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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

Additional research tools detected in this publication

None found

Antibodies used in this publication

Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: U01 AI138331
  • Agency: NIAID NIH HHS, United States
    Id: U01 AI107333
  • Agency: NIAID NIH HHS, United States
    Id: U19 AI067769
  • Agency: NHLBI NIH HHS, United States
    Id: K08 HL138305
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL086998

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Perilipin Antibody (antibody)

RRID:AB_715043

This polyclonal targets Perilipin

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NG2 antibody [132.38] (antibody)

RRID:AB_881569

This monoclonal targets Rat NG2

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

RRID:AB_10972784

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

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

RRID:AB_2194992

This polyclonal targets Mouse Osteopontin (OPN) Affinity Purified Ab

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Anti-Green Fluorescent Protein Antibody (antibody)

RRID:AB_10000240

This polyclonal targets Green Fluorescent Protein (GFP)

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Rat IgG2a, kappa Isotype Control, Alexa Fluor?? 647 Conjugated, Clone R35-95 (antibody)

RRID:AB_396799

This unknown targets Rat IgG2a kappa Isotype Control Alexa Fluor?? 647 Clone R35-95

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Rat IgG2b, k (antibody)

RRID:AB_10049479

This monoclonal targets Rat IgG2b k

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

RRID:AB_479719

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

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RAT IGG2A KPA ITCL FITC 100TST R35-95 (antibody)

RRID:AB_479727

This unknown targets Isotype Control

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

RRID:AB_395508

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

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

RRID:AB_394456

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

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Rat IgG2b, k (antibody)

RRID:AB_10063104

This monoclonal targets Rat IgG2b k

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Lineage Antibody Cocktail, with Isotype Control (antibody)

RRID:AB_10611731

This unknown targets Lineage Cocktail with Isotype Control

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Rat IgG2b, k (antibody)

RRID:AB_1645681

This monoclonal targets Rat IgG2b k

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CD3 Molecular Complex (antibody)

RRID:AB_10679120

This monoclonal targets CD3 Molecular Complex

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TER-119/Erythroid cells (antibody)

RRID:AB_398635

This monoclonal targets TER-119/Erythroid cells

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

RRID:AB_394644

This monoclonal targets Ly-6G and Ly-6C

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CD45 (antibody)

RRID:AB_394611

This monoclonal targets CD45

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

RRID:AB_11074292

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

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ImageJ (software resource)

RRID:SCR_003070

Open source Java based image processing software 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 (software resource)

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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GraphPad Prism (software resource)

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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FlowJo (software resource)

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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B6.Cg-Gt(ROSA)26Sortm14(CAG-tdTomato)Hze/J (organism)

RRID:IMSR_JAX:007914

Mus musculus with name B6.Cg-Gt(ROSA)26Sortm14(CAG-tdTomato)Hze/J from IMSR.

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B6.Cg-Commd10Tg(Vav1-icre)A2Kio/J (organism)

RRID:IMSR_JAX:008610

Mus musculus with name B6.Cg-Commd10Tg(Vav1-icre)A2Kio/J from IMSR.

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B6.FVB-Tg(Cdh5-cre)7Mlia/J (organism)

RRID:IMSR_JAX:006137

Mus musculus with name B6.FVB-Tg(Cdh5-cre)7Mlia/J from IMSR.

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B6.129(Cg)-Leprtm2(cre)Rck/J (organism)

RRID:IMSR_JAX:008320

Mus musculus with name B6.129(Cg)-Leprtm2(cre)Rck/J from IMSR.

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B6.FVB-Tg(BGLAP-cre)1Clem/J (organism)

RRID:IMSR_JAX:019509

Mus musculus with name B6.FVB-Tg(BGLAP-cre)1Clem/J from IMSR.

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B6.SJL-Ptprca Pepc/BoyJ (organism)

RRID:IMSR_JAX:002014

Mus musculus with name B6.SJL-Ptprca Pepc/BoyJ from IMSR.

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C57BL/6J (organism)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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