Endothelial Jak3 expression enhances pro-hematopoietic angiocrine function
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA670425 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12858320_1.fastq.gz | Fastqsanger.gz | |||
| SRR12858320_2.fastq.gz | Fastqsanger.gz | |||
| SRR12858321_1.fastq.gz | Fastqsanger.gz | |||
| SRR12858321_2.fastq.gz | Fastqsanger.gz | |||
| SRR12858322_1.fastq.gz | Fastqsanger.gz |
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Project description:Jak3 is the only non-promiscuous member of the Jak family of secondary messengers. Jak3–/– mice display defective T and NK cell development, which results in a SCID phenotype. As a result, studies to date have focused on understanding and targeting the cell-autonomous role of Jak3 in immunity, while functional Jak3 expression outside the hematopoietic system remains largely unreported. We show that Jak3 is expressed in endothelial cells across hematopoietic and non-hematopoietic organs, with heightened expression in the bone marrow. The bone marrow niche is understood as a network of different cell types that regulate hematopoietic function. We show that the Jak3–/– bone marrow niche is deleterious for the maintenance of long-term repopulating hematopoietic stem cells (LT-HSCs) and that JAK3-overexpressing endothelial cells have increased potential to expand LT-HSCs in vitro. Increased arterial zonation in the bone marrow of Jak3–/– mice further situates Jak3 as a marker of sinusoidal endothelium. This work may serve to identify a novel function for a highly specific tyrosine kinase in the bone marrow vascular niche and to further characterize the LT-HSC function of sinusoidal endothelium.
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Project description:Jak3 is the only non-promiscuous member of the Jak family of secondary messengers. Studies to date have focused on understanding and targeting the cell-autonomous role of Jak3 in immunity, while functional Jak3 expression outside the hematopoietic system remains largely unreported. We show that Jak3 is expressed in endothelial cells across hematopoietic and non-hematopoietic organs, with heightened expression in the bone marrow. The bone marrow niche is understood as a network of different cell types that regulate hematopoietic function. We show that the Jak3-/- bone marrow niche is deleterious for the maintenance of long-term repopulating hematopoietic stem cells (LT-HSCs) and that JAK3-overexpressing endothelial cells have increased potential to expand LT-HSCs in vitro. This work may serve to identify a novel function for a highly specific tyrosine kinase in the bone marrow vascular niche and to further characterize the LT-HSC function of sinusoidal endothelium.
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