Asymmetric Cell Divisions Sustain Long-Term Hematopoiesis from Single-sorted Human Fetal Liver Cells

Brummendorf, Tim H.; Dragowska, Wieslawa; Zijlmans, J.Mark J.M.; Thornbury, Gayle; Lansdorp, Peter M.

doi:10.1084/jem.188.6.1117

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Article| September 21 1998

Asymmetric Cell Divisions Sustain Long-Term Hematopoiesis from Single-sorted Human Fetal Liver Cells

Tim H. Brummendorf,

Tim H. Brummendorf

From the *Terry Fox Laboratory, British Columbia Cancer Research Centre, Vancouver, British Columbia, V5Z 1L3, Canada; the ‡Institute of Hematology, Erasmus University, 3000 DR, Rotterdam, The Netherlands; and the §Department of Medicine, University of British Columbia, Vancouver, British Columbia, V6T 2B5, Canada

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Wieslawa Dragowska,

Wieslawa Dragowska

From the *Terry Fox Laboratory, British Columbia Cancer Research Centre, Vancouver, British Columbia, V5Z 1L3, Canada; the ‡Institute of Hematology, Erasmus University, 3000 DR, Rotterdam, The Netherlands; and the §Department of Medicine, University of British Columbia, Vancouver, British Columbia, V6T 2B5, Canada

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J.Mark J.M. Zijlmans,

J.Mark J.M. Zijlmans

From the *Terry Fox Laboratory, British Columbia Cancer Research Centre, Vancouver, British Columbia, V5Z 1L3, Canada; the ‡Institute of Hematology, Erasmus University, 3000 DR, Rotterdam, The Netherlands; and the §Department of Medicine, University of British Columbia, Vancouver, British Columbia, V6T 2B5, Canada

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Gayle Thornbury,

Gayle Thornbury

From the *Terry Fox Laboratory, British Columbia Cancer Research Centre, Vancouver, British Columbia, V5Z 1L3, Canada; the ‡Institute of Hematology, Erasmus University, 3000 DR, Rotterdam, The Netherlands; and the §Department of Medicine, University of British Columbia, Vancouver, British Columbia, V6T 2B5, Canada

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Peter M. Lansdorp

From the *Terry Fox Laboratory, British Columbia Cancer Research Centre, Vancouver, British Columbia, V5Z 1L3, Canada; the ‡Institute of Hematology, Erasmus University, 3000 DR, Rotterdam, The Netherlands; and the §Department of Medicine, University of British Columbia, Vancouver, British Columbia, V6T 2B5, Canada

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Author and Article Information

Tim H. Brummendorf

From the *Terry Fox Laboratory, British Columbia Cancer Research Centre, Vancouver, British Columbia, V5Z 1L3, Canada; the ‡Institute of Hematology, Erasmus University, 3000 DR, Rotterdam, The Netherlands; and the §Department of Medicine, University of British Columbia, Vancouver, British Columbia, V6T 2B5, Canada

Wieslawa Dragowska

From the *Terry Fox Laboratory, British Columbia Cancer Research Centre, Vancouver, British Columbia, V5Z 1L3, Canada; the ‡Institute of Hematology, Erasmus University, 3000 DR, Rotterdam, The Netherlands; and the §Department of Medicine, University of British Columbia, Vancouver, British Columbia, V6T 2B5, Canada

J.Mark J.M. Zijlmans

From the *Terry Fox Laboratory, British Columbia Cancer Research Centre, Vancouver, British Columbia, V5Z 1L3, Canada; the ‡Institute of Hematology, Erasmus University, 3000 DR, Rotterdam, The Netherlands; and the §Department of Medicine, University of British Columbia, Vancouver, British Columbia, V6T 2B5, Canada

Gayle Thornbury

From the *Terry Fox Laboratory, British Columbia Cancer Research Centre, Vancouver, British Columbia, V5Z 1L3, Canada; the ‡Institute of Hematology, Erasmus University, 3000 DR, Rotterdam, The Netherlands; and the §Department of Medicine, University of British Columbia, Vancouver, British Columbia, V6T 2B5, Canada

Peter M. Lansdorp

From the *Terry Fox Laboratory, British Columbia Cancer Research Centre, Vancouver, British Columbia, V5Z 1L3, Canada; the ‡Institute of Hematology, Erasmus University, 3000 DR, Rotterdam, The Netherlands; and the §Department of Medicine, University of British Columbia, Vancouver, British Columbia, V6T 2B5, Canada

Address correspondence to Peter Lansdorp, Terry Fox Laboratory, BC Cancer Research Centre, 601 West 10th Ave., Vancouver, BC, V5Z 1L3, Canada. Phone: 604-877-6070, ext. 3026; Fax: 604-877-0712; E-mail: [email protected]

Received: May 08 1998

Revision Received: June 22 1998

Online ISSN: 1540-9538

Print ISSN: 0022-1007

1998

J Exp Med (1998) 188 (6): 1117–1124.

https://doi.org/10.1084/jem.188.6.1117

Hematopoietic stem cells (HSCs) in adult marrow are believed to be derived from fetal liver precursors. To study cell kinetics involved in long-term hematopoiesis, we studied single-sorted candidate HSCs from fetal liver that were cultured in the presence of a mixture of stimulatory cytokines. After 8–10 d, the number of cells in primary cultures varied from <100 to >10,000 cells. Single cells in slow growing colonies were recloned upon reaching a 100–200 cell stage. Strikingly, the number of cells in subclones varied widely again. These results are indicative of asymmetric divisions in primitive hematopoietic cells in which proliferative potential and cell cycle properties are unevenly distributed among daughter cells. The continuous generation of functional heterogeneity among the clonal progeny of HSCs is in support of intrinsic control of stem cell fate and provides a model for the long-term maintenance of hematopoiesis in vitro and in vivo.

1998

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