DOI: 10.1242/dev.124.10.1929. Identification of a lineage of multipotent hematopoietic progenitors

Identification of a lineage of multipotent hematopoietic progenitors

10.1242/dev.124.10.1929

Crossref journal-article

The Company of Biologists

Development (237)

Abstract

ABSTRACT All multipotent hematopoietic progenitors in C57BL-Thy-1.1 bone marrow are divided among three subpopulations of Thy-1.1loSca-1+Lin−/loc-kit+cells:long-term reconstituting Mac-1−CD4−c-kit+ cells and transiently reconstituting Mac-1loCD4− or Mac-1loCD4lo cells. This study shows that the same populations, with similar functional activities, exist in mice whose hematopoietic systems were reconstituted by hematopoietic stem cells after lethal irradiation. We demonstrate that these populations form a lineage of multipotent progenitors from long-term self-renewing stem cells to the most mature multipotent progenitor population. In reconstituted mice, Mac-1−CD4−c-kit+ cells gave rise to Mac-1loCD4− cells, which gave rise to Mac-1loCD4lo cells. Mac-1−CD4−c-kit+ cells had long-term self-renewal potential, with each cell being capable of giving rise to more than 104 functionally similar Mac-1−CD4−c-kit+ cells. At least half of Mac-1loCD4− cells had transient self-renewal potential, detected in the spleen 7 days after reconstitution. Mac-1loCD4lo cells did not have detectable self-renewal potential. The identification of a lineage of multipotent progenitors provides an important tool for identifying genes that regulate self-renewal and lineage commitment.

Bibliography

Morrison, S. J., Wandycz, A. M., Hemmati, H. D., Wright, D. E., & Weissman, I. L. (1997). Identification of a lineage of multipotent hematopoietic progenitors. Development, 124(10), 1929â1939.

Authors 5

Sean J. Morrison (first)
Antoni M. Wandycz (additional)
Houman D. Hemmati (additional)
Douglas E. Wright (additional)
Irving L. Weissman (additional)

References 27 Referenced 322

10.1182/blood.V19.6.702.702 / Blood / Evidence for stem cells in the peripheral blood of mice by Goodman (1962)
10.1084/jem.172.3.835 / J. Exp. Med / T cell receptor-mediated negative selection of autoreactive T lymphocyte precursors occurs after commitment to the CD4 or CD8 lineages by Guidos (1990)
10.1084/jem.173.5.1213 / J. Exp. Med / Resolution and characterization of pro-B and pre-pro-B cell stages in normal mouse bone marrow by Hardy (1991)
10.1073/pnas.88.21.9902 / Proc. Natl. Acad. Sci., USA / The in vitro response of phenotypically defined mouse stem cells and myeloerythroid progenitors to single or multiple growth factors by Heimfeld (1991)
10.1073/pnas.75.1.490 / Proc. Natl. Acad. Sci., USA / Proliferative capacity of murine hematopoietic stem cells by Hellman (1978)
{'key': '2025021403022262700_DEVELOP_124_10_1929C6', 'first-page': '138', 'volume-title': 'Selected Methods in Cellular Immunology’', 'author': 'Henry', 'year': '1980'} / Selected Methods in Cellular Immunology’ by Henry (1980)
10.1016/S0140-6736(65)90763-4 / Lancet / How many cell-generations? by Kay (1965)
10.1084/jem.178.1.265 / J. Exp. Med / Differentiation of CD3-4-8-human fetal thymocytes in vivo: characterization of a CD3-4+8-intermediate by Kraft (1993)
10.1016/B978-0-12-155050-9.50036-5 / Stem Cells of Renewing Cell Populations by Micklem (1976)
10.1016/S1074-7613(00)80316-7 / Immunity / Telomerase activity in hematopoietic cells is associated with self-renewal potential by Morrison (1996)
10.1146/annurev.cb.11.110195.000343 / Annual Reviews in Cell and Developmental Biology / The biology of hematopoietic stem cells by Morrison (1995)
10.1038/nm0996-1011 / Nature Medicine / The aging of hematopoietic stem cells by Morrison (1996)
10.1016/1074-7613(94)90037-X / Immunity / The long-term repopulating subset of hematopoietic stem cells is deterministic and isolatable by phenotype by Morrison (1994)
10.1073/pnas.94.5.1908 / Proc. Natl. Acad. Sci., USA / Cyclophosphamide/G-CSF induces hematopoietic stem cells to proliferate prior to mobilization by Morrison (1997)
10.1084/jem.183.3.1141 / J. Exp. Med / Genetic control of the frequency of hematopoietic stem cells in mice: mapping of a candidate locus to chromosome 1 by Muller-Sieburg (1996)
10.4049/jimmunol.156.9.3207 / J. Immunol / In vivo self-renewal of c-kit+ Sca-1+ Linlow/-hemopoietic stem cells by Osawa (1996)
10.1016/S0076-6879(84)08086-1 / Methods in Enzymology / Fluorescence activated cell sorting: theory, experimental optimization, and applications in lymphoid cell biology by Parks (1984)
{'key': '2025021403022262700_DEVELOP_124_10_1929C18', 'first-page': '17', 'article-title': 'Organization of haemopoietic stem cells: the generation age hypothesis', 'volume': '12', 'author': 'Rosendaal', 'year': '1979', 'journal-title': 'Cell and Tissue Kinetics'} / Cell and Tissue Kinetics / Organization of haemopoietic stem cells: the generation age hypothesis by Rosendaal (1979)
10.1016/0952-7915(92)90003-W / Current Opinion in Immunology / Cellular aspects of early T-cell development by Shortman (1992)
10.1002/jcp.1030620313 / J. Cell. Comp. Physiol / The distribution of colony-forming cells among spleen colonies by Siminovitch (1963)
{'key': '2025021403022262700_DEVELOP_124_10_1929C21', 'first-page': '82', 'article-title': 'Distribution of injected 59Fe in mice', 'volume': '20', 'author': 'Smith', 'year': '1970', 'journal-title': 'Experimental Hematology'} / Experimental Hematology / Distribution of injected 59Fe in mice by Smith (1970)
10.1182/blood.V85.4.1006.bloodjournal8541006 / Blood / Long-term repopulation of irradiated mice with limiting numbers of purified hematopoietic stem cells: in vivo expansion of stem cell phenotype but not function by Spangrude (1995)
10.1126/science.2898810 / Science / Purification and characterization of mouse hematopoietic stem cells by Spangrude (1988)
10.1182/blood.V79.11.2855.2855 / Blood / Enhancement of murine hematopoiesis by synergistic interactions between steel factor (ligand for c-kit), interleukin-11, and other early acting factors in culture by Tsuji (1992)
10.1182/blood.V83.12.3758.3758 / Blood / Rapid and sustained hematopoietic recovery in lethally irradiated mice transplanted with purified Thy-1.1lo Lin −Sca-1+ hematopoietic stem cells by Uchida (1994)
10.1084/jem.175.1.175 / J Exp Med / Searching for hematopoietic stem cells: evidence that Thy-1.1lo Lin −Sca-1+ cells are the only stem cells in C57BL/Ka-Thy-1.1 bone marrow by Uchida (1992)
10.1084/jem.184.3.903 / J. Exp. Med / Thymic dendritic cell precursors: relationship to the T lymphocyte lineage and phenotype of the dendritic cell progeny by Wu (1996)

Dates

Type	When
Created	4 years, 4 months ago (April 23, 2021, 3:01 p.m.)
Deposited	6 months, 3 weeks ago (Feb. 13, 2025, 10:02 p.m.)
Indexed	2 weeks ago (Aug. 22, 2025, 1:05 a.m.)
Issued	28 years, 3 months ago (May 15, 1997)
Published	28 years, 3 months ago (May 15, 1997)
Published Online	28 years, 3 months ago (May 15, 1997)
Published Print	28 years, 3 months ago (May 15, 1997)

Funders 0

None

BibTeX

@article{Morrison_1997, title={Identification of a lineage of multipotent hematopoietic progenitors}, volume={124}, ISSN={1477-9129}, url={http://dx.doi.org/10.1242/dev.124.10.1929}, DOI={10.1242/dev.124.10.1929}, number={10}, journal={Development}, publisher={The Company of Biologists}, author={Morrison, Sean J. and Wandycz, Antoni M. and Hemmati, Houman D. and Wright, Douglas E. and Weissman, Irving L.}, year={1997}, month=may, pages={1929–1939} }

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  "abstract": "<jats:title>ABSTRACT</jats:title>\n               <jats:p>All multipotent hematopoietic progenitors in C57BL-Thy-1.1 bone marrow are divided among three subpopulations of Thy-1.1loSca-1+Lin\u2212/loc-kit+cells:long-term reconstituting Mac-1\u2212CD4\u2212c-kit+ cells and transiently reconstituting Mac-1loCD4\u2212 or Mac-1loCD4lo cells. This study shows that the same populations, with similar functional activities, exist in mice whose hematopoietic systems were reconstituted by hematopoietic stem cells after lethal irradiation. We demonstrate that these populations form a lineage of multipotent progenitors from long-term self-renewing stem cells to the most mature multipotent progenitor population. In reconstituted mice, Mac-1\u2212CD4\u2212c-kit+ cells gave rise to Mac-1loCD4\u2212 cells, which gave rise to Mac-1loCD4lo cells. Mac-1\u2212CD4\u2212c-kit+ cells had long-term self-renewal potential, with each cell being capable of giving rise to more than 104 functionally similar Mac-1\u2212CD4\u2212c-kit+ cells. At least half of Mac-1loCD4\u2212 cells had transient self-renewal potential, detected in the spleen 7 days after reconstitution. Mac-1loCD4lo cells did not have detectable self-renewal potential. The identification of a lineage of multipotent progenitors provides an important tool for identifying genes that regulate self-renewal and lineage commitment.</jats:p>",
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      "URL": "https://journals.biologists.com/dev/article/124/10/1929/39225/Identification-of-a-lineage-of-multipotent"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        1997,
        5,
        15
      ]
    ]
  },
  "references-count": 27,
  "journal-issue": {
    "issue": "10",
    "published-print": {
      "date-parts": [
        [
          1997,
          5,
          15
        ]
      ]
    }
  },
  "URL": "http://dx.doi.org/10.1242/dev.124.10.1929",
  "relation": {},
  "ISSN": [
    "0950-1991",
    "1477-9129"
  ],
  "subject": [],
  "published": {
    "date-parts": [
      [
        1997,
        5,
        15
      ]
    ]
  }
}