title: An unexpected role for IL-3 in the embryonic development of hematopoietic stem cells.
abstract: Cytokines are important in adult hematopoiesis, yet their function in embryonic hematopoiesis has been largely unexplored. During development, hematopoietic stem cells (HSCs) are found in the aorta-gonad-mesonephros (AGM) region, yolk sac (YS), and placenta and require the Runx1 transcription factor for their normal generation. Since IL-3 is a Runx1 target and this cytokine acts on adult hematopoietic cells, we examined whether IL-3 affects HSCs in the mouse embryo. Using Runx1 haploinsufficient mice, we show that IL-3 amplifies HSCs from E11 AGM, YS, and placenta. Moreover, we show that IL-3 mutant embryos are deficient in HSCs and that IL-3 reveals the presence of HSCs in the AGM and YS prior to the stage at which HSCs are normally detected. Thus, our studies support an unexpected role for IL-3 during development and strongly suggest that IL-3 functions as a proliferation and/or survival factor for the earliest HSCs in the embryo.
authors.affiliation: Department of Cell Biology and Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Catherine
authors.initials: C
authors.lastname: Robin
authors.forename: Katrin
authors.initials: K
authors.lastname: Ottersbach
authors.forename: Charles
authors.initials: C
authors.lastname: Durand
authors.forename: Marian
authors.initials: M
authors.lastname: Peeters
authors.forename: Lesley
authors.initials: L
authors.lastname: Vanes
authors.forename: Victor
authors.initials: V
authors.lastname: Tybulewicz
authors.forename: Elaine
authors.initials: E
authors.lastname: Dzierzak
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D050676:Core Binding Factor Alpha 2 Subunit / Q000172:deficiency / Q000378:metabolism*; D047108:Embryonic Development; D006066:Gonads / Q000166:cytology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D007377:Interleukin-3 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008650:Mesonephros / Q000166:cytology; D051379:Mice; D010920:Placenta / Q000166:cytology; D015017:Yolk Sac / Q000166:cytology
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D007377:Interleukin-3; C493726:Runx1 protein, mouse