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Series GSE71794 Query DataSets for GSE71794
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.
 
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.
 
Contributor(s) Lu Y, Cahan P
Citation(s) 28009288
Submission date Aug 06, 2015
Last update date Mar 22, 2019
Contact name Patrick Cahan
E-mail 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)
GSM1845528 ESC_1
GSM1845529 ESC_2
GSM1845530 ESC_3
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

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE71794_expDat_singleCell_YiFenLu_Aug_05_2015.xlsx 38.1 Mb (ftp)(http) XLSX
Raw data are available in SRA
Processed data is available on Series record

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