PDGFRα and CD51 mark human Nestin+ sphere-forming mesenchymal stem cells capable of hematopoietic progenitor cell expansion

Pinho, Sandra; Lacombe, Julie; Hanoun, Maher; Mizoguchi, Takahiro; Bruns, Ingmar; Kunisaki, Yuya; Frenette, Paul S.

doi:10.1084/jem.20122252

Cited by 443 publications

(504 citation statements)

References 42 publications

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“…5D). In addition, we observed no difference in MS/PC frequency as defined by the PDGFRa + CD51 + CD31 -CD45 -Lin -phenotype [36] (Fig. 5E, F) or the PDGFRa + Sca1 + CD31 -CD45 -Lin -phenotype [37] in Col1a1CreSHIP flox/flox as compared to SHIP flox/flox controls ( Supplementary Fig.…”

Section: Ship1 Expression In Mature Osteolineage Cells Is Not Requirementioning

confidence: 80%

“…Thus, we analyzed the frequency of MSC by two well-validated phenotypes where single cell cloning assays have confirmed that these cell populations are highly enriched for multipotent cells capable of selfrenewal [36]. Multi-parameter flow cytometry analysis showed that MSC of the PDGFRa + CD51 + CD31 -CD45 -Lin -phenotype (Fig.…”

Section: Mice With Ablation Of Ship1 In Ms/pc Exhibit Impaired Growthmentioning

confidence: 98%

“…PDGFRa + CD51 + MSC [36] and PDGFRa + Sca1 + MSC [37] were detected using methods and reagents as described by Winkler et al [38], Schepers et al [39], Morikawa et al [37], Houlihan et al [40] and Pinho et al [36]. Femurs, tibias, humeri, ulnas, radii, and pelvis were dissected.…”

Section: In Vivo Msc Immunophenotyping By Flow Cytometrymentioning

confidence: 99%

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SHIP1 Regulates MSC Numbers and Their Osteolineage Commitment by Limiting Induction of the PI3K/Akt/β-Catenin/Id2 Axis

Iyer

Viernes

Chisholm³

et al. 2014

Stem Cells and Development

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Here, we show that Src homology 2-domain-containing inositol 5¢-phosphatase 1 (SHIP1) is required for the efficient development of osteoblasts from mesenchymal stem cells (MSCs) such that bone growth and density are reduced in mice that lack SHIP1 expression in MSCs. We find that SHIP1 promotes the osteogenic output of MSCs by limiting activation of the PI3K/Akt/b-catenin pathway required for induction of the MSC stemness factor Id2. In parallel, we demonstrate that mice with myeloid-restricted ablation of SHIP1, including osteoclasts (OCs), show no reduction in bone mass or density. Hence, diminished bone mass and density in the SHIP1-deficient mice results from SHIP deficiency in MSC and osteolineage progenitors. Intriguingly, mice with a SHIP-deficient MSC compartment also exhibit decreased OC numbers. In agreement with our genetic findings we also show that treatment of mice with an SHIP1 inhibitor (SHIPi) significantly reduces bone mass. These findings demonstrate a novel role for SHIP1 in MSC fate determination and bone growth. Further, SHIPi may represent a novel therapeutic approach to limit bone development in osteopetrotic and sclerotic bone diseases.

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Section: Ship1 Expression In Mature Osteolineage Cells Is Not Requirementioning

confidence: 80%

Section: Mice With Ablation Of Ship1 In Ms/pc Exhibit Impaired Growthmentioning

confidence: 98%

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SHIP1 Regulates MSC Numbers and Their Osteolineage Commitment by Limiting Induction of the PI3K/Akt/β-Catenin/Id2 Axis

Iyer

Viernes

Chisholm³

et al. 2014

Stem Cells and Development

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“…Nestin+ perivascular cells are additional candidate niche cells of the mesenchymal cell type, which express PDGFRα and CD51 [21]. By crossing the Cre-recombinase-inducible diphtheria toxin receptor mice (iDTR) with Nestin-Cre mice, researchers could selectively eliminate Nestin+ perivascular cells by treating the mice with tamoxifen and diphtheria toxin.…”

Section: Niche Cells Regulating Hscsmentioning

confidence: 99%

Mechanisms of self-renewal in hematopoietic stem cells

Wang

Ema

2015

Int J Hematol

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“…12,[20][21][22][23] However, as stated above, in addition to HSCs/MPPs, SRC activities were also found within LMPP fractions lacking erythro-myeloid differentiation potentials. 4,5 Furthermore, by comparing engraftment potentials of retrovirally marked baboon primitive haematopoietic cells in NOD/SCID mice and baboon, we previously provided evidence that cells other than true long term repopulating HSCs/MPPs are read out in the NOD/SCID xenotransplantation model.…”

Section: Discussionmentioning

confidence: 65%

Human mesenchymal and murine stromal cells support human lympho-myeloid progenitor expansion but not maintenance of multipotent haematopoietic stem and progenitor cells

et al. 2016

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A major goal in haematopoietic stem cell (HSC) research is to define conditions for the expansion of HSCs or multipotent progenitor cells (MPPs). Since human HSCs/MPPs cannot be isolated, NOD/SCID repopulating cell (SRC) assays emerged as the standard for the quantification of very primitive haematopoietic cell. However, in addition to HSCs/MPPs, lympho-myeloid primed progenitors (LMPPs) were recently found to contain SRC activities, challenging this assay as clear HSC/MPP readout. Because our revised model of human haematopoiesis predicts that HSCs/MPPs can be identified as CD133 C CD34 C cells containing erythroid potentials, we investigated the potential of human mesenchymal and conventional murine stromal cells to support expansion of HSCs/MPPs. Even though all stromal cells supported expansion of CD133 C CD34 C progenitors with long-term myeloid and long-term lymphoid potentials, erythroid potentials were exclusively found within erythro-myeloid CD133 low CD34 C cell fractions. Thus, our data demonstrate that against the prevailing assumption co-cultures on human mesenchymal and murine stromal cells neither promote expansion nor maintenance of HSCs and MPPs.

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PDGFRα and CD51 mark human Nestin+ sphere-forming mesenchymal stem cells capable of hematopoietic progenitor cell expansion

Abstract: A subset of human Nestin+ mesenchymal stem cells expresses PDGFRα and CD51, and these markers can be used for prospective isolation of these cells.

Cited by 443 publications

References 42 publications

SHIP1 Regulates MSC Numbers and Their Osteolineage Commitment by Limiting Induction of the PI3K/Akt/β-Catenin/Id2 Axis

SHIP1 Regulates MSC Numbers and Their Osteolineage Commitment by Limiting Induction of the PI3K/Akt/β-Catenin/Id2 Axis

Mechanisms of self-renewal in hematopoietic stem cells

Human mesenchymal and murine stromal cells support human lympho-myeloid progenitor expansion but not maintenance of multipotent haematopoietic stem and progenitor cells

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