blood disorders but is limited by donor availability. Hence innovative approaches to engineer HSC are critically needed. HoxB4 over-expression in mouse embryonic stem cell-derived HSC (ESC-HSC) confers long-term engraftment, yet lacks efficient lymphogenesis. Transcriptome comparison of ESC-HSC versus embryo-derived HSC showed that ESC-HSC are deficient in expression programs activated by Notch. Therefore, we aim to improve ESC-HSC by further providing Notch signals through Notch1 intra-cellular domain transgene activation or by ligand stimulation. Here, we report that Notch-enhanced ESC-HSC (nESC-HSC) confer clonal multipotentiality with robust lymphopoiesis that endows adaptive immunity. Notably, nESC-HSC further evolve to a hybrid cell-type co-expressing gene regulatory networks of hematopoietic stem/progenitor cells and differentiated lineages at single-cell level that accounts for multipotentiality. Our work reveals a proof-of-concept model of HSC engineering by assembling self-renewing factor and lineage-guiding pathway into one product-cell that functionally recapitulate HSC in vivo.
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| |
|
| Overall design |
The gene expression of murine hematopoietic stem cells, ESC, and HSC-like cells derived from differentiation of embryonic stem cells and subsequently transplanted were determined by single cell RNA-Seq.
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| |
|
| Contributor(s) |
Lu Y, Cahan P |
| Citation(s) |
28009288 |
| |
| Submission date |
Aug 06, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Patrick Cahan |
| E-mail(s) |
patrick.cahan@jhmi.edu
|
| Organization name |
Johns Hopkins University School of Medicine
|
| Department |
ICE and Biomedical Engineering
|
| Lab |
Cahan Lab
|
| Street address |
733 North Broadway, MRB 653
|
| City |
Baltimore |
| State/province |
MD |
| ZIP/Postal code |
21205 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (316)
|
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| This SubSeries is part of SuperSeries: |
| GSE71796 |
Notch Activation Confers Enhanced Lymphoid Potential in Murine ESC/iPSC-derived HSC and Reconstitutes Adaptive Immunity In Vivo |
|
| Relations |
| BioProject |
PRJNA292097 |
| SRA |
SRP062111 |
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