This SuperSeries is composed of the SubSeries listed below.
Targeted resequencing identifies PTCH1 as a major contributor to ocular developmental anomalies and extends the SOX2 regulatory network.
Specimen part, Time
View SamplesSOX2 is the main gene involved in anophthalmia. In order to identify genes regulated by SOX2 transcription factors (genes that could be good candidates to also be involved in ocular development), we studied transcriptomic profiles of murine genetically modified stem cells overexpressing the RAX gene (CCE-Rx cells) after transfection by a siRNA against SOX2 or a scramble siRNA.
Targeted resequencing identifies PTCH1 as a major contributor to ocular developmental anomalies and extends the SOX2 regulatory network.
Specimen part, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
GPI-80 defines self-renewal ability in hematopoietic stem cells during human development.
Specimen part
View SamplesAdvances in pluripotent stem cell and reprogramming technologies have given hope of generating hematopoietic stem cells (HSC) in culture. To succeed, greater understanding of the self-renewing HSC during human development is required. We discovered that glycophosphatidylinositol-anchored surface protein GPI-80 (Vanin 2) defines a distinct subpopulation of human fetal hematopoietic stem/progenitor cells (HSPC) with self-renewal ability. CD34+CD90+CD38-GPI-80+ HSPC were the sole population that maintained proliferative potential and undifferentiated state in bone marrow stroma co-culture, and engrafted in immunodeficient mice. GPI-80 expression also enabled tracking of HSC migration between human fetal hematopoietic niches. The most highly enriched surface protein in GPI-80+ HSPC as compared to their progeny was Integrin alpha-M (ITGAM), which in leukocytes cooperates with GPI-80 to support migration. Knockdown of either GPI-80 or ITGAM was sufficient to perturb undifferentiated HSPC in stroma co-culture. These findings indicate that human fetal HSC utilize common mechanisms with leukocytes for cell-cell interactions governing HSC self-renewal.
GPI-80 defines self-renewal ability in hematopoietic stem cells during human development.
Specimen part
View SamplesAdvances in pluripotent stem cell and reprogramming technologies have given hope of generating hematopoietic stem cells (HSC) in culture. To succeed, greater understanding of the self-renewing HSC during human development is required. We discovered that glycophosphatidylinositol-anchored surface protein GPI-80 (Vanin 2) defines a distinct subpopulation of human fetal hematopoietic stem/progenitor cells (HSPC) with self-renewal ability. CD34+CD90+CD38-GPI-80+ HSPC were the sole population that maintained proliferative potential and undifferentiated state in bone marrow stroma co-culture, and engrafted in immunodeficient mice. GPI-80 expression also enabled tracking of HSC migration between human fetal hematopoietic niches. The most highly enriched surface protein in GPI-80+ HSPC as compared to their progeny was Integrin alpha-M (ITGAM), which in leukocytes cooperates with GPI-80 to support migration. Knockdown of either GPI-80 or ITGAM was sufficient to perturb undifferentiated HSPC in stroma co-culture. These findings indicate that human fetal HSC utilize common mechanisms with leukocytes for cell-cell interactions governing HSC self-renewal.
GPI-80 defines self-renewal ability in hematopoietic stem cells during human development.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Medial HOXA genes demarcate haematopoietic stem cell fate during human development.
Specimen part
View SamplesThe derivation of functional, transplantable HSCs from an pluripotent stem cells in vitro holds great promise for clinical therapies, but is unachieved. In order to achieve full functionality of HSCs, it is vital to determine the extent to which PSCs can currently be differentiated to the HSC program in vitro and identify the remaining dysregulated genetic pathways.
Medial HOXA genes demarcate haematopoietic stem cell fate during human development.
Specimen part
View SamplesRA signalling regulated endothelial to hematopoietic transition and HSC generation. Overall design: EB- or FL-derived HSPC were profiled before (d0) or after (d6) 6 days of treatment with 0.2uM AM580 on OP9, and after 6 additional days of expandion of OP9 (d12) without treatment.
Medial HOXA genes demarcate haematopoietic stem cell fate during human development.
No sample metadata fields
View SamplesHOXA7 regulates FL-HSPC self-renewal in vitro and in vivo. We profiled EB-HSPCs after HOXA7 overexpression (EB-HOXA7), or with a control vector (EB-CTR), to assess the gene expression programs regulated by HOXA7. Overall design: CD34+CD38-CD43+CD90+ HSPCs were infected with lentiviral FUGW vector either empty (FUGW-GFP) or encoding HOXA7(FUGW-GFP-HOXA7) protein. Cells were expanded on op9 for 15 days and than sorted for GFP HSPC immunophenotype.
Medial HOXA genes demarcate haematopoietic stem cell fate during human development.
No sample metadata fields
View SamplesWe used microarray analysis to further our understanding of the mode of action of the well know caloric restriction mimetic rapamycin and the compound Allantoin first studied in the context of aging in this study. His work helps build on our understanding of potential caloric restriction mimetics predicted from our bioinformatic aproach of quering the Connectivity Map, a database of drug-induced gene expression profiles, using the transcriptional profile of CR to identify drugs that induce a similar or opposite gene expression profile.
A network pharmacology approach reveals new candidate caloric restriction mimetics in C. elegans.
Age, Specimen part
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