Adenosine signaling promotes hematopoietic stem and progenitor cell emergence

Jing, Lili; Tamplin, Owen J.; Chen, Michael; Deng, Qing; Patterson, Shenia; Kim, Peter Geon; Durand, Ellen M.; McNeil, Ashley; Green, Julie M.; Matsuura, Shinobu; Ablain, Julien; Brandt, Margot; Schlaeger, Thorsten M.; Huttenlocher, Anna; Daley, George Q.; Ravid, Katya; Zon, Leonard I.

doi:10.1083/jcb.2092oia68

Cited by 20 publications

(23 citation statements)

References 27 publications

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“…Besides its direct function as adhesion molecule, this membrane-bound enzyme catalyzes the extracellular conversion of adenosine monophosphate to adenosine. This pathway is particularly interesting in light of recent evidence for a functional role of adenosine signaling in HSC emergence in zebrafish (Jing et al, 2015). Moreover, adenosine receptor signaling was suggested to enhance cycling of hematopoietic progenitor cells (Pospísil et al, 2001), in line with the proposed impact of the sinusoids on HSC proliferation.…”

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confidence: 80%

In Vivo Labeling by CD73 Marks Multipotent Stromal Cells and Highlights Endothelial Heterogeneity in the Bone Marrow Niche

et al. 2018

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Despite much work studying ex vivo multipotent stromal cells (MSCs), the identity and characteristics of MSCs in vivo are not well defined. Here, we generated a CD73-EGFP reporter mouse to address these questions and found EGFP MSCs in various organs. In vivo, EGFP mesenchymal cells were observed in fetal and adult bones at proliferative ossification sites, while in solid organs EGFP cells exhibited a perivascular distribution pattern. EGFP cells from the bone compartment could be clonally expanded ex vivo from single cells and displayed trilineage differentiation potential. Moreover, in the central bone marrow CD73-EGFP specifically labeled sinusoidal endothelial cells, thought to be a critical component of the hematopoietic stem cell niche. Purification and molecular characterization of this CD73-EGFP population revealed an endothelial subtype that also displays a mesenchymal signature, highlighting endothelial cell heterogeneity in the marrow. Thus, the CD73-EGFP mouse is a powerful tool for studying MSCs and sinusoidal endothelium.

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confidence: 80%

In Vivo Labeling by CD73 Marks Multipotent Stromal Cells and Highlights Endothelial Heterogeneity in the Bone Marrow Niche

et al. 2018

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“…Moreover, since the Nlrp3 inflammasome is strongly activated by the extracellular purine nucleotide eATP, these effects on the HSPC response depend on purinergic signaling in which eATP is the principal stimulatory mediator [44,[55][56][57]. The role of purinergic signaling in hematopoietic development has been convincingly demonstrated by another group in a zebra fish model in the context of the prohematopoietic effects of the eATP metabolite extracellular adenosine (eAdo) [58].…”

Section: Does Nlrp3 Inflammasome Signaling Contribute To the Developmmentioning

confidence: 98%

The Nlrp3 inflammasome as a “rising star” in studies of normal and malignant hematopoiesis

et al. 2020

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Recent investigations indicate that hematopoiesis is coregulated by innate immunity signals and by pathways characteristic of the activation of innate immunity cells that also operate in normal hematopoietic stem progenitor cells (HSPCs). This should not be surprising because of the common developmental origin of these cells from a hemato/lymphopoietic stem cell. An important integrating factor is the Nlrp3 inflammasome, which has emerged as a major sensor of changes in body microenvironments, cell activation, and cell metabolic activity. It is currently the best-studied member of the inflammasome family expressed in hematopoietic and lymphopoietic cells, including also HSPCs. It is proposed as playing a role in (i) the development and expansion of HSPCs, (ii) their release from bone marrow (BM) into peripheral blood (PB) in stress situations and during pharmacological mobilization, (iii) their homing to BM after transplantation, and (iv) their aging and the regulation of hematopoietic cell metabolism. The Nlrp3 inflammasome is also involved in certain hematological pathologies, including (i) myelodysplastic syndrome, (ii) myeloproliferative neoplasms, (iii) leukemia, and (iv) graft-versus-host disease (GvHD) after transplantation. The aim of this review is to shed more light on this intriguing intracellular protein complex that has become a "rising star" in studies focused on both normal steady-state and pathological hematopoiesis.

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“…Laboratory investigations have led to several important observations that helped clarify the molecular mechanisms underlying HSC development and activation. For example, adenosine signaling plays an evolutionary conserved role in HSC formation in vertebrates . Tzeng and colleagues demonstrated that the stroma‐secreted CXCL12 (stromal cell‐derived factor‐1) keeps the HSCs in a quiescent state and maintains them in the osteoblastic niche .…”

Section: Introductionmentioning

confidence: 99%

Dipeptidyl Peptidase‐4 Regulates Hematopoietic Stem Cell Activation in Response to Chronic Stress

Zhu

Hu²,

et al. 2017

JAHA

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BackgroundDPP4 (Dipeptidyl peptidase‐4)‐GLP‐1 (glucagon‐like peptide‐1) and its receptor (GLP‐1R) axis has been involved in several intracellular signaling pathways. The Adrβ3 (β3‐adrenergic receptor)/CXCL12 (C‐X‐C motif chemokine 12) signal was required for the hematopoiesis. We investigated the novel molecular requirements between DPP4‐GLP‐1/GLP‐1 and Adrβ3/CXCL12 signals in bone marrow (BM) hematopoietic stem cell (HSC) activation in response to chronic stress.Methods and ResultsMale 8‐week‐old mice were subjected to 4‐week intermittent restrain stress and orally treated with vehicle or the DPP4 inhibitor anagliptin (30 mg/kg per day). Control mice were left undisturbed. The stress increased the blood and brain DPP4 levels, the plasma epinephrine and norepinephrine levels, and the BM niche cell Adrβ3 expression, and it decreased the plasma GLP‐1 levels and the brain GLP‐1R and BM CXCL12 expressions. These changes were reversed by DPP4 inhibition. The stress activated BM sca‐1highc‐Kithigh CD48low CD150high HSC proliferation, giving rise to high levels of blood leukocytes and monocytes. The stress‐activated HSC proliferation was reversed by DPP4 depletion and by GLP‐1R activation. Finally, the selective pharmacological blocking of Adrβ3 mitigated HSC activation, accompanied by an improvement of CXCL12 gene expression in BM niche cells in response to chronic stress.ConclusionsThese findings suggest that DPP4 can regulate chronic stress‐induced BM HSC activation and inflammatory cell production via an Adrβ3/CXCL12‐dependent mechanism that is mediated by the GLP‐1/GLP‐1R axis, suggesting that the DPP4 inhibition or the GLP‐1R stimulation may have applications for treating inflammatory diseases.

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Adenosine signaling promotes hematopoietic stem and progenitor cell emergence

Cited by 20 publications

References 27 publications

In Vivo Labeling by CD73 Marks Multipotent Stromal Cells and Highlights Endothelial Heterogeneity in the Bone Marrow Niche

In Vivo Labeling by CD73 Marks Multipotent Stromal Cells and Highlights Endothelial Heterogeneity in the Bone Marrow Niche

The Nlrp3 inflammasome as a “rising star” in studies of normal and malignant hematopoiesis

Dipeptidyl Peptidase‐4 Regulates Hematopoietic Stem Cell Activation in Response to Chronic Stress

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