Kinetic‐microarchitectural Correlations in the Bone Marrow of the Mouse

Shackney, Stanley E.; Ford, Sharon S.; Wittig, A.

doi:10.1111/j.1365-2184.1975.tb01237.x

Cited by 34 publications

(22 citation statements)

References 14 publications

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“…Of course, migration into and/or away from different microenvironments is a well-known paradigm of differentiation in the embryo. In addition, progenitor migration between different extracellular microenvironments is an integral component of steady state differentiation in a variety of postnatal tissues, including the epidermis (40), intestinal crypts (41), germ cells (42,43), and even bone marrow (44,45). Frequently, the divergence of independent cell fates, i.e., commitment to one lineage vs another, or self-renewal vs differentiation, is intricately linked to the position of a given stem/progenitor cell relative to other cells in its microenvironment.…”

Section: Discussionmentioning

confidence: 99%

Stromal Cells Provide the Matrix for Migration of Early Lymphoid Progenitors Through the Thymic Cortex

Prockop

Palencia

Ryan

et al. 2002

The Journal of Immunology

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During steady state lymphopoiesis in the postnatal thymus, migration of precursors outward from the deep cortex toward the capsule is required for normal differentiation. Such migration requires, at a minimum, expression of adhesive receptors on the migrating lymphoid cells, as well as a stable matrix of their ligands persisting throughout the region of migration. In this study, we address the nature of this adhesive matrix. Although some precursor stages bound efficiently to extracellular matrix ligands, a specific requirement for the cell surface ligand VCAM-1 was also found. In situ analysis revealed that early precursors are found in intimate contact with a matrix formed by stromal cells in the cortex, a proportion of which expresses VCAM-1. In vivo administration of an anti-VCAM-1 Ab resulted in decreased thymic size and altered distribution of early precursors within the cortex. These results indicate that precursors migrating outward through the cortex may use a cellular, rather than extracellular, matrix for adhesion, and suggest that the VCAM-1+ subset of cortical stroma may play a crucial role in supporting the migration of early precursors in the steady state thymus.

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Section: Discussionmentioning

confidence: 99%

Stromal Cells Provide the Matrix for Migration of Early Lymphoid Progenitors Through the Thymic Cortex

Prockop

Palencia

Ryan

et al. 2002

The Journal of Immunology

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“…1,2 MKPs are thought to reside near the bone surface in an "endosteal niche," where environmental cues encourage expansion, but suppress terminal maturation. [3][4][5][6] Polyploid MKs mature cytoplasmically, extrude proplatelets in association with sinusoidal vasculature, and shed platelets into the peripheral blood. [7][8][9] This process results in past-maturity "exhausted" MKs comprised of a nucleus with a thin layer of cytoplasm surrounded by a cell membrane.…”

Section: Introductionmentioning

confidence: 99%

SDF-1 dynamically mediates megakaryocyte niche occupancy and thrombopoiesis at steady state and following radiation injury

Niswander

Fegan²,

Kingsley³

et al. 2014

Blood

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• SDF-1 acutely affects megakaryocyte spatial distribution in the bone marrow at steady state and in the setting of radiation injury.• SDF-1-directed localization of megakaryocytes into the vascular niche increases platelet output.Megakaryocyte (MK) development in the bone marrow progresses spatially from the endosteal niche, which promotes MK progenitor proliferation, to the sinusoidal vascular niche, the site of terminal maturation and thrombopoiesis. The chemokine stromal cellderived factor-1 (SDF-1), signaling through CXCR4, is implicated in the maturational chemotaxis of MKs toward sinusoidal vessels. Here, we demonstrate that both IV administration of SDF-1 and stabilization of endogenous SDF-1 acutely increase MKvasculature association and thrombopoiesis with no change in MK number. In the setting of radiation injury, we find dynamic fluctuations in marrow SDF-1 distribution that spatially and temporally correlate with variations in MK niche occupancy. Stabilization of altered SDF-1 gradients directly affects MK location. Importantly, these SDF-1-mediated changes have functional consequences for platelet production, as the movement of MKs away from the vasculature decreases circulating platelets, while MK association with the vasculature increases circulating platelets. Finally, we demonstrate that manipulation of SDF-1 gradients can improve radiation-induced thrombocytopenia in a manner additive with earlier TPO treatment. Taken together, our data support the concept that SDF-1 regulates the spatial distribution of MKs in the marrow and consequently circulating platelet numbers. This knowledge of the microenvironmental regulation of the MK lineage could lead to improved therapeutic strategies for thrombocytopenia. (Blood. 2014;124(2):277-286) Introduction Platelet-producing megakaryocytes (MKs) are derived from megakaryocyte progenitors (MKPs), which are defined functionally by their capacity to form colonies in vitro. 1,2 MKPs are thought to reside near the bone surface in an "endosteal niche," where environmental cues encourage expansion, but suppress terminal maturation.3-6 Polyploid MKs mature cytoplasmically, extrude proplatelets in association with sinusoidal vasculature, and shed platelets into the peripheral blood. [7][8][9] This process results in past-maturity "exhausted" MKs comprised of a nucleus with a thin layer of cytoplasm surrounded by a cell membrane. 10,11 Megakaryopoiesis is primarily regulated by the cytokine thrombopoietin (TPO), which signals through its receptor Mpl to promote MKP proliferation and MK maturation. [12][13][14] Although the physical association of MKs with sinusoidal vasculature was first appreciated several decades ago, 15-17 the functional significance of the "vascular niche" for MK maturation and thrombopoiesis has only more recently begun to be elucidated. 4,[18][19][20][21] Several studies have implicated the chemokine stromal cellderived factor-1 ([SDF-1] or CXCL12) signaling through receptor CXCR4 in the maturational localization of MKs to the vascular nic...

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“…These results well supported the findings previously obtained in vivo that: (1) in murine BM, hematopoietic progenitors are distributed along the oxygen gradient, MRA progenitors being more concentrated where oxygen tension is Correspondence: P Dello Sbarba, Dipartimento di Patologia e Oncologia Sperimentali, viale GB Morgagni 50 -50134 Firenze, Italy; Fax: 390 5541 6908 Received 17 August 1999; accepted 16 December 1999 lower while CFU-GM reside preferentially in the best-oxygenated subendosteal areas, and (2) the probability of progenitors to be recruited into the mitotic cycle is inversely related to their distance from those areas. [6][7][8] In the experiments reported in this paper, liquid cultures of murine BM cells (BMC) supplemented with granulocyte/ macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL3) were used to: (1) determine whether the inhibition of hematopoiesis in hypoxia is reversible; (2) characterize the hypoxia-maintained progenitors on the basis of their in vitro expansion potential, as measured by transferring hypoxic cultures to air; (3) compare these progenitors with progenitors detectable by the MRA assays. The results indicated that the hypoxia-dependent block of the expansion of hematopoietic clones is reversible.…”

Section: Introductionmentioning

confidence: 99%

The expansion of murine bone marrow cells preincubated in hypoxia as an in vitro indicator of their marrow-repopulating ability

et al. 2000

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In liquid cultures of murine bone marrow cells stimulated with interleukin-3 and granulocyte/macrophage colony-stimulating factor, hypoxia (1% oxygen) induced a reversible block of hematopoiesis, maintaining the progenitors' expansion potential unreduced. Progenitors repopulating day-14 hypoxic cultures with cells or granulocyte/macrophage colony-forming units (CFU-GM) were found, on the basis of their maintenance in hypoxia (12% and 76%, respectively), to belong to different subsets, the latter being much more efficiently maintained. The maintenance in hypoxic cultures of progenitors detectable by marrow-repopulating ability (MRA) assay was 18% for MRA cell progenitors and 69% for MRA CFU progenitors. Thus, the repopulation of hypoxic cultures with cells or CFU-GM closely reflected the presence of progenitors capable of repopulating, with cells or CFU-GM, the bone marrow of lethally irradiated syngeneic animals. Progenitors repopulating hypoxic cultures were, like MRA progenitors, significantly resistant to 5-fluorouracil, progenitors repopulating cultures with CFU-GM being two-fold more resistant than those repopulating cultures with cells. We concluded that the repopulation of day-14 hypoxic cultures occurring after their transfer to air is to be considered an indicator of the maintenance of MRA progenitors in hypoxia. The relevance of these results to stem cell biology and their potential practical applications are discussed. Leukemia (2000) 14, 735-739.

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Kinetic‐microarchitectural Correlations in the Bone Marrow of the Mouse

Cited by 34 publications

References 14 publications

Stromal Cells Provide the Matrix for Migration of Early Lymphoid Progenitors Through the Thymic Cortex

Stromal Cells Provide the Matrix for Migration of Early Lymphoid Progenitors Through the Thymic Cortex

SDF-1 dynamically mediates megakaryocyte niche occupancy and thrombopoiesis at steady state and following radiation injury

The expansion of murine bone marrow cells preincubated in hypoxia as an in vitro indicator of their marrow-repopulating ability

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