Monoclonal derivation of mouse myeloid and lymphoid lineages from totipotent hematopoietic stem cells experimentally engrafted in fetal hosts.

Mintz, Beatrice; Anthony, Kate; Litwin, Samuel

doi:10.1073/pnas.81.24.7835

Cited by 93 publications

(34 citation statements)

References 19 publications

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“…Our in vitro model may mimic many features that result in assymetric division of stem cells (self-renewal coordinated with generation of differentiated progeny) and the ability of stem cells to reside for some time in Go. Indeed, normal hematopoiesis may occur through the sequential utilization of different stem cell clones (38,39). Recruitment of such clones from a "cryptic" or resting state and their subsequent differentiation program may be dependent upon the stage of cell cycle as well as sequential changes induced by CSF.…”

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 best fit for the data is a model where the adult HSC compartment consists of functionally discrete subsets of HSC, and the GOD is largely complete. Since many HSC are active at any given time point, 5,6,41,42 the steady state hematopoietic system will be derived from the combined functions of these different types of HSC. However, changes in the HSC compartment can be induced-for example through diseases, chemotherapy, transplantation, cytokine treatment, and aging.…”

Section: A Clonal Diversity Model Of the God Of Hscmentioning

confidence: 99%

The GOD of Hematopoietic Stem Cells: A Clonal Diversity Model of the Stem Cell Compartment

Müller‐Sieburg

Sieburg²

2006

Cell Cycle

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“…Previous studies have also demonstrated that the clonal contribution of individual stem cells to mature hematopoietic tissues can change with time (Mintz et al 1984;Lemischka et al 1986;Snodgrass and Keller 1987;Capel et al 1989). These fluctuations have been interpreted as a reflection of previously proposed clonal succession models of stem cell utilization (Kay 1965;Micklem et al 1983Micklem et al , 1987Mintz et al 1984}.…”

mentioning

confidence: 99%

Clonal and systemic analysis of long-term hematopoiesis in the mouse.

Jordan¹,

Lemischka²

1990

Genes Dev.

516

273

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We have analyzed the temporal in vivo fate of 142 individual stem cell clones in 63 reconstituted mice. Longterm sequential analyses of the four major peripheral blood lineages, obtained from animals engrafted with genetically marked stem cells, indicate that developmental behavior is primarily a function of time. As such, the first 4-6 months post-engraftment is characterized by frequent fluctuations in stem cell proliferation and differentiation behavior. Gradually, a stable hematopoietic system emerges, dominated by a small number of totipotent clones. We demonstrate that single stem cell clones are sufficient to maintain hematopoiesis over the lifetime of an animal and suggest that mono-or oligoclonality may be a hallmark of long-term reconstituted systems. A model is proposed, wherein lineage-restricted differentiation and dramatic clonal flux are consequences of mechanisms acting on an expanding pool of totipotent cells and are not indicative of intrinsically distinct stem cell classes.

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Monoclonal derivation of mouse myeloid and lymphoid lineages from totipotent hematopoietic stem cells experimentally engrafted in fetal hosts.

Abstract: ABSTRACT

Cited by 93 publications

References 19 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.

The GOD of Hematopoietic Stem Cells: A Clonal Diversity Model of the Stem Cell Compartment

Clonal and systemic analysis of long-term hematopoiesis in the mouse.

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