Bone marrow dendritic cells regulate hematopoietic stem/progenitor cell trafficking

Zhang, Jingzhu; Supakorndej, Teerawit; Krambs, Joseph R.; Rao, Mahil; Abou-Ezzi, Grazia; Ye, Rachel Y.; Li, Sidan; Trinkaus, Kathryn; Link, Daniel C.

doi:10.1172/jci124829

Cited by 45 publications

(30 citation statements)

References 51 publications

(63 reference statements)

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“…2e, f and Supplementary Video 6). In agreement with previous studies 28, 29 we found that cDC form clusters ( Fig. 2a and Extended Data Fig.…”

Section: Atlases Of Steady State Myelopoiesissupporting

confidence: 94%

Three-dimensional mapping identifies distinct vascular niches for myelopoiesis

Zhang

Johnson

et al. 2020

Preprint

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In contrast to virtually all other tissues in the body the anatomy of differentiation in the bone marrow remains unknown. This is due to the lack of strategies to examine blood cell production in situ, which are required to better understand differentiation, lineage commitment decisions, and to define how spatial organizing cues inform tissue function. Here we developed imaging approaches to map all myeloid cells in whole bones and generated 3D atlases of granulocyte and monocyte/dendritic cell differentiation during homeostasis. We found that myeloid progenitors leave the hematopoietic stem cell niche during differentiation.Granulocyte and monocyte dendritic cell progenitors (MDP) do not interact, instead they localize to different sinusoids where they give rise to clusters of immature cells. MDP cluster with Ly6C lo monocytes and conventional dendritic cells; these localize to a unique subset of colony stimulating factor 1 (CSF1, the major regulator of monopoiesis 1 ) -expressing sinusoids. Csf1 deletion in the vasculature disrupted the MDP clusters and their interaction with sinusoids, leading to reduced MDP numbers and differentiation ability, with subsequent loss of peripheral Ly6C lo monocytes and dendritic cells. These data indicate that there is a specific spatial organization of definitive hematopoiesis and that local cues produced by distinct blood vessels are responsible for this organization. These maps provide a blueprint for in situ analyses of hematopoiesis in blood disorders.

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“…2e, f and Supplementary Video 6). In agreement with previous studies 28, 29 we found that cDC form clusters ( Fig. 2a and Extended Data Fig.…”

Section: Atlases Of Steady State Myelopoiesissupporting

confidence: 94%

Three-dimensional mapping identifies distinct vascular niches for myelopoiesis

Zhang

Johnson

et al. 2020

Preprint

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“…Egress of stem cells from BM is orchestrated by activation of purinergic signaling that involves release of adenosine triphosphate (ATP) from activated BM cells belonging to innate immunity - including granulocytes, monocytes, and as recently demonstrated also dendritic cells [2, 3]. Extracellular ATP triggers, after binding to purinergic P2X7 receptor, a sequence of events leading to the activation of Nlrp3 inflammasome [11, 21–25] that activates in the BM microenvironment complement cascade (ComC) in which cleavage products C5a, desrArg C5a, and C5bC9 are required for optimal egress of HSPCs from BM into PB [2, 8–12].…”

Section: Discussionmentioning

confidence: 99%

The Inhibition of CD39 and CD73 Cell Surface Ectonucleotidases by Small Molecular Inhibitors Enhances the Mobilization of Bone Marrow Residing Stem Cells by Decreasing the Extracellular Level of Adenosine

Adamiak

Bujko

Brzeźniakiewicz‐Janus

et al. 2019

Stem Cell Rev and Rep

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We have recently demonstrated that purinergic signaling in bone marrow (BM) microenvironment regulates mobilization of hematopoietic stem progenitor cells (HSPCs), mesenchymal stroma cells (MSCs), endothelial progenitor cells (EPCs), and very small embryonic like stem cells (VSELs) into the peripheral blood (PB). While extracellular adenosine triphosphate (ATP) promotes mobilization, its metabolite extracellular adenosine has an opposite effect. Since ATP is processed in extracellular space to adenosine by ectonucleotidases including cell surface expressed CD39 and CD73, we asked if inhibition of these enzymes by employing in vivo small molecular inhibitors ARL67156 and AMPCP of CD39 and CD73 respectively, alone or combined could enhance granulocyte stimulating factor (G-CSF)- and AMD3100-induced pharmacological mobilization of stem cells. Herein we report that pre-treatment of donor mice with CD39 and CD73 inhibitors facilitates the mobilization of HSPCs as well as other types of BM-residing stem cells. This data on one hand supports the role of purinergic signaling in stem cell trafficking, and on the other since both compounds are not toxic against human cells, they could be potentially employed in the clinic to enhance the mobilization of BM residing stem cells for clinical purposes.Electronic supplementary materialThe online version of this article (10.1007/s12015-019-09918-y) contains supplementary material, which is available to authorized users.

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“…Finally dendritic cells are spread inside all four BM compartments, in perivascular locations including arterioles and venous sinuses, and in close contact to both endothelial and adventitial reticular cells (28).…”

Section: T and B Lymphocytes And Dendritic Cellsmentioning

confidence: 99%

“…Dendritic cells are professional antigen-presenting cells that in the BM are better known as type 2 conventional dendritic cells (cDC2). They regulate memory of local T cells, promote survival of recirculating mature B cells, and by interacting with endothelial and adventitial reticular cells mobilize HSC, uncommitted progenitors, and OMCs in the hemopoietic niche (28). From the point of view of a local information system, they look like a multiplexer able to select numerous inputs toward a single output (either a prevalent immune or osteoregulatory response).…”

Section: Dendritic Cellsmentioning

confidence: 99%