title: Development of the fetal bone marrow niche and regulation of HSC quiescence and homing ability by emerging osteolineage cells.
abstract: Hematopoietic stem cells (HSCs) reside within a specialized niche where interactions with vasculature, osteoblasts, and stromal components regulate their self-renewal and differentiation. Little is known about bone marrow niche formation or the role of its cellular components in HSC development; therefore, we established the timing of murine fetal long bone vascularization and ossification relative to the onset of HSC activity. Adult-repopulating HSCs emerged at embryonic day 16.5 (E16.5), coincident with marrow vascularization, and were contained within the c-Kit(+)Sca-1(+)Lin(-) (KSL) population. We used Osterix-null (Osx(-/-)) mice that form vascularized marrow but lack osteolineage cells to dissect the role(s) of these cellular components in HSC development. Osx(-/-) fetal bone marrow cells formed multilineage colonies in vitro but were hyperproliferative and failed to home to and/or engraft transplant recipients. Thus, in developing bone marrow, the vasculature can sustain multilineage progenitors, but interactions with osteolineage cells are needed to regulate long-term HSC proliferation and potential.
authors.affiliation: Yale Cardiovascular Research Center, Department of Internal Medicine, Vascular Biology and Therapeutics Program and Yale Stem Cell Center, Yale University School of Medicine, 300 George Street, New Haven, CT 06511, USA; Children's Nutrition Research Center and Center for Cell and Gene Therapy, Departments of Pediatrics and Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Süleyman
authors.initials: S
authors.lastname: Coşkun
authors.affiliation: Children's Nutrition Research Center and Center for Cell and Gene Therapy, Departments of Pediatrics and Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Hsu
authors.initials: H
authors.lastname: Chao
authors.affiliation: Yale Cardiovascular Research Center, Department of Internal Medicine, Vascular Biology and Therapeutics Program and Yale Stem Cell Center, Yale University School of Medicine, 300 George Street, New Haven, CT 06511, USA.
authors.forename: Hema
authors.initials: H
authors.lastname: Vasavada
authors.affiliation: Cell Sorter Core Facility, Yale University School of Medicine, 330 Cedar Street, New Haven, CT 06511, USA.
authors.forename: Kartoosh
authors.initials: K
authors.lastname: Heydari
authors.affiliation: Children's Nutrition Research Center and Center for Cell and Gene Therapy, Departments of Pediatrics and Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Naomi
authors.initials: N
authors.lastname: Gonzales
authors.affiliation: Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Benoit
authors.initials: B
authors.lastname: de Crombrugghe
authors.affiliation: Yale Cardiovascular Research Center, Department of Internal Medicine, Vascular Biology and Therapeutics Program and Yale Stem Cell Center, Yale University School of Medicine, 300 George Street, New Haven, CT 06511, USA; Children's Nutrition Research Center and Center for Cell and Gene Therapy, Departments of Pediatrics and Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. Electronic address: karen.hirschi@yale.edu.
authors.forename: Karen K
authors.initials: KK
authors.lastname: Hirschi
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000098:blood supply / Q000196:embryology*; D019070:Cell Lineage; D049109:Cell Proliferation; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic; D010012:Osteogenesis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D000076182:Sp7 Transcription Factor; D055153:Stem Cell Niche; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors; D019009:Proto-Oncogene Proteins c-kit