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Microarray analysis of IdHP cells compared to LKS, Control ProB and E2A-/- progenitors

ABSTRACT: Self-renewal potential and multipotency are hallmarks of the stem cell1-3. It is generally conceived that acquisition of such a stemness requires rejuvenation of somatic cells through reprogramming of genetic and epigenetic status. We show here that a simple blockage of cell differentiation is sufficient to make stem cells. By over-expression of transcriptional repressor Id3 in murine hematopoitic progenitor cells and cultivation of these cells in B cell induction conditions, cells exhibit developmental arrest and enter a self-renewal cycle. These cells can be maintained in vitro almost limitlessly, and the long-term cultured cells exhibited robust multi-lineage reconstitution when transferred into irradiated mice. These cells can be cloned and re-expanded with 50% of plating efficiency, indicating that virtually all cells are self-renewing. Equivalent progenitors were produced from progenitors in human cord blood. Thus produced stem cells will be useful as the source of cells for immune cell therapy.

ORGANISM(S): Mus musculus

PROVIDER: GSE46158 | GEO | 2014/06/01

SECONDARY ACCESSION(S): PRJNA197388

REPOSITORIES: GEO

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Microarray analysis of IdHP cells compared to LKS, Control ProB and E2A-/- progenitors

Project description:Self-renewal potential and multipotency are hallmarks of the stem cell1-3. It is generally conceived that acquisition of such a stemness requires rejuvenation of somatic cells through reprogramming of genetic and epigenetic status. We show here that a simple blockage of cell differentiation is sufficient to make stem cells. By over-expression of transcriptional repressor Id3 in murine hematopoitic progenitor cells and cultivation of these cells in B cell induction conditions, cells exhibit developmental arrest and enter a self-renewal cycle. These cells can be maintained in vitro almost limitlessly, and the long-term cultured cells exhibited robust multi-lineage reconstitution when transferred into irradiated mice. These cells can be cloned and re-expanded with 50% of plating efficiency, indicating that virtually all cells are self-renewing. Equivalent progenitors were produced from progenitors in human cord blood. Thus produced stem cells will be useful as the source of cells for immune cell therapy. Four samples

2014-06-01 | E-GEOD-46158 | biostudies-arrayexpress

miR-125a Confers Multi-Lineage Long-Term Repopulating Stem Cell Activity to Murine and Human Hematopoietic Progenitors

Project description:Umbilical cord blood (CB) is a non-invasive, convenient and broadly used source of hematopoietic stem cells (HSCs) for allogeneic stem cell transplantation. However, limiting numbers of HSCs remain a major constraint for its clinical application. One feasible option would be to expand HSCs to improve therapeutic outcome, however available protocols and the molecular mechanisms governing the self-renewal of HSC are unclear. Here we show that ectopic expression of a single miRNA, miR-125a, in purified murine and human multipotent progenitors (MPP) resulted in increased self-renewal and robust long-term multi-lineage repopulation in transplanted recipient mice. Using quantitative proteomics and Western blot analysis, we identified a restricted set of miR-125a targets which revealed the involvement of the MAP kinase signaling pathway in conferring long-term repopulating capacity to multipotent progenitors in human and mice. Our findings offer the innovative potential to use MPP with enhanced self-renewal activity to augment limited sources of HSC to improve clinical protocols.

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Transcription profiling of human HSC enriched population, common myeloid progenitors, granulocyte macrophage progenitors, megakaryocyte progenitors, and leukemia stem cells (leukemic-GMP) reveals MLL-AF9 transforms committed progenitors to leukemia stem cells by activation of a stem cell program (expt 2)

Project description:Leukemias and other cancers possess a rare population of cells capable of self-renewal, and eradication of these cancer stem cells is likely necessary for long-term cancer-free survival. Given that both normal and cancer stem cells are capable of self-renewal the extent to which cancer stem cells resemble normal tissue stem cells is a critical issue if targeted therapies are to be developed. We introduced the MLL-AF9 fusion protein encoded by the t(9;11)(p22;q23) found in human acute myelogenous leukemia (AML) into murine committed granulocyte-macrophage progenitors (GMP). The resultant leukemias contained cells with an immunophenotype similar to normal GMP that were highly enriched for leukemia stem cells (LSC). Detailed gene expression comparisons between normal hematopoietic stem cells (HSC), committed progenitors, and the LSC population demonstrated the LSC were globally more similar to the normal GMP than any other population. However, a subset of genes highly expressed in normal stem cells was re-activated in the LSC. These data demonstrate LSC can be generated from committed progenitors without widespread reprogramming of gene expression, and a leukemia self-renewal associated signature is activated in the process. Our findings define progression from normal hematopoietic progenitor to leukemia stem cell, and suggest that targeting a self-renewal program expressed in an abnormal context may be possible. Experiment Overall Design: A normal HSC enriched population, common myeloid progenitors, granulocyte macrophage progenitors, megakaryocyte progenitors, and leukemia stem cells (leukemic-GMP) were isolated and labeled RNA was hybridzed to Affymetrix microarrays

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Transcription profiling of isolated granulocyte macrophage progenitors were incubated with a retrovirus that expressed either GFP or MLL-AF9 and GFP reveals MLL-AF9 transforms committed progenitors to leukemia stem cells by activation of a stem cell program (expt 1)

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