DOI: 10.1182/blood.v89.10.3624. A Role for the Wnt Gene Family in Hematopoiesis: Expansion of Multilineage Progenitor Cells

A Role for the Wnt Gene Family in Hematopoiesis: Expansion of Multilineage Progenitor Cells

10.1182/blood.v89.10.3624

Crossref journal-article

American Society of Hematology

Blood (234)

Abstract

AbstractThe microenvironment is a key regulator of hematopoietic stem cells (HSCs) and is a likely source of extracellular factors that control stem cell fate. A better understanding of these microenvironmental factors may come from investigations of developmental cell fate determination in which the critical roles of cell-cell interactions of multipotential cells have been shown. The Wnt gene family is known to regulate the cell fate and cell-cell interactions of multipotential cells in a variety of tissues. Expression of Wnts and of their putative receptors encoded by murine homologs of the Drosophila frizzled gene in hematopoietic tissues was examined by reverse transcriptase-polymerase chain reaction. Wnt-5a and Wnt-10b were expressed in day-11 murine yolk sac, day-14 fetal liver, and fetal liver AA4+ cells. The expression profiles of four murine frizzled homologs, Mfz3-7, were nearly identical to that of Wnt-5a and Wnt-10b. Notably, Wnt-10b was expressed in the fetal liver AA4+ Sca+ c-kit+ (flASK) HSC population. A role for Wnts in HSC fate determination was studied by treatment of HSC populations in culture with soluble WNT proteins. The addition of conditioned media from cells transfected with Wnt-1, Wnt-5a, or Wnt-10b cDNAs to cultures of flASK cells stimulated a sevenfold, eightfold, and 11-fold expansion in cell number, respectively, relative to control media. Removal of WNT-5a from this media by immunodepletion depleted the stimulatory activity from the media, whereas addition of a partially purified WNT-5a stimulated a fivefold expansion relative to control cells. Transduction of flASK cells with a retrovirus bearing a Wnt-5a cDNA enhanced proliferation. We conclude that WNTs stimulate the survival/proliferation of hematopoietic progenitors, demonstrating that WNTs comprise a novel class of hematopoietic cell regulators.

Bibliography

Austin, T. W., Solar, G. P., Ziegler, F. C., Liem, L., & Matthews, W. (1997). A Role for the Wnt Gene Family in Hematopoiesis: Expansion of Multilineage Progenitor Cells. Blood, 89(10), 3624â3635.

Authors 5

Timothy W. Austin (first)
Gregg P. Solar (additional)
Francis C. Ziegler (additional)
Linda Liem (additional)
William Matthews (additional)

References 61 Referenced 255

10.1182/blood.V81.11.2844.2844 / Blood / Differentiation and proliferation of hematopoietic stem cells. by Ogawa (1993)
10.1146/annurev.cb.11.110195.000343 / Annu Rev Cell Dev Biol / The biology of hematopoietic stem cells [review]. by Morrison (1995)
10.1073/pnas.89.5.1968 / Proc Natl Acad Sci USA / Proliferation of totipotent hematopoietic stem cells in vitro with retention of long-term competitive in vivo reconstituting ability. by Fraser (1992)
10.1182/blood.V81.2.365.bloodjournal812365 / Blood / Maintenance of high levels of pluripotent hematopoietic stem cells in vitro: Effect of stromal cells and c-kit. by Wineman (1993)
10.1182/blood.V81.12.3463.3463 / Blood / Bone marrow transplantation with interleukin-1 plus kit-ligand ex vivo expanded bone marrow accelerates hematopoietic reconstitution in mice without the loss of stem cell lineage and proliferative potential. by Muench (1993)
10.1182/blood.V83.1.128.128 / Blood / Amplification of Sca-1+ Lin− WGA+ cells in serum-free cultures containing steel factor, interleukin-6, and erythropoietin with maintenance of cells with long-term in vivo reconstituting potential. by Rebel (1994)
10.1182/blood.V81.12.3169.3169 / Blood / Ex vivo expansion of hematopoietic stem and progenitor cells: Robbing Peter to pay Paul? [editorial]. by Williams (1993)
10.1002/stem.5530130505 / Stem Cells / The stromal cells' guide to the stem cell universe. by Muller-Sieburg (1995)
10.1016/1074-7613(94)90081-7 / Immunity / Development of hematopoietic stem cell activity in the mouse embryo. by Muller (1994)
10.1182/blood.V84.8.2422.2422 / Blood / Cellular and molecular characterization of the role of the flk-2/flt-3 receptor tyrosine kinase in hematopoietic stem cells. by Zeigler (1994)
10.1073/pnas.92.22.10302 / Proc Natl Acad Sci USA / The purification and characterization of fetal liver hematopoietic stem cells. by Morrison (1995)
10.1182/blood.V87.8.3500.bloodjournal8783500 / Blood / The repopulation potential of fetal liver hematopoietic stem cells in mice exceeds that of their liver adult bone marrow counterparts. by Rebel (1996)
10.1016/S0168-9525(00)89107-6 / Trends Genet / Mouse embryonic hematopoiesis [review]. by Dzierzak (1995)
10.1182/blood.V86.8.2876.2876 / Blood / Developmental biology of hematopoiesis. by Zon (1995)
10.1126/science.7939714 / Science / Vertebrate embryonic induction: Mesodermal and neural patterning. by Kessler (1994)
10.1016/S0960-9822(02)00432-3 / Curr Biol / Mapping vertebrate embryos. by Tam (1996)
10.1002/bies.950150211 / Bioessays / When cells take fate into their own hands: Differential competence to respond to inducing signals generates diversity in the embryonic mesoderm. by Christian (1993)
10.1101/gad.7.1.13 / Genes Dev / Interactions between Xwnt-8 and Spemann organizer signaling pathways generate dorsoventral pattern in the embryonic mesoderm of Xenopus. by Christian (1993)
10.1242/dev.119.4.1161 / Development / Xwnt-11: A maternally expressed Xenopus wnt gene. by Ku (1993)
10.1073/pnas.89.11.5098 / Proc Natl Acad Sci USA / Diversification of the Wnt gene family on the ancestral lineage of vertebrates. by Sidow (1992)
10.1016/0168-9525(92)90122-K / Trends Genet / The Wnt family of developmental regulators. by McMahon (1992)
10.1016/0092-8674(92)90630-U / Cell / Wnt genes. by Nusse (1992)
10.1128/MCB.10.6.2723 / Mol Cell Biol / Secreted int-1 protein is associated with the cell surface. by Papkoff (1990)
10.1002/j.1460-2075.1990.tb08276.x / EMBO J / The proto-oncogene int-1 encodes a secreted protein associated with the extracellular matrix. by Bradley (1990)
10.1038/382225a0 / Nature / A new member of the frizzled gene family from Drosophila functions as a Wingless receptor. by Bhanot (1996)
10.1016/0092-8674(87)90038-9 / Cell / The Drosophila homolog of the mouse mammary oncogene int-1 is identical to the segment polarity gene wingless. by Rijsewijk (1987)
10.1016/0012-1606(77)90266-4 / Dev Biol / The development of wingless, a homeotic mutation of Drosophila. by Morata (1977)
10.1016/0012-1606(88)90062-0 / Dev Biol / Embryonic and imaginal requirements for wingless, a segment-polarity gene in Drosophila. by Baker (1988)
10.1006/dbio.1994.1325 / Dev Biol / Signaling by wingless in Drosophila. by Klingensmith (1994)
10.1242/dev.120.5.1035 / Development / The Caenorhabditis elegans gene lin-44 controls the polarity of asymmetric cell divisions. by Herman (1994)
10.1016/0092-8674(90)90385-R / Cell / The Wnt-1 (int-1) proto-oncogene is required for development of a large region of the mouse brain. by McMahon (1990)
10.1038/346847a0 / Nature / Targeted disruption of the murine int-1 proto-oncogene resulting in severe abnormalities in midbrain and cerebellar development. by Thomas (1990)
10.1038/372679a0 / Nature / Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt-4. by Stark (1994)
10.1101/gad.8.2.174 / Genes Dev / Wnt-3a regulates somite and tailbud formation in the mouse embryo. by Takada (1994)
10.1038/374350a0 / Nature / Dorsalizing signal Wnt-7a required for normal polarity of D-V and A-P axes of mouse limb. by Parr (1995)
10.1006/dbio.1995.1236 / Dev Biol / Wnt-4 expression induces a pregnancy-like growth pattern in reconstituted mammary glands in virgin mice. by Bradbury (1995)
10.1242/dev.122.3.823 / Development / In vitro analysis of epiblast potency for hematopoietic cell differentiation. by Kanatsu (1996)
10.1101/gad.4.12b.2319 / Genes Dev / Expression of multiple novel Wnt-1/int-1-related genes during fetal and adult mouse development. by Gavin (1990)
10.1242/dev.119.1.247 / Development / Mouse Wnt genes exhibit discrete domains of expression in the early embryonic CNS and limb buds. by Parr (1993)
10.1074/jbc.270.52.31225 / J Biol Chem / Characterization of the complete genomic structure of the human WNT-5A gene, functional analysis of its promoter, chromosomal mapping, and expression in early human embryogenesis. by Danielson (1995)
10.1073/pnas.92.6.2268 / Proc Natl Acad Sci USA / Insertional mutagenesis identifies a member of the Wnt gene family as a candidate oncogene in the mammary epithelium of int-2/Fgf-3 transgenic mice. by Lee (1995)
10.1016/0003-2697(87)90021-2 / Anal Biochem / Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. by Chomczynski (1987)
{'key': '2019112009550347500_B43'}
10.1073/pnas.92.4.1142 / Proc Natl Acad Sci USA / Expression cloning of cardiotrophin 1, a cytokine that induces cardiac myocyte hypertrophy. by Pennica (1995)
10.1128/MCB.11.12.5848 / Mol Cell Biol / The encephalomyocarditis virus internal ribosome entry site allows efficient coexpression of two genes from a recombinant provirus in cultured cells and in embryos. by Ghattas (1991)
10.1073/pnas.90.18.8392 / Proc Natl Acad Sci USA / Production of high-titer helper-free retroviruses by transient transfection. by Pear (1993)
10.1089/hum.1996.7.3-343 / Hum Gene Ther / A rapid and quantitative assay to estimate gene transfer into hematopoietic stem/progenitor cells using a 96-well format PCR and fluorescent detection system univeral for MMLV-based provirus. by Gerard (1996)
10.1093/protein/3.6.547 / Protein Eng / Mammalian cell transient expression of tissue factor for the production of antigen. by Paborsky (1990)
10.1074/jbc.271.8.4468 / J Biol Chem / A large family of putative transmembrane receptors homologous to the product of the drosophila tissue polarity gene frizzled. by Wang (1996)
10.1182/blood.V78.4.914.914 / Blood / Effects of hematopoietic growth factors on the survival of primitive stem cells in liquid suspension culture. by Bodine (1991)
{'key': '2019112009550347500_B51'}
10.1016/0092-8674(90)90300-4 / Cell / Identification, purification, and biological characterization of hematopoietic stem cell factor from buffalo rat liver–conditioned medium. by Zsebo (1990)
{'key': '2019112009550347500_B53'}
10.1083/jcb.124.5.729 / J Cell Biol / Wnt-1 modulates cell-cell adhesion in mammalian cells by stabilizing beta-catenin binding to the cell adhesion protein cadherin. by Hinck (1994)
10.1038/352438a0 / Nature / Fibronectin and VLA-4 in haematopoietic stem cell-microenvironment interactions. by Williams (1991)
10.1038/347667a0 / Nature / Embryonic expression of a haematopoietic growth factor encoded by the Sl locus and the ligand for c-kit. by Matsui (1990)
10.1002/j.1460-2075.1991.tb07782.x / EMBO J / Embryonic RNA expression patterns of the c-kit receptor and its cognate ligand suggest multiple functional roles in mouse development. by Keshet (1991)
10.1002/cyto.990120402 / Cytometry / Improved FACS-Gal: Flow cytometric analysis and sorting of viable eukaryotic cells expressing reporter gene constructs. by Fiering (1991)
10.1038/368342a0 / Nature / Biological activity of soluble wingless protein in cultured Drosophila imaginal disc cells. by van Leeuwen (1994)
10.1128/MCB.15.8.4616 / Mol Cell Biol / A soluble form of Wnt-1 protein with mitogenic activity on mammary epithelial cells. by Bradley (1995)
10.1016/0925-4773(95)00383-5 / Mech Dev / Murine Wnt-11 and Wnt-12 have temporally and spatially restricted expression patterns during embryonic development. by Christiansen (1995)

Dates

Type	When
Created	5 years, 10 months ago (Oct. 14, 2019, 5:11 a.m.)
Deposited	2 years, 11 months ago (Oct. 1, 2022, 1:49 p.m.)
Indexed	1 hour, 7 minutes ago (Sept. 2, 2025, 7:58 p.m.)
Issued	28 years, 3 months ago (May 15, 1997)
Published	28 years, 3 months ago (May 15, 1997)
Published Print	28 years, 3 months ago (May 15, 1997)

Funders 0

None

BibTeX

@article{Austin_1997, title={A Role for the Wnt Gene Family in Hematopoiesis: Expansion of Multilineage Progenitor Cells}, volume={89}, ISSN={0006-4971}, url={http://dx.doi.org/10.1182/blood.v89.10.3624}, DOI={10.1182/blood.v89.10.3624}, number={10}, journal={Blood}, publisher={American Society of Hematology}, author={Austin, Timothy W. and Solar, Gregg P. and Ziegler, Francis C. and Liem, Linda and Matthews, William}, year={1997}, month=may, pages={3624–3635} }

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      "volume": "89",
      "author": "Fraser",
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      "article-title": "Maintenance of high levels of pluripotent hematopoietic stem cells in vitro: Effect of stromal cells and c-kit.",
      "volume": "81",
      "author": "Wineman",
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      "journal-title": "Blood"
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      "article-title": "Bone marrow transplantation with interleukin-1 plus kit-ligand ex vivo expanded bone marrow accelerates hematopoietic reconstitution in mice without the loss of stem cell lineage and proliferative potential.",
      "volume": "81",
      "author": "Muench",
      "year": "1993",
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      "volume": "83",
      "author": "Rebel",
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      "key": "2019112009550347500_B22",
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      "first-page": "1073",
      "DOI": "10.1016/0092-8674(92)90630-U",
      "article-title": "Wnt genes.",
      "volume": "69",
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      "volume": "382",
      "author": "Bhanot",
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      "author": "Rijsewijk",
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      "volume": "56",
      "author": "Morata",
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      "volume": "125",
      "author": "Baker",
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      "author": "Klingensmith",
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      "author": "McMahon",
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      "volume": "346",
      "author": "Thomas",
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      "author": "Takada",
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      "volume": "122",
      "author": "Kanatsu",
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      "volume": "4",
      "author": "Gavin",
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      "volume": "270",
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      "author": "Chomczynski",
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      "volume": "11",
      "author": "Ghattas",
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      "volume": "7",
      "author": "Gerard",
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      "author": "Paborsky",
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      "volume": "271",
      "author": "Wang",
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      "author": "Bodine",
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