title: Stromal cell lines from mouse aorta-gonads-mesonephros subregions are potent supporters of hematopoietic stem cell activity.
abstract: The aorta-gonads-mesonephros (AGM) region autonomously generates the first adult repopulating hematopoietic stem cells (HSCs) in the mouse embryo. HSC activity is initially localized to the dorsal aorta and mesenchyme (AM) and vitelline and umbilical arteries. Thereafter, HSC activity is found in the urogenital ridges (UGs), yolk sac, and liver. As increasing numbers of HSCs are generated, it is thought that these sites provide supportive microenvironments in which HSCs are harbored until the bone marrow microenvironment is established. However, little is known about the supportive cells within these midgestational sites, and particularly which microenvironment is most supportive for HSC growth and maintenance. Thus, to better understand the cells and molecules involved in hematopoietic support in the midgestation embryo, more than 100 stromal cell lines and clones were established from these sites. Numerous stromal clones were found to maintain hematopoietic progenitors and HSCs to a similar degree as, or better than, previously described murine stromal lines. Both the AM and UG subregions of the AGM produced many supportive clones, with the most highly HSC-supportive clone being derived from the UGs. Interestingly, the liver at this stage yielded only few supportive stromal clones. These results strongly suggest that during midgestation, not only the AM but also the UG subregion provides a potent microenvironment for growth and maintenance of the first HSCs.
authors.affiliation: Department of Cell Biology, Erasmus University, Rotterdam, The Netherlands.
authors.forename: Robert A J
authors.initials: RA
authors.lastname: Oostendorp
authors.forename: Kirsty N
authors.initials: KN
authors.lastname: Harvey
authors.forename: Nuray
authors.initials: N
authors.lastname: Kusadasi
authors.forename: Marella F T R
authors.initials: MF
authors.lastname: de Bruijn
authors.forename: Chris
authors.initials: C
authors.lastname: Saris
authors.forename: Rob E
authors.initials: RE
authors.lastname: Ploemacher
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Medvinsky
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Dzierzak
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000196:embryology; D002450:Cell Communication; D002999:Clone Cells / Q000166:cytology; D018920:Coculture Techniques / Q000379:methods / Q000592:standards; D004064:Digestive System / Q000166:cytology* / Q000196:embryology; D006066:Gonads / Q000166:cytology / Q000196:embryology; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D008099:Liver / Q000166:cytology / Q000196:embryology; D008650:Mesonephros / Q000166:cytology / Q000196:embryology; D051379:Mice; D008822:Mice, Transgenic; D017154:Stromal Cells / Q000166:cytology*