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Distinct Bone Marrow Sources of Pleiotrophin Control Hematopoietic Stem Cell Maintenance and Regeneration.

Cell stem cell | 2018

Bone marrow (BM) perivascular stromal cells and vascular endothelial cells (ECs) are essential for hematopoietic stem cell (HSC) maintenance, but the roles of distinct niche compartments during HSC regeneration are less understood. Here we show that Leptin receptor-expressing (LepR+) BM stromal cells and ECs dichotomously regulate HSC maintenance and regeneration via secretion of pleiotrophin (PTN). BM stromal cells are the key source of PTN during steady-state hematopoiesis because its deletion from stromal cells, but not hematopoietic cells, osteoblasts, or ECs, depletes the HSC pool. Following myelosuppressive irradiation, PTN expression is increased in bone marrow endothelial cells (BMECs), and PTN ECs are more frequent in the niche. Moreover, deleting Ptn from ECs impairs HSC regeneration whereas Ptn deletion from BM stromal cells does not. These findings reveal dichotomous and complementary regulation of HSC maintenance and regeneration by BM stromal cells and ECs.

Pubmed ID: 30100167 RIS Download

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Antibodies used in this publication

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Alexa Fluor® 488 anti-mouse CD41 antibody (antibody)

RRID:AB_10645332

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Lineage Antibody Cocktail, with Isotype Control (antibody)

RRID:AB_10611731

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Rat IgG2b, k antibody (antibody)

RRID:AB_1645681

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Rat IgG2b, k antibody (antibody)

RRID:AB_10063104

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Rat IgG2a Clone: R35-95, R-Phycoerythrin Conjugated/Tagged antibody (antibody)

RRID:AB_479719

This unknown targets Rat IgG2a Clone: R35-95 R-Phycoerythrin /Tagged

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CD34 antibody (antibody)

RRID:AB_395017

This monoclonal antibody targets CD34

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NG2 antibody [132.38] (antibody)

RRID:AB_881569

This monoclonal antibody targets NG2 antibody [132.38]

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Mouse Osteopontin (OPN) Affinity Purified Polyclonal Ab antibody (antibody)

RRID:AB_2194992

This polyclonal antibody targets Mouse Osteopontin (OPN) Affinity Purified Ab

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Rabbit Anti-Leptin receptor(L/M/S) Polyclonal Antibody, FITC Conjugated (antibody)

RRID:AB_11074292

This polyclonal antibody targets Rabbit Leptin receptor(L/M/S) FITC

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Rat IgG2a, k antibody (antibody)

RRID:AB_396799

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Perilipin Antibody (antibody)

RRID:AB_715043

This polyclonal antibody targets Perilipin

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CD3 Molecular Complex antibody (antibody)

RRID:AB_10679120

This monoclonal antibody targets CD3 Molecular Complex

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Rabbit Anti-Endomucin Polyclonal Antibody, Unconjugated (antibody)

RRID:AB_11090525

This polyclonal antibody targets Rabbit Endomucin

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Human/Mouse CXCL12/SDF-1 Allophycocyanin MAb (Clone 79018) antibody (antibody)

RRID:AB_1964550

This monoclonal antibody targets Human/Mouse CXCL12/SDF-1 Allophycocyanin MAb (Clone 79018)

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Ly-6G and Ly-6C antibody (antibody)

RRID:AB_394644

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CD45R/B220 antibody (antibody)

RRID:AB_394335

This monoclonal antibody targets CD45R/B220

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Rat IgG2a, kappa Isotype Control, APC-Cy7 Conjugated, Clone R35-95 antibody (antibody)

RRID:AB_394456

This unknown targets Rat IgG2a kappa Isotype Control APC-Cy7 Clone R35-95

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Mouse/Rat CD31/PECAM-1 Alexa Fluor 488 Affinity Purified PAb antibody (antibody)

RRID:AB_10972784

This polyclonal antibody targets Mouse/Rat CD31/PECAM-1 Alexa Fluor 488 Affinity Purified PAb

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Rat IgG1, kappa Isotype Control, FITC Conjugated, Clone R3-34 antibody (antibody)

RRID:AB_395508

This unknown targets Rat IgG1 kappa Isotype Control FITC Clone R3-34

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CD45 antibody (antibody)

RRID:AB_1645275

This monoclonal antibody targets CD45

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Goat anti-Chicken IgY (H+L) Cross-Adsorbed Secondary Antibody, DyLight 488 (antibody)

RRID:AB_2556650

This polyclonal antibody targets Chicken IgY (H+L) Cross-Adsorbed

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CD135 antibody (antibody)

RRID:AB_1727425

This monoclonal antibody targets CD135

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Rat IgG2a Clone: R35-95, FITC Conjugated/Tagged antibody (antibody)

RRID:AB_479727

This unknown targets Rat IgG2a Clone: R35-95 FITC /Tagged

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Rat IgG2b, k antibody (antibody)

RRID:AB_10049479

This monoclonal antibody targets Rat IgG2b k

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GraphPad Prism (tool)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

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ImageJ (tool)

RRID:SCR_003070

Software tool as an open source Java-based image processing program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.

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Fiji (tool)

RRID:SCR_002285

Software package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.

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FlowJo (tool)

RRID:SCR_008520

Software for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.

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