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Effect of aryl hydrocarbon receptor (Ahr) gene knockout on expression profiles of murine hematopoietic stem cells

ABSTRACT: As part of a study of the role of the aryl hydrocarbon receptor (Ahr) in maintenance and senescence of hematopoietic stem cells (HSC), global gene expression profiling was done with HSC isolated from Ahr-knockout and wild-type mice. HSC from young-adult (8 wk old) AhR-KO mice had changes in expression of many genes related to HSC maintenance, consistent with the phenotype observed in aging Ahr-KO mice: decreased survival rate, splenomegaly, increased circulating white blood cells, hematopoietic cell accumulation in tissues, anemia, increased numbers of stem/progenitor and lineage-committed cells in bone marrow, decreased erythroid progenitor cells in bone marrow, and decreased self-renewal capacity of HSC.

ORGANISM(S): Mus musculus

PROVIDER: GSE46976 | GEO | 2013/11/08

SECONDARY ACCESSION(S): PRJNA203200

REPOSITORIES: GEO

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Effect of aryl hydrocarbon receptor (Ahr) gene knockout on expression profiles of murine hematopoietic stem cells

Project description:As part of a study of the role of the aryl hydrocarbon receptor (Ahr) in maintenance and senescence of hematopoietic stem cells (HSC), global gene expression profiling was done with HSC isolated from Ahr-knockout and wild-type mice. HSC from young-adult (8 wk old) AhR-KO mice had changes in expression of many genes related to HSC maintenance, consistent with the phenotype observed in aging Ahr-KO mice: decreased survival rate, splenomegaly, increased circulating white blood cells, hematopoietic cell accumulation in tissues, anemia, increased numbers of stem/progenitor and lineage-committed cells in bone marrow, decreased erythroid progenitor cells in bone marrow, and decreased self-renewal capacity of HSC. 7 samples: 3 Ahr knockout, 4 wild-type

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Project description:As part of a study of the role of the aryl hydrocarbon receptor (Ahr) in maintenance and senescence of hematopoietic stem cells (HSC), global gene expression profiling was done with HSC isolated from 18-month-old Ahr-knockout and wild-type mice. HSC from aged AhR-KO mice had changes in expression of many genes related to HSC maintenance, consistent with the phenotype observed in aging Ahr-KO mice: decreased survival rate, splenomegaly, increased circulating white blood cells, hematopoietic cell accumulation in tissues, anemia, increased numbers of stem/progenitor and lineage-committed cells in bone marrow, decreased erythroid progenitor cells in bone marrow, and decreased self-renewal capacity of HSC. 10 samples: 5 Ahr knockout, 5 wild-type

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Project description:As part of a study of the role of the aryl hydrocarbon receptor (Ahr) in maintenance and senescence of hematopoietic stem cells (HSC), global gene expression profiling was done with HSC isolated from 18-month-old Ahr-knockout and wild-type mice. HSC from aged AhR-KO mice had changes in expression of many genes related to HSC maintenance, consistent with the phenotype observed in aging Ahr-KO mice: decreased survival rate, splenomegaly, increased circulating white blood cells, hematopoietic cell accumulation in tissues, anemia, increased numbers of stem/progenitor and lineage-committed cells in bone marrow, decreased erythroid progenitor cells in bone marrow, and decreased self-renewal capacity of HSC.

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Effect of bone marrow-specific aryl hydrocarbon receptor (Ahr) gene knockout on expression profiles of hematopoietic stem cells from young and old mice.

Project description:As part of a study of the role of the aryl hydrocarbon receptor (Ahr) in maintenance and senescence of hematopoietic stem cells (HSC), global gene expression profiling was done with HSC isolated from bone marrow restricted conditional Ahr-knockout and AhR floxed mice. HSC from young-adult (8 wk old) cAhR-KO mice had changes in expression of many genes related to HSC maintenance, consistent with the phenotype observed in Ahr-KO mice. Aged cAhR-KO mice (18 months old) also displayed alterations in peripheral white blood cell counts, serial repopulation potential and levels of ROS in bone marrow cells, consistent with previous observations on the role of AhR in the hematopoietic system. 22 samples: 5 young Ahr knockout, 6 old Ahr knockout, 5 young floxed Ahr, 6 old floxed Ahr

2016-06-30 | E-GEOD-76276 | biostudies-arrayexpress

Effect of bone marrow-specific aryl hydrocarbon receptor (Ahr) gene knockout on expression profiles of hematopoietic stem cells from young and old mice.

Project description:As part of a study of the role of the aryl hydrocarbon receptor (Ahr) in maintenance and senescence of hematopoietic stem cells (HSC), global gene expression profiling was done with HSC isolated from bone marrow restricted conditional Ahr-knockout and AhR floxed mice. HSC from young-adult (8 wk old) cAhR-KO mice had changes in expression of many genes related to HSC maintenance, consistent with the phenotype observed in Ahr-KO mice. Aged cAhR-KO mice (18 months old) also displayed alterations in peripheral white blood cell counts, serial repopulation potential and levels of ROS in bone marrow cells, consistent with previous observations on the role of AhR in the hematopoietic system.

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Project description:In the human hematopoietic system, aging is associated with decreased bone marrow cellularity, decreased adaptive immune system function, and increased incidence of anemia and other hematological disorders and malignancies. Recent studies in mice suggest that changes within the hematopoietic stem cell (HSC) population during aging contribute significantly to the manifestation of these age-associated hematopoietic pathologies. While the mouse HSC population has been shown to change both quantitatively and functionally with age, changes in the human HSC and progenitor cell populations during aging have not yet been characterized. Gene expression profiling revealed that aged human HSC transcriptionally up-regulate genes associated with cell cycle, myeloid lineage specification, and myeloid malignancies. These age-associated alterations in the frequency, function, and gene expression profile of human HSC are significantly similar to those changes observed in mouse HSC, suggesting that hematopoietic aging is an evolutionarily conserved process. In order to elucidate the properties of an aged human hematopoietic system that may predispose to age-associated hematopoietic dysfunction, we evaluated HSC and other hematopoietic progenitor populations from healthy, hematologically normal young and elderly human bone marrow samples. We found that aged human HSC increase in frequency, are less quiescent, and exhibit myeloid-biased differentiation potential compared to young HSC.

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Probing secretome of hematopoietic and mesenchymal stem cell interactions in single and co-cultures

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