Comparison of ESC-derived and Primary-derived Tip-like Cell Transplants
Ontology highlight
ABSTRACT: The goal of this experiment was to determine whether transcriptionally similar ESC-derived and primary donor cells give rise to similar donor-derived cells following transplantation into bleomycin injured lungs.
Project description:The goal of this experiment was to determine whether transplantation of ESC-derived tip-like cells had any discernable impact on gene expression or clustering in non-epithelial cells.
Project description:We studied the effects of different stimuli on on the subcellular proteome of neurons differentiated from murine embryonic stem cells (ESC). We focused on the changes in the chromatin-bound fraction to elucidate specific differences in the gene regulatory machinery activated upon stimulation with Brain-derived neurotrophic factor (BDNF) or a general membrane-depolarization stimulus, potassium chloride (KCl).
Project description:The transplantation of ESCs into living recipients causes teratoma formation which accompanies with several biological reactions in both the transplanted cells and recipient. Co-injection of ESCs with somatic cells that influence donor-recipient homogeneity can affect transcriptional profile of transplanted ESCs. We investigated global gene expression of parental ESCs and ESC-like cells derived from teratomas which were formed by different injection conditions to find transcriptional differences according to donor-recipient homogeneity and somatic cell co-injection. Parental ESCs or teratoma-derived ESC-like cells from different treatments were retrieved for RNA extraction and hybridization on Affymetrix microarrays.
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.
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.
Project description:Differences of metabolism-related gene expression profiles in human ESCs and ESC-derived purified cardiomyocytes were analyzed and successfully identified. Human ESCs and ESC-derived purified cardiomyocytes were used for this experiment.
Project description:The transplantation of ESCs into living recipients causes teratoma formation which accompanies with several biological reactions in both the transplanted cells and recipient. Co-injection of ESCs with somatic cells that influence donor-recipient homogeneity can affect transcriptional profile of transplanted ESCs. We investigated global gene expression of parental ESCs and ESC-like cells derived from teratomas which were formed by different injection conditions to find transcriptional differences according to donor-recipient homogeneity and somatic cell co-injection.