CFU-S in individual erythroid colonies derived in vitro from adult mouse marrow

Humphries, R. Keith; Jacky, P. B.; Dill, F. J.; Eaves, Allen C.; Eaves, Connie J.

doi:10.1038/279718a0

Cited by 45 publications

(24 citation statements)

References 11 publications

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“…10,12,13,27 Later examination of clones generated in vitro from multipotent cells in the presence of soluble factors (and hence more homogeneous environments) confirmed the display of an equivalent degree of heterogeneity in the clonal outputs of multipotent cells, including progeny detectable as CFU-S. [55][56][57] The results of these later studies argue strongly against a deterministic role of external cues as the major regulators of the selfrenewal and lineage potentialities of primitive hematopoietic cells. These findings do not, however, exclude the possibility that exposure to external factors can have deterministic influences on LTRC outputs, as has been suggested.…”

Section: Hsc/ltrc Heterogeneity and The "New Reality"mentioning

confidence: 95%

Hematopoietic stem cells: concepts, definitions, and the new reality

Eaves

2015

Blood

438

315

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Hematopoietic stem cell (HSC) research took hold in the 1950s with the demonstration that intravenously injected bone marrow cells can rescue irradiated mice from lethality by reestablishing blood cell production. Attempts to quantify the cells responsible led to the discovery of serially transplantable, donor-derived, macroscopic, multilineage colonies detectable on the spleen surface 1 to 2 weeks posttransplant. The concept of self-renewing multipotent HSCs was born, but accompanied by perplexing evidence of great variability in the outcomes of HSC self-renewal divisions. The next 60 years saw an explosion in the development and use of more refined tools for assessing the behavior of prospectively purified subsets of hematopoietic cells with blood cell–producing capacity. These developments have led to the formulation of increasingly complex hierarchical models of hematopoiesis and a growing list of intrinsic and extrinsic elements that regulate HSC cycling status, viability, self-renewal, and lineage outputs. More recent examination of these properties in individual, highly purified HSCs and analyses of their perpetuation in clonally generated progeny HSCs have now provided definitive evidence of linearly transmitted heterogeneity in HSC states. These results anticipate the need and use of emerging new technologies to establish models that will accommodate such pluralistic features of HSCs and their control mechanisms.

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Section: Hsc/ltrc Heterogeneity and The "New Reality"mentioning

confidence: 95%

Hematopoietic stem cells: concepts, definitions, and the new reality

Eaves

2015

Blood

438

315

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“…Cerny (4) was the first to demonstrate that products ofactivated T lymphocytes stimulate the proliferation of pluripotent hematopoietic stem cells. His observations have been amply confirmed by both in vitro and in vivo clonal assays for stem cells with a capacity for self-renewal (5)(6)(7)(8). In addition, the in vitro proliferation of certain lineagerestricted erythroid, myeloid, and megakaryocytic progenitor cells is also supported by medium conditioned by activated T lymphocytes (9,10) but the factor or factors responsible have not been completely characterized.…”

Section: Introductionmentioning

confidence: 99%

Interleukin 3 promotes the in vitro proliferation of murine pluripotent hematopoietic stem cells.

Spivak¹,

Smith

Ihle

1985

J. Clin. Invest.

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“…The biological significance of this assay for human multipotential progenitors has been underscored by analogous developments in in vitro culture for the murine model (15)(16)(17)(18)(19). In the murine system, cultures containing pokeweed mitogen-stimulated spleen-conditioned medium are now recognized to give rise not only to pure erythroid and granulocyte-macrophage colonies, but also to large complex colonies containing varying combinations of erythroid, granulocytic, macrophage, megakaryocytic, and eosinophilic elements (15)(16)(17)19).…”

Section: Discussionmentioning

confidence: 99%

“…Studies have shown that the progenitor of at least the erythroid-megakaryocytic burst can undergo self-renewal during colony formation in vitro (17). Finally, both the ability of progenitors within individual macroscopic bursts to give rise to spleen colonies upon transfer into irradiated recipient mice (18) and the close correlation between the number of mixed colony progenitors and CFU-S in different hematopoietic tissues in the adult mouse (16) suggest that these colonyforming cells are members of the multipotential hematopoietic cell compartment with genuine stem cell properties.…”

Section: Discussionmentioning

confidence: 99%