Expression data from side population subfraction hematopoietic stem cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE16475 | GEO | 2010/03/01
SECONDARY ACCESSION(S): PRJNA116315
REPOSITORIES: GEO
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Project description:The traditional view of hematopoiesis has been that all the cells of the peripheral blood are the progeny of a unitary homogeneous pool of hematopoietic stem cells (HSCs). Recent evidence suggests that the hematopoietic system is actually maintained by a consortium of HSC subtypes with distinct functional characteristics. We show here that myeloid-biased HSCs (My-HSCs) and lymphoid-biased (Ly-HSCs) can be purified according to their capacity for Hoechst dye efflux in combination with canonical HSC markers. We used microarray expression profiling to determine the transcriptional profiles of myeloid-biased lower-SP HSCs and lymphoid-biased upper-SP HSCs Three biological replicates were analyzed for each HSC subpopulation. Lower-SP and upper-SP HSCs were purified from three pools of mice on separate days. HSCs were further purified with the addition of canonical HSC makers; Sca-1+ c-Kit+ Lineage-
2010-03-06 | E-GEOD-16475 | biostudies-arrayexpress
Project description:The hematopoietic stem cell (HSC) compartment includes lymphoid biased (Ly-HSCs) and myeloid biased (My-HSCs) subsets. Current models propose that the number of Ly-HSCs declines with age and this contributes to the diminution of lymphopoiesis that is a feature of aging. This view is based on a reduction in the frequency of Ly-HSCs in old bone marrow, but we now show that when total HSCs are taken into account, the number of Ly-HSCs is not reduced in old mice. We further demonstrate that old Ly-HSCs exhibit a normal capacity to produce lymphoid progenitors when removed from the bone marrow. However, the production of inflammatory cytokines is known to increase with age, and when Ly-HSCs are exposed to these mediators, lymphocyte production is blocked. We also demonstrate that old Ly-HSCs generate myeloid cells that phenotypically resemble those produced by old My-HSCs, a finding consistent with the myeloid biased gene expression pattern of old Ly-HSCs. These observations indicate that current models of how aging impacts the lymphopoietic potential of HSCs need to be revised and point to changes in the in vivo environment, rather than intrinsic changes in HSCs, as the principal cause of the reduced lymphopoiesis and increased myelopoiesis during aging.
2019-02-21 | GSE112769 | GEO
Project description:The hematopoietic stem cell (HSC) compartment is heterogeneous, yet our understanding of the identities of different HSC subtypes is limited. Here we show that platelet integrin CD41 (M-NM-1IIb), currently thought to only transiently mark fetal HSCs, is expressed on an adult HSC subtype that accumulates with age. CD41+ HSCs were largely quiescent and exhibited myeloerythroid and megakaryocyte gene priming, governed by Gata1, whereas CD41- HSCs were more proliferative and exhibited lymphoid gene priming. When isolated without the use of blocking antibodies, CD41+ HSCs possessed long-term repopulation capacity upon serial transplantations and showed a marked myeloid-bias compared to CD41-HSCs, which yielded a more lymphoid-biased progeny. CD41-knockout mice displayed multilineage hematopoietic defects coupled with decreased quiescence and survival of HSCs, suggesting that CD41 is functionally relevant for HSC maintenance and hematopoietic homeostasis. Transplantation experiments indicated that CD41-KO associated defects are long-term transplantable and HSC-derived, and in part mediated through the loss of platelet mass leading to decreases in HSC exposure to important platelet released cytokines, such as TGFM-NM-21. In summary, our data provide a novel marker to identify a myeloid-biased HSC subtype that becomes prevalent with age, and highlights the dogma of HSC regulation by their progeny. For microarray analysis, 1000 HSCs were FACS sorted from pools of 4-5 mice directly into lysis buffer, RNA extracted and whole transcript amplification was performed as previously described (Gonzalez-Roca E, Garcia-Albeniz X, Rodriguez-Mulero S, Gomis RR, Kornacker K, Auer H. Accurate expression profiling of very small cell populations. PLoS One. 2010;5:e14418.)
2013-04-11 | E-GEOD-45561 | biostudies-arrayexpress
Project description:The hematopoietic stem cell (HSC) compartment is heterogeneous, yet our understanding of the identities of different HSC subtypes is limited. Here we show that platelet integrin CD41 (αIIb), currently thought to only transiently mark fetal HSCs, is expressed on an adult HSC subtype that accumulates with age. CD41+ HSCs were largely quiescent and exhibited myeloerythroid and megakaryocyte gene priming, governed by Gata1, whereas CD41- HSCs were more proliferative and exhibited lymphoid gene priming. When isolated without the use of blocking antibodies, CD41+ HSCs possessed long-term repopulation capacity upon serial transplantations and showed a marked myeloid-bias compared to CD41-HSCs, which yielded a more lymphoid-biased progeny. CD41-knockout mice displayed multilineage hematopoietic defects coupled with decreased quiescence and survival of HSCs, suggesting that CD41 is functionally relevant for HSC maintenance and hematopoietic homeostasis. Transplantation experiments indicated that CD41-KO associated defects are long-term transplantable and HSC-derived, and in part mediated through the loss of platelet mass leading to decreases in HSC exposure to important platelet released cytokines, such as TGFβ1. In summary, our data provide a novel marker to identify a myeloid-biased HSC subtype that becomes prevalent with age, and highlights the dogma of HSC regulation by their progeny.
2013-04-11 | GSE45561 | GEO
Project description:Array analysis of My-bi and Ly-bi HSC identifies candidate molecules for myeloid-bias. Collectively the data show that HSC in adults are largely epigenetically fixed in differentiation and self-renewal behavior. A direct examination of the epigenetic mechanisms that imprint HSC is difficult. However, an indirect way of assessing the effects of epigenetic imprinting is to look for the expressed gene programs of different types of HSC. Therefore, we performed an array analysis in collaboration with Dr. Michael Cooke. My-bi and Ly-bi HSC were identified in clonally repopulated hosts. The analysis returned 218 differentially expressed genes (M-bM-^IM-% Log2 M-bM-^IM-%2, p< 0.05) of which 36 were found to be overexpressed in My-bi HSC and the rest was overexpressed in Ly-bi HSC (Appendix A). There was no difference in expression levels for genes known to be involved in fate decisions during differentiation. This agrees well with our data that lineage bias is a stable function of a HSC, and does not reflect a differentiated type of cell. Gene expression profiles of myeloid-biased (My-bi) and lymphoid-biased (Ly-bi) stem cells were analyzed. Clonally repopulated hosts were generated by limiting dilution of bone marrow into ablated hosts and lineage bias was determined. Single My-bi (Tenor) and Ly-bi (Mort) repopulated hosts were sacrificed and Donor type HSC were enriched for Sca-1+, Lin- cells. Two technical replicates of RNA extract were run from each clone.
2013-05-01 | E-GEOD-41702 | biostudies-arrayexpress
Project description:MTD project_description Inflammation and decreased stem cell function characterize organism aging, yet the relationship between these factors remains incompletely understood. This study shows that aged hematopoietic stem and progenitor cells exhibit increased ground-stage NF-κB activity, which enhances their responsiveness to undergo differentiation and loss of self-renewal in response to inflammation. The study identifies Rad21/cohesin as a critical mediator of NF-κB signals, by increasing chromatin accessibility of inter-/intra-genic and enhancer regions. Rad21/NF-κB are required for normal differentiation, but limit self-renewal of hematopoietic stem cells (HSCs) during aging and inflammation in an NF-κB dependent manner. HSCs from aged mice fail to downregulate Rad21/cohesin and inflammation/differentiation inducing signals in the resolution phase after acute inflammation. and The inhibition of cohesin/NF-κB is sufficient to revert the hypersensitivity of aged HSPCs to inflammation-induced differentiation. During aging, myeloid-biased HSCs with disrupted and naturally occurring reduced expression of Rad21/cohesin are increasingly selected over lymphoid-biased HSCs. Together, Rad21/cohesin mediated NF-κB signaling limits HSPC function during aging and selects for cohesin deficient HSCs with myeloid skewed differentiation.
2018-11-28 | PXD011537 | Pride
Project description:Side population (SP) cells are identified based on their capacity to efflux of the fluorescent dye Hoechst 33342, and are enriched for hematopoietic stem cells (HSCs) in mammalian bone marrow. We recently demonstrated that SP cells were present in the teleost kidney, the main hematopoietic organ in teleosts, and were enriched for HSCs. In this analysis, to identify the regulated genes in teleost HSCs, gene expression analysis of zebrafish kidney SP cells were performed using the GeneChip Zebrafish Genome Array. Experiment Overall Design: Based on their Hoechst fluorescence intensity, lymphoid cells (FS-low, SS-low) from zebrafish kidney were subdivided into SP and MP populations (referred to as âzSPâ and âzMPâ). To minimize the biological variability, 20 zebrafish were used for 3 independent cell sorting experiments and lysates from these 3 experiments were pooled by cell type. Each RNA sample was split into two aliquots and used for amplification, labeling, and hybridization to independent arrays.
2008-10-26 | E-GEOD-12955 | biostudies-arrayexpress
Project description:To study the effect of CD27 triggering on HSC biology Ageing of the hematopoietic stem cell (HSC) compartment is characterized by an accumulation of less productive HSCs with impaired lymphoid differentiation capacity, which contributes to age-dependent hematological abnormalities including anemia, myeloproliferative disorders and a decline in adaptive immunity. Since HSCs express the costimulatory receptor CD27 and because inflammation has been associated with HSC ageing, we investigated the effect of stimulation of CD27 by its inflammatory ligand CD70 on HSC maintenance. We found that CD27-triggering during CD70-driven immune activation in young mice enhances HSC self-renewal, leading to accumulation of HSCs to levels comparable with old control mice. These findings indicate that CD27-signaling accelerates HSC ageing, which is supported by the observation that CD27-triggering negatively affects HSC differentiation to the lymphoid lineage and increases myeloid differentiation. This functional change was mirrored by a corresponding difference in gene expression, as microarray analysis indicated that CD27-triggered HSCs have a strongly myeloid-biased gene signature. CD27 signaling also induced enrichment of genes associated with biological processes involved in cellular responses to DNA damage/repair and reactive oxygen species (ROS), which are associated with HSC ageing and related to increased proliferation. Therefore, we postulate that CD27 triggering during chronic inflammation contributes directly to ageing of the hematopoietic compartment.
2014-12-31 | GSE31574 | GEO
Project description:Loss of immune function and an increased incidence of myeloid leukemia are two of the most clinically significant consequences of aging of the hematopoietic system. To better understand the mechanisms underlying hematopoietic aging, we evaluated the cell intrinsic functional and molecular properties of highly purified long-term hematopoietic stem cells (LT-HSCs) from young and old mice. We found that LT-HSC aging was accompanied by cell autonomous changes, including increased stem cell self-renewal, differential capacity to generate committed myeloid and lymphoid progenitors, and diminished lymphoid potential. Expression profiling revealed that LT-HSC aging was accompanied by the systemic down-regulation of genes mediating lymphoid specification and function and up-regulation of genes involved in specifying myeloid fate and function. Moreover, LT-HSCs from old mice expressed elevated levels of many genes involved in leukemic transformation. These data support a model in which age-dependent alterations in gene expression at the stem cell level presage downstream developmental potential and thereby contribute to age-dependent immune decline, and perhaps also to the increased incidence of leukemia in the elderly.
2005-08-16 | E-SMDB-3450 | biostudies-arrayexpress
Project description:Side population (SP) cells are identified based on their capacity to efflux of the fluorescent dye Hoechst 33342, and are enriched for hematopoietic stem cells (HSCs) in mammalian bone marrow. We recently demonstrated that SP cells were present in the teleost kidney, the main hematopoietic organ in teleosts, and were enriched for HSCs. In this analysis, to identify the regulated genes in teleost HSCs, gene expression analysis of zebrafish kidney SP cells were performed using the GeneChip Zebrafish Genome Array.
2008-10-10 | GSE12955 | GEO