Characterization of mouse lymphohematopoietic stem cells lacking spleen colony-forming activity

Richard J Jones, Michael I. Collector, James P. Barber, Milada S. Vala, Mary Jo Fackler, W. Stratford May, Constance A. Griffin, Anita L. Hawkins, Barbara A. Zehnbauer, John Hilton, O. Michael Colvin, Saul J. Sharkis

Research output: Contribution to journalArticle

Abstract

The classical definition of lymphohematopoietic stem cells (LHSC), the most primitive progenitors of all blood cells, requires that they have the capacity for self-renewal and for the long-term production of all blood cell lineages. However, other characteristics of LHSC have been debated. Our previous data suggested that mouse LHSC are very slowly proliferating cells that generate delayed multilineage engraftment, while 'radioprotection' (rapid engraftment that will prevent early death from radiation-induced marrow aplasia) results from more committed progenitors. Alternatively, some groups have reported that mouse LHSC are responsible for both radioprotection and long-term repopulation of all blood cell lineages. A possible explanation for this difference is that cells with the capacity for long-term production of all blood cell lineages are biologically heterogeneous. We now show that 10 LHSC can generate all blood cell lineages for the lifetime of the animal. However, these cells lacked radioprotection and spleen colony-forming activity. LHSC were identified and isolated by their small size, their lack of expression of antigens characteristic of mature blood cell lineages, and their high expression of aldehyde dehydrogenase. In addition, these cells were found to express undetectable or low levels of many antigens presumed to mark LHSC, including Thy-1, Ly-6A/E (Sca-1), c-kit, and CD34. There appears to be at least two classes of LHSC with the capacity for long-term production of all blood cell lineages: one that generates both radioprotection and long- term engraftment and one that produces delayed but durable engraftment. Our data suggest that this latter class may represent a very primitive class of LHSC.

Original languageEnglish (US)
Pages (from-to)487-491
Number of pages5
JournalBlood
Volume88
Issue number2
StatePublished - Jul 15 1996

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Stem cells
Stem Cells
Spleen
Cell Lineage
Blood Cells
Blood
Cells
Antigens
Aldehyde Dehydrogenase
Animals
Bone Marrow
Radiation

ASJC Scopus subject areas

  • Hematology

Cite this

Jones, R. J., Collector, M. I., Barber, J. P., Vala, M. S., Fackler, M. J., May, W. S., ... Sharkis, S. J. (1996). Characterization of mouse lymphohematopoietic stem cells lacking spleen colony-forming activity. Blood, 88(2), 487-491.

Characterization of mouse lymphohematopoietic stem cells lacking spleen colony-forming activity. / Jones, Richard J; Collector, Michael I.; Barber, James P.; Vala, Milada S.; Fackler, Mary Jo; May, W. Stratford; Griffin, Constance A.; Hawkins, Anita L.; Zehnbauer, Barbara A.; Hilton, John; Colvin, O. Michael; Sharkis, Saul J.

In: Blood, Vol. 88, No. 2, 15.07.1996, p. 487-491.

Research output: Contribution to journalArticle

Jones, RJ, Collector, MI, Barber, JP, Vala, MS, Fackler, MJ, May, WS, Griffin, CA, Hawkins, AL, Zehnbauer, BA, Hilton, J, Colvin, OM & Sharkis, SJ 1996, 'Characterization of mouse lymphohematopoietic stem cells lacking spleen colony-forming activity', Blood, vol. 88, no. 2, pp. 487-491.
Jones RJ, Collector MI, Barber JP, Vala MS, Fackler MJ, May WS et al. Characterization of mouse lymphohematopoietic stem cells lacking spleen colony-forming activity. Blood. 1996 Jul 15;88(2):487-491.
Jones, Richard J ; Collector, Michael I. ; Barber, James P. ; Vala, Milada S. ; Fackler, Mary Jo ; May, W. Stratford ; Griffin, Constance A. ; Hawkins, Anita L. ; Zehnbauer, Barbara A. ; Hilton, John ; Colvin, O. Michael ; Sharkis, Saul J. / Characterization of mouse lymphohematopoietic stem cells lacking spleen colony-forming activity. In: Blood. 1996 ; Vol. 88, No. 2. pp. 487-491.
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abstract = "The classical definition of lymphohematopoietic stem cells (LHSC), the most primitive progenitors of all blood cells, requires that they have the capacity for self-renewal and for the long-term production of all blood cell lineages. However, other characteristics of LHSC have been debated. Our previous data suggested that mouse LHSC are very slowly proliferating cells that generate delayed multilineage engraftment, while 'radioprotection' (rapid engraftment that will prevent early death from radiation-induced marrow aplasia) results from more committed progenitors. Alternatively, some groups have reported that mouse LHSC are responsible for both radioprotection and long-term repopulation of all blood cell lineages. A possible explanation for this difference is that cells with the capacity for long-term production of all blood cell lineages are biologically heterogeneous. We now show that 10 LHSC can generate all blood cell lineages for the lifetime of the animal. However, these cells lacked radioprotection and spleen colony-forming activity. LHSC were identified and isolated by their small size, their lack of expression of antigens characteristic of mature blood cell lineages, and their high expression of aldehyde dehydrogenase. In addition, these cells were found to express undetectable or low levels of many antigens presumed to mark LHSC, including Thy-1, Ly-6A/E (Sca-1), c-kit, and CD34. There appears to be at least two classes of LHSC with the capacity for long-term production of all blood cell lineages: one that generates both radioprotection and long- term engraftment and one that produces delayed but durable engraftment. Our data suggest that this latter class may represent a very primitive class of LHSC.",
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