Ventral embryonic tissues and Hedgehog proteins induce early AGM hematopoietic stem cell development.
Hematopoiesis is initiated in several distinct tissues in the mouse conceptus. The aorta-gonad-mesonephros (AGM) region is of particular interest, as it autonomously generates the first adult type hematopoietic stem cells (HSCs). The ventral position of hematopoietic clusters closely associated with the aorta of most vertebrate embryos suggests a polarity in the specification of AGM HSCs. Since positional information plays an important role in the embryonic development of several tissue systems, we tested whether AGM HSC induction is influenced by the surrounding dorsal and ventral tissues. Our explant culture results at early and late embryonic day 10 show that ventral tissues induce and increase AGM HSC activity, whereas dorsal tissues decrease it. Chimeric explant cultures with genetically distinguishable AGM and ventral tissues show that the increase in HSC activity is not from ventral tissue-derived HSCs, precursors or primordial germ cells (as was previously suggested). Rather, it is due to instructive signaling from ventral tissues. Furthermore, we identify Hedgehog protein(s) as an HSC inducing signal.
Peeters
Marian
M
Erasmus Stem Cell Institute, Department of Cell Biology, Erasmus Medical Center, Rotterdam, The Netherlands.
Ottersbach
Katrin
K
Bollerot
Karine
K
Orelio
Claudia
C
de Bruijn
Marella
M
Wijgerde
Mark
M
Dzierzak
Elaine
E
D000818:Animals; D001011:Aorta / Q000166:cytology* / Q000378:metabolism; D002449:Cell Aggregation; D002452:Cell Count; D046528:Chimerism; D003114:Colony-Forming Units Assay; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D006066:Gonads / Q000166:cytology* / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D008650:Mesonephros / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D015398:Signal Transduction
D053823:Hedgehog Proteins