ATAC-seq of uncultured CD112high and CD112low long-term(LT) human hematopoietic stem cells (HSC) from umbilical cord blood
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ABSTRACT:
PROVIDER: EGAS00001005121 | EGA |
REPOSITORIES: EGA
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Project description:We performed ATAC-sequencing to elucidate the chromatin accessibility that underlie the differential in vitro priming and regeneration phenotypes of CD112high and CD112low LT-HSC. Therefore, we prospectively isolated these subpopulations from 3 independent human umbilical cord blood pools and subjected to ATAC-sequencing directly. We show that distinct subsets of human LT-HSC respond differently to regeneration-mediated stress and that INKA1 governs these distinct stemness states where CD112low LT-HSC are marked by an alternative state of quiescence with high INKA1 and low H4K16ac preserving self-renewal and regenerative capacity upon successive rounds of regeneration-mediated stress.
2021-04-13 | GSE172005 | GEO
Project description:RNA-seq of uncultured CD112high and CD112low long-term(LT) human hematopoietic stem cells (HSC) and cultured and lentiviral transduced (CTRL, INKA1-OE) LT- and short-term HSC from umbilical cord blood We performed RNA-sequencing to elucidate the biological pathways (1) altered by INKA1 overexpression in LT-HSC and ST-HSC that may contribute to the induced transient restraint in generating proliferative hematopoietic output in vivo and in vitro; and (2) that underlie the differential in vitro priming and regeneration phenotypes of CD112high and CD112low LT-HSC. Therefore, we prospectively isolated indicated subpopulations from 3 independent human umbilical cord blood pools and subjected them either to RNA-sequencing directly or following culture, lentiviral transduction and purification of the transduced cell fractions. We show that distinct subsets of human LT-HSC respond differently to regeneration-mediated stress and that INKA1 governs these distinct stemness states where CD112low LT-HSC are marked by an alternative state of quiescence with high INKA1 preserving self-renewal and regenerative capacity upon successive rounds of regeneration-mediated stress.
2021-03-25 | GSE148883 | GEO
Project description:We performed RNA-sequencing to elucidate the biological pathways (1) altered by INKA1 overexpression in LT-HSC and ST-HSC that may contribute to the induced transient restraint in generating proliferative hematopoietic output in vivo and in vitro; and (2) that underlie the differential in vitro priming and regeneration phenotypes of CD112high and CD112low LT-HSC. Therefore, we prospectively isolated indicated subpopulations from 3 independent human umbilical cord blood pools and subjected them either to RNA-sequencing directly or following culture, lentiviral transduction and purification of the transduced cell fractions.
| EGAS00001004768 | EGA
Project description:Here we tracked transcriptional changes in LT, ST-HSC and MLP after transplantation into immunocompromised mice. We show that LT- and ST-HSC activate similar pathways upon transplantation but they modulate distinct sets of genes. Total RNA was obtained from flow-sorted populations of human LT-, ST-HSC and MLP isolated from cord blood or immunocompromised mice transplanted with human at hematopoeitic progenitors at different time points after transplantation.
2015-02-20 | E-GEOD-58299 | biostudies-arrayexpress
Project description:Here we tracked transcriptional changes in LT, ST-HSC and MLP after transplantation into immunocompromised mice. We show that LT- and ST-HSC activate similar pathways upon transplantation but they modulate distinct sets of genes.
2015-02-20 | GSE58299 | GEO
Project description:Long-term hematopoietic stem cells (LT-HSCs) are responsible for lifelong maintenance and regeneration of the blood system. Loss of LT-HSC function is a major contributor to decline in hematopoietic function with aging, leading to increased rate of infection, poor vaccination response, and increased risk of hematologic malignancies. While cellular and molecular hallmarks of LT-HSC aging have been defined1-3, a barrier to achieving the goal of extending healthy hematopoietic function into older age is the lack of understanding of the nature and timing of the initiating events that cause LT-HSC aging. Here we show that hallmarks of LT-HSC aging and decline in hematopoietic function accumulate by middle age in mice, and that the hematopoietic cell-extrinsic bone marrow (BM) microenvironment at middle age is necessary and sufficient to cause LT-HSC aging. Using unbiased transcriptome-based approaches, we identify decreased production of IGF1 by mesenchymal stromal cells (MSC) in the local middle-aged BM microenvironment as a factor causing LT-HSC aging and show that direct stimulation of middle-aged LT-HSCs with IGF1 rescues hallmarks of aging. Together, our study demonstrates that the initiating events causing LT-HSC and hematopoietic aging emerge by middle age and are caused by hematopoietic cell-extrinsic changes in the BM microenvironment. Declining IGF1 in the BM microenvironment at middle age represents a compelling target for intervention using prophylactic therapies to effectively extend healthspan and prevent decline in hematopoietic function during aging.
2020-02-08 | GSE144933 | GEO
Project description:Long-term hematopoietic stem cells (LT-HSCs) are responsible for lifelong maintenance and regeneration of the blood system. Loss of LT-HSC function is a major contributor to decline in hematopoietic function with aging, leading to increased rate of infection, poor vaccination response, and increased risk of hematologic malignancies. While cellular and molecular hallmarks of LT-HSC aging have been defined, a barrier to achieving the goal of extending healthy hematopoietic function into older age is the lack of understanding of the nature and timing of the initiating events that cause LT-HSC aging. Here we show that hallmarks of LT-HSC aging and decline in hematopoietic function accumulate by middle age in mice, and that the hematopoietic cell-extrinsic bone marrow (BM) microenvironment at middle age is necessary and sufficient to cause LT-HSC aging. Using unbiased transcriptome-based approaches, we identify decreased production of IGF1 by mesenchymal stromal cells (MSC) in the local middle-aged BM microenvironment as a factor causing LT-HSC aging and show that direct stimulation of middle-aged LT-HSCs with IGF1 rescues hallmarks of aging. Together, our study demonstrates that the initiating events causing LT-HSC and hematopoietic aging emerge by middle age and are caused by hematopoietic cell-extrinsic changes in the BM microenvironment. Declining IGF1 in the BM microenvironment at middle age represents a compelling target for intervention using prophylactic therapies to effectively extend healthspan and prevent decline in hematopoietic function during aging.
2021-01-12 | GSE164609 | GEO
Project description:Long-term hematopoietic stem cells (LT-HSCs) are responsible for lifelong maintenance and regeneration of the blood system. Loss of LT-HSC function is a major contributor to decline in hematopoietic function with aging, leading to increased rate of infection, poor vaccination response, and increased risk of hematologic malignancies. While cellular and molecular hallmarks of LT-HSC aging have been defined1-3, a barrier to achieving the goal of extending healthy hematopoietic function into older age is the lack of understanding of the nature and timing of the initiating events that cause LT-HSC aging. Here we show that hallmarks of LT-HSC aging and decline in hematopoietic function accumulate by middle age in mice, and that the hematopoietic cell-extrinsic bone marrow (BM) microenvironment at middle age is necessary and sufficient to cause LT-HSC aging. Using unbiased transcriptome-based approaches, we identify decreased production of IGF1 by mesenchymal stromal cells (MSC) in the local middle-aged BM microenvironment as a factor causing LT-HSC aging and show that direct stimulation of middle-aged LT-HSCs with IGF1 rescues hallmarks of aging. Together, our study demonstrates that the initiating events causing LT-HSC and hematopoietic aging emerge by middle age and are caused by hematopoietic cell-extrinsic changes in the BM microenvironment. Declining IGF1 in the BM microenvironment at middle age represents a compelling target for intervention using prophylactic therapies to effectively extend healthspan and prevent decline in hematopoietic function during aging.
2020-02-08 | GSE144934 | GEO
Project description:Long-term hematopoietic stem cells (LT-HSCs) are responsible for lifelong maintenance and regeneration of the blood system. Loss of LT-HSC function is a major contributor to decline in hematopoietic function with aging, leading to increased rate of infection, poor vaccination response, and increased risk of hematologic malignancies. While cellular and molecular hallmarks of LT-HSC aging have been defined1-3, a barrier to achieving the goal of extending healthy hematopoietic function into older age is the lack of understanding of the nature and timing of the initiating events that cause LT-HSC aging. Here we show that hallmarks of LT-HSC aging and decline in hematopoietic function accumulate by middle age in mice, and that the hematopoietic cell-extrinsic bone marrow (BM) microenvironment at middle age is necessary and sufficient to cause LT-HSC aging. Using unbiased transcriptome-based approaches, we identify decreased production of IGF1 by mesenchymal stromal cells (MSC) in the local middle-aged BM microenvironment as a factor causing LT-HSC aging and show that direct stimulation of middle-aged LT-HSCs with IGF1 rescues hallmarks of aging. Together, our study demonstrates that the initiating events causing LT-HSC and hematopoietic aging emerge by middle age and are caused by hematopoietic cell-extrinsic changes in the BM microenvironment. Declining IGF1 in the BM microenvironment at middle age represents a compelling target for intervention using prophylactic therapies to effectively extend healthspan and prevent decline in hematopoietic function during aging.
2020-07-01 | GSE151333 | GEO
Project description:Gene expression of LT-HSC (CD150+Flt3-lin-Sca-Kit+) hematopoietic stem cells from wild type mice was compared with LT-HSC from Cebpa knock-in mutant mice (K/L mutants). Fetal liver cells for each genotype were competitively transplanted into irradiant recipients. Donor-derived LT-HSC cells were isolated by FACS sorting of recipient bone marrow. Biological replicates of each (3 for wt, 2 for K/L) were generated and expression profiles were determined by hybridization to Affymetrix Moe430_2 arrays.
2009-11-03 | E-TABM-694 | biostudies-arrayexpress