A Stochastic Model of Stem Cell Proliferation, Based on the Growth of Spleen Colony-Forming Cells

Till, J. E.; McCulloch, E. A.; Siminovitch, Louis

doi:10.1073/pnas.51.1.29

Cited by 793 publications

(424 citation statements)

References 8 publications

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“…Appropriate external stimuli would act directly on stem cells to control commitment resulting in a uniform response to environmental stimuli . In contrast, the stochastic model of stem cell development predicts that multipotential stem cell differentiation is dependent upon different intrinsic probabilities that can be assigned to each of the hematopoietic lineages (32). These probabilities determine the likelihood of commitment to a specific lineage, with further commitment ofprogenitor cells being governed by progressive restriction in their differentiation potentials (33).…”

Section: Discussionmentioning

confidence: 99%

Activation and growth of colony-stimulating factor-dependent cell lines is cell cycle stage dependent.

London

McKearn

1987

The Journal of Experimental Medicine

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Hematopoietic cell development is regulated by a series of growth factors that are progressively restricted in their biological activity. IL-3 is a multi-lineage growth factor that supports the growth and differentiation of progenitor cells belonging to multiple lineages. However, the mechanism by which IL-3 induces proliferation and differentiation of these cells is not completely understood. In this report, we have used two IL-3-dependent cell lines, FDC-P1 (a myeloid progenitor) and F15.12 (a lymphoid progenitor) to investigate IL-3-mediated growth and differentiation. When either FDC-P1 or FL5.12 cells are deprived of IL-3, greater than 90% of all cells accumulate in the G0 phase of the cell cycle. Upon readdition of IL-3, the cells will reenter the active phases of the cell cycle. Therefore, IL-3 can act as both a competence (G0----G1) factor, and a progression (G1----M) factor for hematopoietic precursor clones. FDC-P1 cells can also proliferate in response to granulocyte/macrophage colony-stimulating factor (G/M-CSF) and IL-4 (B cell stimulatory factor 1 [BSF-1]). However, resting (G0) FDC-P1 cells have lost their ability to grow in response to both G/M-CSF and IL-4, even though both factors can induce a G0----G1 transition. Therefore, G/M-CSF or IL-4 behave as progression factors among certain IL-3-responsive clones, and in those cases only in defined points in the cell cycle. Both IL-4 and G/M-CSF can maintain long-term growth of FDC-P1 cells. Upon removal of factor for 24 h, these clones accumulate in the G1 phase of the cell cycle and do not appear to enter G0 even after 36 h of factor deprivation. Therefore, cells maintained in G/M-CSF or IL-4 have altered growth requirements compared with the IL-3-dependent lines from which they were derived. The ability of various hematopoietic growth factors to regulate cell cycle progression in IL-3-dependent cell lines is dependent not only upon the lineage from which these cells were derived, but also the phase of the cell cycle in which those cells reside. The consequences of these interactions dictate the manner by which various clones will respond to CSFs and whether the cells will grow and/or differentiate.

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Section: Discussionmentioning

confidence: 99%

Activation and growth of colony-stimulating factor-dependent cell lines is cell cycle stage dependent.

London

McKearn

1987

The Journal of Experimental Medicine

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“…The instructive model recognizes the role of transcription factors but proposes that cytokine signalling also plays a fundamental role in lineage determination. The stochastic hypothesis was first put forward by Till et al (1964) based on examination of the fate of colony forming units-spleen colonies in transplanted mice, and many of the early experiments predated the discovery of the current plethora of hematopoietic cytokines. The most striking in vitro evidence that cytokines can directly influence lineage choice came from studies of bipotential GM-colony forming cells (GM-CFCs).…”

Section: Cytokines: Instructive or Permissive?mentioning

confidence: 99%

Cytokine receptors and hematopoietic differentiation

2007

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“…Although the differentiation profiles of immature cells is, under certain circumstances, believed to be a stochastic process [14,15], it is possible to manipulate the system to direct these immature cells to a specific lineage. In this context, we have demonstrated at both the population and single cell level, that transduction of CD34 3ϩ CB cells, highly enriched for stem and immature subsets of myeloid progenitor cells, with an EpoR gene by retroviral-mediated gene transduction can change the differentiation profile of these immature cells with enhanced detection of numbers of erythroid cell-containing Epo-dependent colonies [7,8].…”

Section: Discussionmentioning

confidence: 99%

Transduction of recombinant human erythropoietin receptor cDNA into daughter progenitors derived from single CD343+ cord blood cells changes the differentiation profile of daughter progenitors

Lü

He³

et al. 1998

Journal of Leukocyte Biology

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A Stochastic Model of Stem Cell Proliferation, Based on the Growth of Spleen Colony-Forming Cells

Cited by 793 publications

References 8 publications

Activation and growth of colony-stimulating factor-dependent cell lines is cell cycle stage dependent.

Activation and growth of colony-stimulating factor-dependent cell lines is cell cycle stage dependent.

Cytokine receptors and hematopoietic differentiation

Transduction of recombinant human erythropoietin receptor cDNA into daughter progenitors derived from single CD343+ cord blood cells changes the differentiation profile of daughter progenitors

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