Proliferation‐differentiation pathways of murine haemopoiesis: correlation of lineage fluxes

Novák, Jaroslav; Nečas, E

doi:10.1111/j.1365-2184.1994.tb01377.x

Cited by 23 publications

(19 citation statements)

References 168 publications

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“…Assuming that one femur represented 6% of the total bone marrow (12), approximately 347 million immature granulpoietic cells were present in the mouse 7 days after cy-clophosphamide, compared to 197 million in controls. The granulocytic cells thus achieved a value equivalent to the total number of bone marrow cells in untreated mouse (349 6 115 million) (13). Significant granulocytosis in blood during recovery from cyclophosphamide was also demonstrated by others (14).…”

Section: Discussionmentioning

confidence: 52%

Response of Hematopoiesis to Cyclophosphamide Follows Highly Specific Patterns in Bone Marrow and Spleen

Šefc

Psenak

Sýkora

et al. 2003

Journal of Hematotherapy & Stem Cell Research

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Sublethal cyclophosphamide treatment induces unique regeneration patterns in bone marrow and the spleen of a mouse. Colony-forming units spleen (CFU-S)(day 8), CFU-granulocyte-macrophage (GM), nucleated cell counts, and their differentials in bone marrow, spleen, and peripheral blood were determined in mice treated with a single dose of cyclophosphamide. To study further the mechanisms underlying the unique patterns of hematopoietic regeneration after cyclophosphamide, mRNA levels for stem cell factor (SCF), Flt-3 ligand, and macrophage inflammatory factor (MIP)-1 alpha cytokines were determined in bone marrow and spleen. Granulocyte precursor cells were less depleted by cyclophosphamide compared to erythroid nucleated cells and lymphocytes both in bone marrow and spleen. Rapid expansion of granulopoietic cells increased the granulocytic/erythroid ratio significantly during regeneration. CFU-S in the bone marrow and the spleen showed different sensitivity in vivo but not in vitro to cyclophosphamide; CFU-GM were equisensitive in both sites. In bone marrow, an initial fast recovery of CFU-S and CFU-GM on days 2 to 3 was followed by a secondary deep decline in their numbers occurring between days 5 and 7. This decline was accompanied with a depression of CFU-S proliferation and with significantly increased CFU-S numbers in the peripheral blood. In the spleen, absolute CFU-S and CFU-GM numbers were increased several-fold at this time. Seven days after cyclophosphamide, the spleen contained 69% of the total body CFU-S compared to 4% in controls. Splenectomy did not abolish the secondary disease of CFU-S in the bone marrow, but it led to a marked elevation of circulating leukocytes and CFU-S. There was an eight-fold increase in the SCF mRNA level in the bone marrow 2 days after cyclophosphamide, corresponding with a high proliferation rate of CFU-S. No significant changes in mRNAs for Flt-3 ligand and MIP-1 alpha have been found. This in-depth analysis of murine hematopoietic responses to cyclophosphamide provides evidence for the complexity of the involved local and systemic regulations. This represents a significant challenge to experimental hematology, which could now be tackled with methods allowing the study of changes in the gene expression during cyclophosphamide-induced hematopoietic damage.

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Section: Discussionmentioning

confidence: 52%

Response of Hematopoiesis to Cyclophosphamide Follows Highly Specific Patterns in Bone Marrow and Spleen

Šefc

Psenak

Sýkora

et al. 2003

Journal of Hematotherapy & Stem Cell Research

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“…Although raised almost two decades ago [76] this systems biology approach to stem cell dynamics must include evolutionary thinking. Approaching stem cell biology as population biology has much to offer both fields.…”

Section: Discussionmentioning

confidence: 99%

Stem cell biology is population biology: differentiation of hematopoietic multipotent progenitors to common lymphoid and myeloid progenitors

Mangel

Bonsall

2013

Theor Biol Med Model

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The hematopoietic stem cell (HSC) system is a demand control system, with the demand coming from the organism, since the products of the common myeloid and lymphoid progenitor (CMP, CLP respectively) cells are essential for activity and defense against disease. We show how ideas from population biology (combining population dynamics and evolutionary considerations) can illuminate the feedback control of the HSC system by the fully differentiated products, which has recently been verified experimentally. We develop models for the penultimate differentiation of HSC Multipotent Progenitors (MPPs) into CLP and CMP and introduce two concepts from population biology into stem cell biology. The first concept is the Multipotent Progenitor Commitment Response (MPCR) which is the probability that a multipotent progenitor cell follows a CLP route rather than a CMP route. The second concept is the link between the MPCR and a measure of Darwinian fitness associated with organismal performance and the levels of differentiated lymphoid and myeloid cells. We show that many MPCRs are consistent with homeostasis, but that they will lead to different dynamics of cells and signals following a wound or injury and thus have different consequences for Darwinian fitness. We show how coupling considerations of life history to dynamics of the HSC system and its products allows one to compute the selective pressures on cellular processes. We discuss ways that this framework can be used and extended.

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“…We can offer more insight into the nature of the replicative process between the HSC and the circulating cells in the blood. Novak & Nečas (1994) have made an extensive compilation of the available data on haematopoiesis in the mouse, and from that constructed a likely scheme for blood cell production. They estimate that the bulk of the haematopoietic production in terms of absolute numbers of cells is, as in humans, confined to granulocyte and erythrocyte production.…”

Section: Discussionmentioning

confidence: 99%

Cell kinetic status of haematopoietic stem cells

Mackey

2001

Cell Proliferation

124

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The haematopoietic stem cell (HSC) population supports a tremendous cellular production over the course of an animal's lifetime, e.g. adult humans produce their body weight in red cells, white cells and platelets every 7 years, while the mouse produces about 60% of its body weight in the course of a 2 year lifespan. Understanding how the HSC population carries this out is of interest and importance, and a first step in that understanding involves the characterization of HSC kinetics. Using previously published continuous labelling data (of Bradford et al. 1997 and Cheshier et al. 1999) from mouse HSC and a standard G0 model for the cell cycle, the steady state parameters characterizing these HSC populations are derived. It is calculated that in the mouse the differentiation rate ranges between about 0.01 and 0.02, the rate of cell re-entry from G0 back into the proliferative phase is between 0.02 and 0.05, the rate of apoptosis from the proliferative phase is between 0.07 and 0.23 (all units are days(-1)), and the duration of the proliferative phase is between 1.4 and 4.3 days. These values are compared with previously obtained values derived from the modelling by Abkowitz and colleagues of long-term haematopoietic reconstitution in the cat (Abkowitz et al. 1996) and the mouse (Abkowitz et al. 2000). It is further calculated using the estimates derived in this paper and other data on mice that between the HSC and the circulating blood cells there are between 17 and 19.5 effective cell divisions giving a net amplification of between approximately 170 000 and approximately 720 000.

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Proliferation‐differentiation pathways of murine haemopoiesis: correlation of lineage fluxes

Cited by 23 publications

References 168 publications

Response of Hematopoiesis to Cyclophosphamide Follows Highly Specific Patterns in Bone Marrow and Spleen

Response of Hematopoiesis to Cyclophosphamide Follows Highly Specific Patterns in Bone Marrow and Spleen

Stem cell biology is population biology: differentiation of hematopoietic multipotent progenitors to common lymphoid and myeloid progenitors

Cell kinetic status of haematopoietic stem cells

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