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Neogenin-1 distinguishes between myeloid-biased and balanced Hoxb5+ mouse long-term hematopoietic stem cells

ABSTRACT: Neogenin-1 distinguishes between myeloid-biased and balanced Hoxb5+ mouse long-term hematopoietic stem cells

PROVIDER: PRJNA540492 | ENA |

REPOSITORIES: ENA

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Neogenin-1 distinguishes between myeloid-biased and balanced Hoxb5+ mouse long-term hematopoietic stem cells

Project description:Hematopoietic stem cells (HSCs) self-renew and generate all blood cells. Recent studies with single-cell transplants and lineage tracing suggest that adult HSCs are diverse in their reconstitution and lineage potentials. However, prospective isolation of these subpopulations has remained challenging. Here, we identify Neogenin-1 (NEO1) as a unique surface marker on a fraction of mouse HSCs labeled with Hoxb5, a specific reporter of long-term HSCs (LT-HSCs). We show that NEO1+Hoxb5+ LT-HSCs expand with age and respond to myeloablative stress in young mice, while NEO1–Hoxb5+ LT-HSCs exhibit no significant change in number. Furthermore, NEO1+Hoxb5+ LT-HSCs are more often in the G2/S cell cycle phase compared to NEO1–Hoxb5+ LT-HSCs in both young and old bone marrow. Upon serial transplantation, NEO1+Hoxb5+ LT-HSCs exhibit myeloid-biased differentiation and reduced reconstitution, while NEO1–Hoxb5+ LT-HSCs are lineage-balanced and stably reconstitute recipients. Gene expression analysis reveals erythroid and myeloid priming in the NEO1+ fraction and association of quiescence and self-renewal-related transcription factors with NEO1− LT-HSCs. Finally, transplanted NEO1+Hoxb5+ LT-HSCs rarely generate NEO1–Hoxb5+ LT-HSCs, while NEO1–Hoxb5+ LT-HSCs repopulate both LT-HSC fractions. This supports a model in which dormant, balanced, NEO1–Hoxb5+ LT-HSCs can hierarchically precede active, myeloid-biased NEO1+Hoxb5+ LT-HSCs.

2019-11-10 | GSE130504 | GEO

Neogenin-1 distinguishes between myeloid-biased and balanced Hoxb5 + mouse long-term hematopoietic stem cells.

Project description: Not available

| S-EPMC6911217 | biostudies-literature

Hoxb5 reprograms murine multipotent blood progenitors into hematopoietic stem cell-like cells

Project description:We performed the single cell RNA-seq for the Hoxb5 Mac-1+CD48+ SK cells, bone marrow HSC, bone marrow MPP, and fetal liver HSC by Smart-Seq2.

2022-06-30 | GSE183800 | GEO

Transcription factor Hoxb5 reprograms B cells into functional T lymphocytes [ChIP-Seq]

Project description:Chipseq were performed to analyze the targets of Hoxb5 in pro-/pre-B by over expression.

2018-02-07 | GSE105007 | GEO

Transcription factor Hoxb5 reprograms B cells into functional T lymphocytes [RNA-seq2]

Project description:Here we were performed RNAseq to analyze the transcriptome changing of Hoxb5 in Pro/pre-B by over expression.

2018-02-07 | GSE105768 | GEO

Differential gene expression profiles between myeloid-biased and lymphoid-biased hematopoietic stem cells.

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

Hoxb5 reprograms murine multipotent blood progenitors into hematopoietic stem cell-like cells

Project description:Hoxb5 reprograms murine multipotent blood progenitors into hematopoietic stem cell-like cells

| PRJNA762032 | ENA

Mapping AT1R biased signaling using proximity-labeling and proteomics identifies diverse actions of biased agonists

Project description:Angiotensin II type 1 receptors (AT1Rs) are one of the most widely studied G protein-coupled receptors. To fully appreciate the diversity in cellular signaling profiles activated by AT1R transducer-biased ligands, we utilized peroxidase-catalyzed proximity labeling to capture proteins in close proximity to AT1Rs in response to six different ligands: Angiotensin II (full agonist), S1I8 (partial agonist), TRV055 and TRV056 (G protein-biased agonists), TRV026 and TRV027 (β-arrestin biased agonists) at 90s, 10min, and 60min after stimulation. We systematically analyzed the kinetics of AT1R trafficking and determined that distinct ligands lead AT1R to different cellular compartments for downstream signaling activation and receptor degradation/recycling. Distinct proximity labelling of proteins from a number of functional classes, including GTPases, adaptor proteins, and kinases were activated by different ligands suggesting unique signaling and physiological roles of the AT1R. Ligands within the same class, i.e. either G protein-biased or -arrestin-biased, shared high similarity in their labelling profiles. Comparison between ligand classes revealed distinct signaling activation such as greater labeling by G protein biased ligands on ESCRT-0 complex proteins that act as sorting machinery for ubiquitinated proteins. Our study provides a comprehensive analysis of AT1R receptor trafficking kinetics and signaling activation profiles induced by distinct classes of ligands.

2021-03-25 | PXD023814 | Pride

MicroRNA-125b expands hematopoietic stem cells and enriches for the lymphoid-balanced and lymphoid-biased subsets.

Project description: Not available

| S-EPMC3003003 | biostudies-literature

Sox6 expression distinguishes dorsally and ventrally biased dopamine neurons in the substantia nigra with distinctive properties and embryonic origins

Project description:Sox6 expression distinguishes dorsally and ventrally biased dopamine neurons in the substantia nigra with distinctive properties and embryonic origins

| PRJNA769144 | ENA

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