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Isabelle Godin

Publications and source records attributed to Isabelle Godin.

12 recordsLinked to original sources
PubMed2006

The SCL relative LYL-1 is required for fetal and adult hematopoietic stem cell function and B-cell differentiation.

Hematopoietic stem cells (HSCs) arise, self-renew, or give rise to all hematopoietic lineages through the effects of transcription factors activated by signaling cascades. Lyl-1 encodes a transcription factor containing a basic helix-hoop-helix (bHLH) motif closely related to scl/tal, which controls numerous decisions in embryonic and adult hematopoiesis. We report here that Lyl-1 null mice are viable and display normal blood cell counts, except for a reduced number of B cells resulting from a partial block after the pro-B stage. Nevertheless, the deletion of Lyl-1 results in a diminution in the frequency of immature progenitors (Lin(-), CD34(-), sca-1(+), c-kit(+) [LSK], and LSK-side population [LSK-SP]) and in S(12) colony-forming unit (CFU-S(12)) and long-term culture-initiating cell (LTC-IC) content in embryonic day 14 fetal liver (E14 FL) and adult bone marrow (BM). More important, Lyl-1(-/-) E14 FL cells and BM are severely impaired in their competitive reconstituting abilities, especially with respect to B and T lineage reconstitution. Thus, ablation of Lyl-1 quantitatively and functionally affects HSCs, a cell population that transcribes Lyl-1 more actively than their differentiated progenies. Our results demonstrate for the first time that Lyl-1 functions are important for HSC properties and B-cell differentiation and that they are largely distinct from scl functions.

Animals↗
PubMed2005

Three pathways to mature macrophages in the early mouse yolk sac.

The existence of macrophages (Mphi) of yolk-sac (YS) origin has been reported in all vertebrate models. However, the nature of their precursors and pathways of differentiation have not been elucidated. Phenotypic and differentiation potential analyses of YS at 7.5 to 10 postcoital days (dpc), performed in CX3CR1(GFP) embryos, allowed us to discern 3 independent Mphi populations. A first transient wave consisted of mature, maternal-derived Mphipresent as early as 7.5 to 8 dpc. A second wave of committed Mphi precursors arose at 8 dpc (2-4 somite stage) and was followed by a third wave of erythromyeloid precursors (4-6 somite stage). Both types of precursors displayed similar phenotypes and gave rise to CX3CR1/green fluorescent protein (GFP)-positive Mphi, but differed by their differentiation potential, at the clonal level. The combined data of phenotypic, gene-expression, and in situ analyses allowed us to conclude that the previously named "primitive Mphi" corresponded to a mixture of the first transient wave and committed Mphi precursors. Both YS-derived precursors followed a developmental pathway common to adult Mphi and could be qualified as definitive.

Animals↗
PubMed2005

A prospective study of cumulative job stress in relation to mental health.

BACKGROUND: This study tests associations between psychosocial stress at work measured by the effort-reward imbalance model in a dynamic perspective, and multiple indicators of poor mental health, in a prospective design. METHODS: 1986 male and female employees from four Belgian enterprises were followed-up over one year within the framework of the Somstress study. Based on two consecutive measurements, an index of cumulative job stress was constructed and its associations with five indicators of mental health were studied, excluding caseness at entry (for depression, anxiety, somatisation, chronic fatigue and psychotropic drug consumption respectively). Taking into account the longitudinal design, four categories of job stress are defined: 1) employees free from stress at both measures, 2) job stress present at first measure but not at the second one, 3) recent onset of job stress as evidenced by second measure 4) workers exposed to stress at both measures. Multivariate logistic regression with appropriate adjustments was applied. RESULTS: In bivariate analysis, a clear graded association of cumulative job stress with all five mental health indicators is observed, both in men and women. In multivariate logistic regression analysis, recent onset of stress is strongly associated with poor mental health among men (odds ratios ranging from 1.8 to 4.6), while cumulative stress shows strongest effects on mental health in women (odds ratios ranging from 1.4 to 7.1). CONCLUSION: Cumulative experience and recent onset of job stress in terms of high effort spent and low reward received is associated with elevated risk of all five indicators of poor mental health at follow-up in a large cohort of employees.

Achievement↗
PubMed2005

Hematopoietic stem cell development during mouse embryogenesis.

The progress of the last few years in the understanding of hematopoietic cell development during embryogenesis resulted from a combination of experimental approaches used in hematology and developmental biology. This methodology has been particularly powerful for the analysis of the earliest steps of hematopoietic ontogeny because it allows for the first time the demonstration of the existence of two independent sites of hematopoietic cell generation. Here, we describe the methods used in our laboratories to characterize the phenotype and differentiation potential of the primordial hematopoietic precursors as well as their localization in the mouse embryo. This multidisciplinary approach is required to explore the mechanisms of hematopoietic cell generation.

Animals↗
PubMed2005

Of birds and mice: hematopoietic stem cell development.

For many years it has been assumed that the ontogeny of the mammalian hematopoietic system involves sequential transfers of hematopoietic stem cells (HSCs) generated in the yolk sac blood islands, to successive hematopoietic organs as these become active in the embryo (fetal liver, thymus, spleen and eventually bone marrow). Very little was known about early events related to hematopoiesis that could take place during the 4.5 day gap separating the appearance of the yolk sac blood islands and the stage of a fully active fetal liver. Experiments performed in birds documented that the yolk sac only produce erythro-myeloid precursors that become extinct after the emergence of a second wave of intra-embryonic HSCs from the region neighbouring the dorsal aorta. The experimental approaches undertaken over the last ten years in the murine model, which are reviewed here, led to the conclusion that the rules governing avian hematopoietic development basically apply to higher vertebrates.

Animals↗
PubMed2004

Characterization of purified intraembryonic hematopoietic stem cells as a tool to define their site of origin.

Little is known about hematopoietic stem cell (HSC) development from mesoderm. To gain more information on the intraembryonic HSC site of origin, we purified multipotent hematopoietic progenitors from the aorta-gonads-mesonephros (AGM) of mice. This population, expressing c-Kit, AA4.1, CD31, and CD41, but not Flk1, and mainly negative for CD45, proved capable of long-term reconstitution in sublethally irradiated Rag2gammac(-/-) recipients. We assigned the expression of GATA-2, GATA-3, and lmo2 to AGM-HSC, whereas erythromyeloid progenitors express only GATA-2. This unique combination of surface markers and transcription factors could be allocated in the AGM to the intraaortic clusters and the subaortic patches underlying aortic endothelial cells. Taken together, those data indicate that embryonic HSCs (i) differ from their fetal liver and adult counterpart by the low expression of CD45, (ii) do not colocalize with aortic endothelial cells as previously thought, and (iii) are localized, at 10.5 days postcoitum, in the splanchnic mesoderm underlying aortic endothelial cells, within GATA-3(+)CD31(+) cell clusters.

Animals↗
PubMed2004

Differential economic stability and psychosocial stress at work: associations with psychosomatic complaints and absenteeism.

Stressful working conditions are well known to have a negative impact on the worker's health. We investigated this association in a Belgian study with a psychosocial health perspective, including individual work characteristics as well as firms' features. These data come from the first measure of the Somstress study. This is a 4 year project, initiated in 1999 and conducted in four different firms. The objective of this article is to investigate the relationships between stress, working conditions and absenteeism, self-reported health and psychosomatic complaints. Firms were selected according to their degree of structural environment and job stability. Among the four work sites, one can be considered as stable, one unstable and the remaining ones in an in-between situation. Stress is generally measured according to one of the following models: the job demands control model (Karasek) and the effort-reward imbalance model (Siegrist). We used here both models, along with the social support at work (Karasek) and overcommitment (Siegrist). Sex, age and education are important health determinants. After adjustment for those three variables and additionally for the work instability, it appeared that poor health outcomes (measured by the self-rated health, depression (SCL-90), anxiety (SCL-90), somatisation (SCL-90), chronic fatigue (Vercoulen) and reported absenteeism) are mainly associated with a low control, low social support at work, high overcommitment and high level of imbalance. Inversely, job demands do not make any significant contribution in the logistic regression models for the above-mentioned health outcomes.

Absenteeism↗
PubMed2004

The measurement of effort-reward imbalance at work: European comparisons.

Using comparative data from five countries, this study investigates the psychometric properties of the effort-reward imbalance (ERI) at work model. In this model, chronic work-related stress is identified as non-reciprocity or imbalance between high efforts spent and low rewards received. Health-adverse effects of this imbalance were documented in several prospective and cross-sectional investigations. The internal consistency, discriminant validity and factorial structure of 'effort', 'reward', and 'overcommitment' scales are evaluated, using confirmatory factor analysis. Moreover, content (or external) validity is explored with respect to a measure of self-reported health. Data for the analysis is derived from epidemiologic studies conducted in five European countries: the Somstress Study (Belgium; n = 3796), the GAZEL-Cohort Study (France; n = 10,174), the WOLF-Norrland Study (Sweden; n = 960), the Whitehall II Study (UK; n = 3697) and the Public Transport Employees Study (Germany; n = 316). Internal consistency of the scales was satisfactory in all samples, and the factorial structure of the scales was consistently confirmed (all goodness of fit measures were > 0.92). Moreover, in 12 of 14 analyses, significantly elevated odds ratios of poor health were observed in employees scoring high on the ERI scales. In conclusion, a psychometrically well-justified measure of work-related stress (ERI) grounded in sociological theory is available for comparative socioepidemiologic investigations. In the light of the importance of work for adult health such investigations are crucial in advanced societies within and beyond Europe.

Adolescent↗
PubMed2003

GATA-3 promotes maturation, IFN-gamma production, and liver-specific homing of NK cells.

The GATA-3 transcription factor has a determinant role in T cell specification and is an essential mediator of T helper 2-type polarized immune responses. While both committed NK precursors and mature NK cells express GATA-3, a role of this transcription factor in murine NK cell differentiation is not known. We found that NK cells, in contrast to T cells, can be generated in the absence of GATA-3. However, while GATA-3 antagonizes IFN-gamma production in differentiating T cells, GATA-3-deficient NK cells paradoxically produced less IFN-gamma compared to control NK cells and failed to provide early protection in vivo against infection with Listeria monocytogenes. Surprisingly, GATA-3 was essential for NK cell homing to the liver. Our results suggest that GATA-3 promotes NK cell maturation and acts in this lineage to specify distinct effector phenotypes.

Animals↗
PubMed2002

Expression of CD41 on hematopoietic progenitors derived from embryonic hematopoietic cells.

In this study, we have characterized the early steps of hematopoiesis during embryonic stem cell differentiation. The immunophenotype of hematopoietic progenitor cells derived from murine embryonic stem cells was determined using a panel of monoclonal antibodies specific for hematopoietic differentiation antigens. Surprisingly, the CD41 antigen (alphaIIb integrin, platelet GPIIb), essentially considered to be restricted to megakaryocytes, was found on a large proportion of cells within embryoid bodies although very few megakaryocytes were detected. In clonogenic assays, more than 80% of all progenitors (megakaryocytic, granulo-macrophagic, erythroid and pluripotent) derived from embryoid bodies expressed the CD41 antigen. CD41 was the most reliable marker of early steps of hematopoiesis. However, CD41 remained a differentiation marker because some CD41(-) cells from embryoid bodies converted to CD41(+) hematopoietic progenitors, whereas the inverse switch was not observed. Immunoprecipitation and western blot analysis confirmed that CD41 was present in cells from embryoid bodies associated with CD61 (beta3 integrin, platelet GPIIIa) in a complex. Analysis of CD41 expression during ontogeny revealed that most yolk sac and aorta-gonad-mesonephros hematopoietic progenitor cells were also CD41(+), whereas only a minority of bone marrow and fetal liver hematopoietic progenitors expressed this antigen. Differences in CD34 expression were also observed: hematopoietic progenitor cells from embryoid bodies, yolk sac and aorta-gonad-mesonephros displayed variable levels of CD34, whereas more than 90% of fetal liver and bone marrow progenitor cells were CD34(+). Thus, these results demonstrate that expression of CD41 is associated with early stages of hematopoiesis and is highly regulated during hematopoietic development. Further studies concerning the adhesive properties of hematopoietic cells are required to assess the biological significance of these developmental changes.

Animals↗