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Project context and summary :
Erythromyeloid progenitors (EMPs) originate from the yolk sac during early mouse development and migrate to the fetal liver via the circulation where they undergo massive expansion and differentiation into hematopoietic lineages. These events occur prior to the intraembryonic emergence of hematopoietic stem cells (HSCs). Unlike HSCs, EMPs cannot give rise to lymphoid lineages, nor can they provide long-term repopulation. As such, they are considered a transient fetal population, yet it is EMP-derived hematopoiesis that supports the growth and survival of the embryo prior to the establishment of long-term hematopoitic stem cells (HSCs). Hematopoietic cell differentiation occurs along a hierarchy of progenitors with either lymphoid or myeloid fates. Common myeloid progenitors (CMPs) give rise to further restricted granulocyte-monocyte progenitors (GMPs) and megakaryocyte-erythrocyte progenitors (MEPs). This hierarchy has been well documented in adult hematopoiesis, which occurs solely from HSCs. However, fetal hematopoiesis encompasses dual origins of myeloid lineages that can originate from either EMPs or HSCs. Using genetic pulse chase labeling, we are able to distinguish these two ontologies by positively labelling EMPs and their progeny. Currently, fetal liver progenitors have been characterised by direct comparison to markers and expression profiles that are established for adult hematopoiesis. Yet, fetal hematopoietic markers may not be regulated in the same manner as their adult counterparts. Furthermore, distinguishing EMP- versus HSC-derived progeny is technically challenging and has not been properly addressed with respect to fetal liver myelopoiesis. Therefore, using our genetic pulse chase labeling approach, we would like to rebuild the differentiation tree among myeloid fetal liver progenitors. We are using high parameter flow cytometry to re-evaluate progenitor sub-populations with an expanded repertoire of markers. Since heterogeneity among progenitors (in terms of gene expression and differentiation potential) can be misrepresented and difficult to characterize on the population level, we want to investigate this on the single cell level using MARS-Seq in combination with index sorting.Related team publications :
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