Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single Cell Transcriptomic Analysis Demonstrating Oxygen Dependence of Human Hematopoietic Stem and Progenitor Cells

ABSTRACT: Hematopoietic stem and progenitor cells support a lifetime supply of blood and immune cells, can become neoplastic when dysregulated, and constitute a powerful cell therapy vehicle for hematologic diseases. We demonstrated that human hematopoietic cell numbers, growth, biochemical properties, and functional potency is affected by variation in physiologically and clinically relevant local oxygen tensions. Lineage defined progenitor cells showed increased expansion in high oxygen, while primitive cells and those with in vivo potency were maintained at higher frequencies in low physiologic oxygen. Here we present a novel hematopoietic cell oxygen-dependent single cell transcriptomic profile to determine changes in gene expression induced by exposure to various physiologically relevent oxygen tensions.

ORGANISM(S): Homo sapiens

PROVIDER: GSE322748 | GEO | 2026/07/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Multiple oxygen tension environments reveal diverse patterns of transcriptional regulation in primary astrocytes

Project description:The central nervous system normally functions at O2 levels which would be regarded as hypoxic by most other tissues. However, most in vitro studies of neurons and astrocytes are conducted under hyperoxic conditions without consideration of O2-dependent cellular adaptation. We analyzed the reactivity of astrocytes to 1, 4 and 9% O2 tensions compared to the cell culture standard of 20% O2, to investigate their ability to sense and translate this O2 information to transcriptional activity. Variance of ambient O2 tension for rat astrocytes resulted in profound changes in ribosomal activity, cytoskeletal and energy-regulatory mechanisms and cytokine-related signaling. Clustering of transcriptional regulation patterns revealed four distinct response pattern groups that directionally pivoted around the 4% O2 tension, or demonstrated coherent ascending/decreasing gene expression patterns in response to diverse oxygen tensions. Immune response and cell cycle/cancer-related signaling pathway transcriptomic subsets were significantly activated with increasing hypoxia, whilst hemostatic and cardiovascular signaling mechanisms were attenuated with increasing hypoxia. Our data indicate that variant O2 tensions induce specific and physiologically-focused transcript regulation patterns that may underpin important physiological mechanisms that connect higher neurological activity to astrocytic function and ambient oxygen environments. These strongly defined patterns demonstrate a strong bias for physiological transcript programs to pivot around the 4% O2 tension, while uni-modal programs that do not, appear more related to pathological actions. The functional interaction of these transcriptional ‘programs’ may serve to regulate the dynamic vascular responsivity of the central nervous system during periods of stress or heightened activity.

2012-09-20 | GSE29296 | GEO

In Vivo Protein Turnover Rates in Varying Oxygen Tensions Nominate MYBBP1A as a Novel Mediator of the Hyperoxia Response

Project description:Oxygen deprivation and excess are both toxic to mammals. Thus, the body’s ability to adapt to varying oxygen tensions is critical for survival. While the transcriptional response to acute hypoxia has been well-studied, the post-translational effects of hypoxia and hyperoxia have been underexplored. In this study, we systematically investigate protein turnover rates in mouse heart, lung, and brain under different inhaled oxygen tensions. We find that the lung proteome is the most responsive to changes in oxygen tension, likely due to the direct exposure of alveoli to inhaled oxygen. In particular, several extracellular matrix (ECM) proteins such as collagens and laminins, are stabilized in the lung under both hypoxia and hyperoxia, suggesting their post-translational regulation. Furthermore, we validate our previous finding that complex 1 of the electron transport chain (ETC) is destabilized in hyperoxia, explaining the exacerbation of associated disease models by hyperoxia and rescue by hypoxia. Moreover, we nominate MYBBP1A as a novel transcriptional regulator in hyperoxic lung, particularly in the context of rRNA homeostasis. Overall, our study highlights the importance of the effects of oxygen tensions on protein turnover rates and identifies novel tissue-specific mediators of oxygen-dependent responses.

2023-12-10 | GSE234123 | GEO

In Vivo Protein Turnover Rates in Varying Oxygen Tensions Nominate MYBBP1A as a Novel Mediator of the Hyperoxia Response

Project description:Oxygen deprivation and excess are both toxic to mammals. Thus, the ability to adapt to varying oxygen tensions is critical for survival. While the transcriptional response to acute hypoxia has been well-studied, the post-translational effects of hypoxia and hyperoxia have been underexplored. In this study, we systematically investigate protein turnover rates in mouse heart, lung, and brain under different inhaled oxygen tensions. We find that the lung proteome is the most responsive to changes in oxygen tension, likely due to the direct exposure of alveoli to inhaled oxygen. In particular, several extracellular matrix (ECM) proteins such as collagens and laminins, are stabilized in the lung under both hypoxia and hyperoxia, suggesting their post-translational regulation. Furthermore, we validate our previous finding that complex 1 of the electron transport chain (ETC) is destabilized in hyperoxia, explaining the exacerbation of associated disease models by hyperoxia and rescue by hypoxia. Moreover, we nominate MYBBP1A as a novel transcriptional regulator in hyperoxic lung, particularly in the context of rRNA homeostasis. Overall, our study highlights the importance of the effects of oxygen tensions on protein turnover rates and identifies novel tissue-specific mediators of oxygen-dependent responses.

2023-06-04 | MSV000092095 | MassIVE

Murine LSK proteome Raw data 20240512

Project description:murine hematopoietic stem progenitor cells proteome Raw data

2024-05-16 | PXD052330 |

Ageing-associated proteome and acetylome of hematopoietic progenitor cells

Project description:Ageing-associated proteome and acetylome of hematopoietic progenitor cells

2020-09-24 | PXD021651 |

Controlling pericellular oxygen tension in cell culture reveals distinct breast cancer responses to low oxygen tensions

Project description:Controlling pericellular oxygen tension in cell culture reveals distinct breast cancer responses to low oxygen tensions

| PRJNA1129053 | ENA

Competition between hematopoietic stem and progenitor cells controls the hematopoietic stem cell homeostasis [scRNA-seq]

Project description:Cellular competition for limiting hematopoietic factors is a physiologically regulated but poorly understood process. Here, we studied this phenomenon by hampering hematopoietic progenitor access to Leptin receptor+ mesenchymal stem/progenitor cells (MSPCs) and endothelial cells (ECs). We showed that HSC numbers increased by 2-fold when multipotent and lineage-restricted progenitors fail to respond to CXCL12 produced by MSPCs and ECs. HSCs were qualitatively normal, and HSC expansion only occurred when early hematopoietic progenitors but not differentiated hematopoietic cells lacked CXCR4. Furthermore, the MSPC and EC transcriptomic heterogeneity was remarkably stable, suggesting that it is impervious to dramatic changes in hematopoietic progenitor interactions. Instead, HSC expansion was caused by increased availability of membrane-bound stem cell factor (mSCF) on MSPCs and ECs due to reduced consumption by cKit-expressing hematopoietic progenitors. These studies revealed an intricate homeostatic balance between HSCs and proximal hematopoietic progenitors regulated by cell competition for limiting amounts of mSCF.

2021-03-29 | GSE171014 | GEO

Competition between hematopoietic stem and progenitor cells controls the hematopoietic stem cell homeostasis [bulk RNA-seq]

2021-03-29 | GSE171013 | GEO

FOS Guards Quiescence and Potency in Human Hematopoietic Stem Cells [scRNA-seq]

Project description:Quiescence and limited dividing are critical in preserving potency of hematopoietic stem/progenitor cell (HSPCs) during lifetime, but little is known about how this process is regulated. Here, we show that the mobilized human HSPCs in peripheral blood (PB) are predominantly in a quiescent state, but rapidly exit quiescence and reduce repopulating potency in short-term culture. Through single cell RNA-seq, we identified a panel of regulators highly associated with HSC quiescence exit and cell-cycle entry. These regulators involve different biological processes such as cell-cycle, signaling pathways, metabolisms, etc. Among them, the oncogene, FOS restrains cell-cycle entry and supports repopulating potency in human HSCs through directly binding and regulating genes both for HSC quiescence and potency. Our findings uncover the regulatory program underlying quiescence exit and highlight the critical role of FOS to guard the quiescence and potency in human HSPCs.

2021-06-08 | GSE176272 | GEO

FOS Guards Quiescence and Potency in Human Hematopoietic Stem Cells [RNA-seq]

2021-06-08 | GSE176317 | GEO