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Identification of a lineage of multipotent hematopoietic progenitors

Morrison, Sean J. and Wandycz, Antoni M. and Hemmanti, Houman D. and Wright, Douglas E. and Weissman, Irving L. (1997) Identification of a lineage of multipotent hematopoietic progenitors. Development, 124 (10). pp. 1929-1939. ISSN 0950-1991.

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All multipotent hematopoietic progenitors in C57BL-Thy-1.1 bone marrow are divided among three subpopulations of Thy-1.1^(lo) Sca-1^+ Lin^(-/lo) c-kit^+ cells: long-term reconstituting Mac-1^-CD4^-c-kit^+ cells and transiently reconstituting Mac-1^(lo)CD4^-or Mac-1^(lo) CD4^(lo) 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-1^(lo)CD4^- cells, which gave rise to Mac-1^(lo)CD4^(lo) cells. Mac-1^- CD4^-c-kit^+ cells had long-term self-renewal potential, with each cell being capable of giving rise to more than 10^4 functionally similar Mac-1^-CD4^-c-kit^+ cells. At least half of Mac-1^(lo)CD4^- cells had transient self-renewal potential, detected in the spleen 7 days after reconstitution. Mac-1^(lo)CD4^(lo) 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.

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Additional Information:© 1997 The Company of Biologists Limited. Accepted 6 March 1997. We thank Libuse Jerabek for laboratory management, Tim Knaak and Jack Sun for FACS machine operation, Veronica Braunstein and Andraea Nicolau for antibody preparation, Lucino Hidalgo and Ricardo Salazaar for animal care. Thanks to Koichi Akashi for expert assistance with methylcellulose assays. S. J. M. was a Howard Hughes Medical Institute Predoctoral Fellow. D. E. W. is a Howard Hughes Medical Institute Medical Student Fellow. This work was supported by National Cancer Institute Grant CA42551.
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National Cancer InstituteCA-42551
Subject Keywords:hematopoietic stem cell, lineage, transplantation, self renewal, bone marrow, blood, stem cell
Issue or Number:10
Record Number:CaltechAUTHORS:20120130-090914513
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Official Citation: S.J. Morrison, A.M. Wandycz, H.D. Hemmati, D.E. Wright, and I.L. Weissman Identification of a lineage of multipotent hematopoietic progenitors Development 1997 124:1929-1939
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:29015
Deposited By: Ruth Sustaita
Deposited On:30 Jan 2012 17:38
Last Modified:03 Oct 2019 03:37

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