Publication Date:
2008-12-17
Description:
Little is known about the formation of niches, local micro-environments required for stem-cell maintenance. Here we develop an in vivo assay for adult haematopoietic stem-cell (HSC) niche formation. With this assay, we identified a population of progenitor cells with surface markers CD45(-)Tie2(-)alpha(V)(+)CD105(+)Thy1.1(-) (CD105(+)Thy1(-)) that, when sorted from 15.5 days post-coitum fetal bones and transplanted under the adult mouse kidney capsule, could recruit host-derived blood vessels, produce donor-derived ectopic bones through a cartilage intermediate and generate a marrow cavity populated by host-derived long-term reconstituting HSC (LT-HSC). In contrast, CD45(-)Tie2(-)alpha(V)(+)CD105(+)Thy1(+) (CD105(+)Thy1(+)) fetal bone progenitors form bone that does not contain a marrow cavity. Suppressing expression of factors involved in endochondral ossification, such as osterix and vascular endothelial growth factor (VEGF), inhibited niche generation. CD105(+)Thy1(-) progenitor populations derived from regions of the fetal mandible or calvaria that do not undergo endochondral ossification formed only bone without marrow in our assay. Collectively, our data implicate endochondral ossification, bone formation that proceeds through a cartilage intermediate, as a requirement for adult HSC niche formation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2648141/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2648141/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chan, Charles K F -- Chen, Ching-Cheng -- Luppen, Cynthia A -- Kim, Jae-Beom -- DeBoer, Anthony T -- Wei, Kevin -- Helms, Jill A -- Kuo, Calvin J -- Kraft, Daniel L -- Weissman, Irving L -- 1R01HL074267-01/HL/NHLBI NIH HHS/ -- 1R01NS052830-01/NS/NINDS NIH HHS/ -- 2R01HL058770-08/HL/NHLBI NIH HHS/ -- 5K99HL087936-02/HL/NHLBI NIH HHS/ -- 5R01CA086065-09/CA/NCI NIH HHS/ -- K08-HL076335/HL/NHLBI NIH HHS/ -- K99 HL087936/HL/NHLBI NIH HHS/ -- K99 HL087936-01/HL/NHLBI NIH HHS/ -- K99 HL087936-02/HL/NHLBI NIH HHS/ -- R00 HL087936/HL/NHLBI NIH HHS/ -- R00 HL087936-03/HL/NHLBI NIH HHS/ -- R00 HL087936-04/HL/NHLBI NIH HHS/ -- R00 HL087936-05/HL/NHLBI NIH HHS/ -- R01 CA086065/CA/NCI NIH HHS/ -- R01 CA086065-09/CA/NCI NIH HHS/ -- R01 HL058770/HL/NHLBI NIH HHS/ -- R01 HL058770-08/HL/NHLBI NIH HHS/ -- England -- Nature. 2009 Jan 22;457(7228):490-4. doi: 10.1038/nature07547. Epub 2008 Dec 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Developmental Biology and Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, California, USA. chazchan@stanford.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19078959" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antigens, CD/metabolism
;
Antigens, Thy-1/metabolism
;
Cartilage/*cytology/embryology
;
Choristoma
;
Fetus/cytology
;
Hematopoietic Stem Cells/*cytology/metabolism
;
Mandible/cytology/embryology
;
Mice
;
Mice, Inbred C57BL
;
Osteogenesis/*physiology
;
Skull/cytology/embryology
;
Stem Cell Niche/*cytology/*physiology
;
Transcription Factors/antagonists & inhibitors/metabolism
;
Vascular Endothelial Growth Factor A/antagonists & inhibitors/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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