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Notch Activation Confers Enhanced Lymphoid Potential in Murine ESC/iPSC-derived HSC and Reconstitutes Adaptive Immunity In Vivo

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE71796 | GEO | 2016/12/21

SECONDARY ACCESSION(S): PRJNA292093

REPOSITORIES: GEO

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Notch Activation Confers Enhanced Lymphoid Potential in Murine ESC/iPSC-derived HSC and Reconstitutes Adaptive Immunity In Vivo [RNA-Seq]

Project description: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.

2016-12-21 | GSE71794 | GEO

Notch Activation Confers Enhanced Lymphoid Potential in Murine ESC/iPSC-derived HSC and Reconstitutes Adaptive Immunity In Vivo [Microarray expression]

2016-12-21 | GSE71793 | GEO