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Progenitor cells divide symmetrically to generate new colony‐forming cells and clonal heterogeneity
Author(s) -
Marley Stephen B.,
Lewis John L.,
Gordon Myrtle Y.
Publication year - 2003
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2003.04338.x
Subject(s) - progenitor cell , clonogenic assay , biology , immunology , interleukin 3 , progenitor , stem cell , population , myeloid , haematopoiesis , cell culture , microbiology and biotechnology , genetics , t cell , medicine , antigen presenting cell , immune system , environmental health
Summary. Self‐renewal is the most fundamental property of haemopoietic stem and progenitor cells. However, because of the need to produce differentiated cells, not all cell divisions involve self‐renewal. We have used a colony replating assay to follow the fates of individual haemopoietic progenitor cell clones. For this, human myeloid colony‐forming cells (CFCs) were cultured by standard methodology. Onset of proliferation and growth rates were established by a video recording method. Individual colonies were replated several times to document the rate of clonal extinction, and the numbers of secondary, tertiary and quaternary CFCs. The clonogenic population exhibited similar kinetics in terms of onset of proliferation and growth rate. Clonal extinction was progressive so that only 30 ± 7% (mean ± standard error of the mean; n = 4) of the original primary colonies formed quaternary colonies after the third replating step. However, individual primary CFCs that produced colonies throughout the experiment generated, on average, 40 ± 8 secondary and tertiary CFCs overall. The values obtained in standard culture conditions were modified when granulocyte colony‐stimulating factor (G‐CSF) or G‐CSF plus interleukin 3 were used to stimulate colony growth, showing that the kinetics of colony formation respond to extrinsic regulation. Examination of the replating potential of individual secondary colonies in the clones demonstrated that they generated different numbers of tertiary colonies. The data best fit a stochastic model of haemopoietic cell development where event probabilities can be modified by extracellular factors.