This SuperSeries is composed of the SubSeries listed below.
Epigenetic chromatin states uniquely define the developmental plasticity of murine hematopoietic stem cells.
Specimen part
View SamplesThe major myeloid blood cell lineages, including erythrocytes, platelets, granulocytes and macrophages, are generated from hematopoietic stem cells (HSC) by differentiation through a series of increasingly more committed progenitor cells. Precise phenotypic identification and functional characterization of such intermediate progenitors has important consequences for understanding fundamental differentiation processes and is clinically relevant since such events become dysregulated in various disease settings, including leukemia. While previous studies have suggested a hierarchy for myeloid differentiation involving a common progenitor through which all myeloid lineages are derived, several recent studies have suggested that such a developmental intermediate might not be an absolute requirement. Here, we evaluated the functional in vitro and in vivo potentials of a range of prospectively isolated myeloid precursors with differential expression of CD150, Endoglin and CD41. Our studies reveal a complex hierarchy of myeloerythroid progenitors with distinct and developmentally restricted lineage potentials. Global gene expression signatures of these cellular subsets revealed expression patterns consistent with their functional capacities, while hierarchical clustering analysis provides details on their lineage relationships. These data challenge existing models of hematopoietic differentiation, by suggesting that progenitors of the innate and adaptive immune system in the adult separate late, and to a large extent, following the divergence of megakaryocytic/erythroid potential.
Elucidation of the phenotypic, functional, and molecular topography of a myeloerythroid progenitor cell hierarchy.
No sample metadata fields
View SamplesSomatic stem cells mediate tissue maintenance for the lifetime of an organism. Despite the well-established longevity that is a prerequisite for such function, accumulating data argue for compromised stem cell function with age. Identifying the mechanisms underlying age-dependent stem cell dysfunction is therefore key to understand the aging process.
No associated publication
Sex, Age, Specimen part
View SamplesAn investigation of the global gene expression signatures of murine hematopoietic stem cell differentiation during steady state hematopoiesis.
Epigenetic chromatin states uniquely define the developmental plasticity of murine hematopoietic stem cells.
Specimen part
View SamplesExpression profiling of CLP subfractions (with different potential to develop into T-cells) and B-cell progenitors.
No associated publication
No sample metadata fields
View SamplesThe homeobox (Hox) transcription factor HOXA10 has been implicated in regulation of hematopoietic cell fate. Here, using a transgenic mouse model where expression of HOXA10 is tightly regulated in a graded, doxycyclin-dependent manner we demonstrate that several key commitment steps in hematopoietic differentiation have distinctly different outcomes depending on the expression level of HOXA10. Similarly, HOXA10 regulates hematopoietic stem cell (HSC) proliferation in a dose dependent manner, since intermediate levels of HOXA10 generated a 4.5-fold increase in long-term repopulating capacity after 13 days of liquid culture, whereas high levels reduced proliferation of HSCs. Interestingly, the effects on HSC proliferation were associated with altered expression of several known regulators of stem cell self-renewal. Taken together, our findings reveal entirely novel functional and molecular aspects of HOXA10 in regulation of hematopoiesis and emphasize the need for tightly regulated production of HOX proteins in possible future applications of stem cell expansion.
No associated publication
No sample metadata fields
View SamplesGene expression was analyzed in intestinal epithelial cells of germ-free and wildtype mice.
A novel role for constitutively expressed epithelial-derived chemokines as antibacterial peptides in the intestinal mucosa.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Exploiting microRNA and mRNA profiles generated in vitro from carcinogen-exposed primary mouse hepatocytes for predicting in vivo genotoxicity and carcinogenicity.
Specimen part, Compound
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrating factor analysis and a transgenic mouse model to reveal a peripheral blood predictor of breast tumors.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Experimentally derived metastasis gene expression profile predicts recurrence and death in patients with colon cancer.
Sex, Age, Disease stage, Race
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