Peripheral blood progenitor cell mobilisation alters myeloid, but not erythroid, progenitor cell self-renewal kinetics

Marley, Stephen B.; Lewis, John L.; Zheng, Bo; Davidson, RJ; Davis, J. G.; McDonald, Christine; Alenzi, Faris Q.; Goldman, JM; Gordon, Myrtle Y.

doi:10.1038/sj.bmt.1702777

Cited by 3 publications

(1 citation statement)

References 28 publications

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“…With a probability ε, the 2 daughter cells are exported to the downstream compartment i +1, leading to a decrease in the number of cells in compartment i to N i −1. However, with probability 1−ε, cell replication leads to identical offspring [7], [22] that remain in compartment i , such that N i increases by one (amplification) – see Figure 1.…”

Section: Methodsmentioning

confidence: 99%

Compartmental Architecture and Dynamics of Hematopoiesis

2007

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BackgroundBlood cell formation is maintained by the replication of hematopoietic stem cells (HSC) that continuously feed downstream “compartments” where amplification and differentiation of cells occurs, giving rise to all blood lineages. Whereas HSC replicate slowly, committed cells replicate faster as they become more differentiated.Methodology/Significant FindingWe propose a multi-compartment model of hematopoiesis, designed on the principle of cell flow conservation under stationary conditions. Cells lost from one compartment due to differentiation are replaced by cells from the upstream compartment. We assume that there is a constant relationship between cell input and output in each compartment and fix the single parameter of the model using data available for granulocyte maturation. We predict that ∼31 mitotic events separate the HSC from the mature cells observed in the circulation. Besides estimating the number of compartments, our model allows us to estimate the size of each compartment, the rate of cell replication within each compartment, the mean time a given cell type contributes to hematopoiesis, the amplification rate in each compartment, as well as the mean time separating stem-cell replication and mature blood-cell formation.ConclusionsDespite its simplicity, the model agrees with the limited in vivo data available and can make testable predictions. In particular, our prediction of the average lifetime of a PIG-A mutated clone agrees closely with the experimental results available for the PIG-A gene mutation in healthy adults. The present elucidation of the compartment structure and dynamics of hematopoiesis may prove insightful in further understanding a variety of hematopoietic disorders.

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Section: Methodsmentioning

confidence: 99%

Compartmental Architecture and Dynamics of Hematopoiesis

2007

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Haploinsufficiency of SNEV Causes Defects of Hematopoietic Stem Cells Functions

Schraml

Voglauer

Fortschegger

et al. 2008

Stem Cells and Development

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The quality of hematopoietic stem cells (HSCs) is essentially defined by two characteristics, i.e., multilineage differentiation and self-renewal capacity. Thus, it is of high priority to clarify mechanisms that regulate these functions and to understand them at the molecular level. In the present study, we investigated the role of senescence evasion factor (synonymously hPrp19,hPSO4,hNMP200: SNEV), a multifunctional protein involved in pre-mRNA splicing, regulation of replicative life span, and DNA repair. Here we report that murine SNEV mRNA expression is high in lineage-depleted (Lin(-)) precursor cells of the bone marrow immediately after isolation as compared to fully differentiated peripheral blood lymphocytes (PBLs). Furthermore, the progenitor cell subset with highest colony-forming ability and self-renewal capacity (Lin(-), Sca-1(+)) showed also the highest SNEV expression. To test if the observed differences in SNEV mRNA levels cause stem cell defects, Lin(-) cells derived from heterozygous SNEV knockout mice were tested for primary as well as secondary colony-forming potential as a measure of self-renewal capacity. Interestingly, both, primary and secondary colonies were significantly less formed from SNEV(+/-) cells, a defect that was rescued by ectopic SNEV expression. Similarly, bone marrow cells derived from the short-lived Senescence-Accelerated-Mouse-Prone (SAMP8) model showed similar differences in comparison to the aging-resistant (SAMR1) control strain. These data suggest that the expression of SNEV is closely associated with the growth of murine HSCs and determines the proliferative and repopulating capacity of phenotypically defined HSC subsets.

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lin– Sca-1+ Cells and Age-Dependent Changes of Their Proliferation Potential Are Reliant on Mesenchymal Stromal Cells and Are Leukemia Inhibitory Factor Dependent

et al. 2008

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Aging as a process is paralleled by a variety of hematological alterations. Characteristic features are a diminished homeostatic control of blood cell production and a decline in immune functions. It is generally accepted that stromal cells play a basal role in hematopoiesis by providing survival and differentiation signals, by secreting cytokines, or through direct contact with hematopoietic stem cells, thereby supporting the generation and replenishment of hematopoi- etic progenitor cells (HPC). Here we demonstrated that HPC-related colony formation is positively influenced by mesenchymal stromal cells (MSCs) when grown in co-culture, in particular regarding the number of primary granulocyte/macrophage colony-forming units as well as with respect to the average size of the formed colonies. These effects were more pronounced when the MSCs originated from young donors than from old ones. Because leukemia inhibitory factor (LIF) plays an important role during hematopoiesis, properties of lin– Sca-1+ cells and MSCs derived from LIF-deficient mice (LIF–/–) were determined both ex vivo and in vitro. LIF–/– animals contain a significantly reduced number of lin– Sca-1+ cells, nevertheless the replating capacity of LIF–/– HPCs was found to be generally unchanged when compared to those from LIF+/+ animals. However, when cocultured with MSCs, LIF–/– lin– Sca-1+ cells exhibited comparable characteristics to HPCs derived from old wild-type animals.

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Peripheral blood progenitor cell mobilisation alters myeloid, but not erythroid, progenitor cell self-renewal kinetics

Cited by 3 publications

References 28 publications

Compartmental Architecture and Dynamics of Hematopoiesis

Compartmental Architecture and Dynamics of Hematopoiesis

Haploinsufficiency of SNEV Causes Defects of Hematopoietic Stem Cells Functions

lin– Sca-1+ Cells and Age-Dependent Changes of Their Proliferation Potential Are Reliant on Mesenchymal Stromal Cells and Are Leukemia Inhibitory Factor Dependent

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