An unexpected role for IL-3 in the embryonic development of hematopoietic stem cells.
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.
Robin
Catherine
C
Department of Cell Biology and Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
Ottersbach
Katrin
K
Durand
Charles
C
Peeters
Marian
M
Vanes
Lesley
L
Tybulewicz
Victor
V
Dzierzak
Elaine
E
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
D050676:Core Binding Factor Alpha 2 Subunit; D007377:Interleukin-3; C493726:Runx1 protein, mouse