Project description:Long-term hematopoietic stem cells (HSCs), short-term HSCs and multipotent progenitor cells (MPPs) were isolated from bone marrow of four mouse strains (WT, H19-deletion, Igf1r-deletion, and double-deletion) and expression profiled with RNAseq. The behavior of the transcriptomes, and in particular the imprinted genes, was analyzed to see what might be involved in maintaining quiescence of long-term stem cells, and how H19 and Igf1r affected the expression of imprinted genes. Transcriptional profiling data of the same cells have been deposited in ArrayExpress under accession number E-MTAB-1644 (http://wwwdev.ebi.ac.uk/arrayexpress/experiments/E-MTAB-1644/).
Project description:Murine long-term hematopoietic stem cells (HSCs), short-term HSCs and multipotent progenitor cells (MPPs) were isolated from bone marrow and expression profiled on Affy chips. The behavior of maternal-specific imprinting genes, particularly in the H19-Igf2 locus, was focused on, to see if any might be involved in maintaining quiescence of long-term stem cells.
Project description:Latexin is a hematopoietic stem cells (HSCs) and progenitor cells (HPCs) regulatory gene. Its deletion leads to the expansion of HSC and HPC population. The underlying mechanims are largely unknown. We therefore perfored microarrary analysis in HPCs with (Lxn-/-) and without (wild-type, WT) latexin deletion, and determined genes that were altered by latexin deletion. This led us to identify the molecular mechanims by which latexin regulates HSC function.
Project description:We isolated by fluorescence-activated cell sorting highly purified populations (long term hematopoietic stem cells (LT-HSCs), short term hematopoietic stem cells (ST-HSCs), multipotent progenitors (MPPs), common myeloid progenitor (CMPs), granulocyte and monocyte progenitors (GMPs), multilymphoid progenitors (MLPs), Myeloid-erythorid Progenitor (MEP), Granulocytes, Monocytes, B cells, T cells, Dendritic cells, Natural Killer cells and Erythrocyte Progenitors from 3 to 4 cord blood pools. We extracted RNA from 5K cells of each population and performed RNA-sequencing.
Project description:Here, we use single-cell RNA-Seq to examine variation between individual hematopoietic stem and progenitor cells from two mouse strains (C57BL/6 and DBA/2) as they age. We prepared libraries from long-term (LT-HSCs) (LSK CD150+CD48-), short-term hematopoietic stem cells (ST-HSCs) (LSK CD150-CD48-) and multipotent progenitors (MPPs) (LSK CD150+CD48+) from young (2-3 months) and old mice (22 months for C57BL/6 and 20 months for DBA/2). Population controls for each cell type and age were isolated by sorting processed in parallel.
Project description:Here we addressed the mRNA transcriptome of Long-Term Hematopoietic Stem Cells (LT-HSC) and Multipotent Progenitor (MPP) -3 and -4 purified from WT and Helios KO mice. By analyzing the differentially expressed genes among WT and KO condition we found that Helios deletion affects transcription mostly in the LT-HSC compartment and favor a megakaryocyte mRNA lineage priming at the expense of the lymphoid one.
Project description:Allogenic hematopoietic stem cell (HSC) transplantation is widely used for treatment of blood disorders to re-establish long-term multi-lineage hematopoiesis. Enhance self-renewal potential of progenitor population to support hematopoiesis offer an alternative and complementary approach to achieve similar therapeutic effects. Nup98-Hoxa10hd fusion gene (NA) has been shown to confer expansion, anti-stress response and engraftment competitiveness on HSC. However, whether the ectopic expression of NA in multipotent progenitors (MPPs) could enhance their self-renewal potential and confer long-term multi-lineage hematopoiesis remains unknown. In this study, we showed that ectopic expression in MPPs confer long-term multi-lineage hematopoiesis in recipient mice. We further showed that NA upregulated pathways of cell cycle regulation, epigenetic regulation and response to stress in MPPs. These molecular traits increased the self-renewal potential of NA MPPs, which resulting in production of lineage-maintaining committed progenitor cells. Transcriptome analysis of NA myeloid progenitors identified genes regulating hematopoiesis, homeostasis, phosphorylation. In summary, we show that ectopic expression of Nup98-Hoxa10hd fusion gene enhance self-renwal potential of MPPs thus confer long-term multilineage repopulating capacity on MPPs, offering promising means to involve MPPs to augment cell source in clinical transplantation settings.
Project description:Allogenic hematopoietic stem cell (HSC) transplantation is widely used for treatment of blood disorders to re-establish long-term multi-lineage hematopoiesis. Enhance self-renewal potential of progenitor population to support hematopoiesis offer an alternative and complementary approach to achieve similar or enhance therapeutic effects. Nup98-Hoxa10hd fusion gene (NA) has been shown to confer expansion, anti-stress response and engraftment competitiveness on HSC. However, whether the ectopic expression of NA in multipotent progenitors (MPPs) could enhance their self-renewal potential and confer long-term multi-lineage hematopoiesis remains unknown. In this study, we showed that ectopic expression in MPPs confer long-term multi-lineage hematopoiesis in recipient mice. We further showed that NA upregulated pathways of cell cycle regulation, epigenetic regulation and response to stress in MPPs. These molecular traits increased the self-renewal potential of NA MPPs, which resulting in production of lineage-maintaining committed progenitor cells. Transcriptome analysis of NA myeloid progenitors identified genes regulating hematopoiesis, homeostasis, phosphorylation. In summary, we show that ectopic expression of Nup98-Hoxa10hd fusion gene enhance self-renewal potential of MPPs thus confer long-term multi-lineage repopulating capacity on MPPs, offering promising means to involve MPPs to augment cell source in clinical transplantation settings.