Title | Hoxb5 marks long-term haematopoietic stem cells and reveals a homogenous perivascular niche. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Chen JY, Miyanishi M, Wang SK, Yamazaki S, Sinha R, Kao KS, Seita J, Sahoo D, Nakauchi H, Weissman IL |
Journal | Nature |
Volume | 530 |
Issue | 7589 |
Pagination | 223-7 |
Date Published | 2016 Feb 11 |
ISSN | 1476-4687 |
Keywords | Animals, Antigens, CD, Biomarkers, Bone Marrow, Cadherins, Cell Self Renewal, Gene Expression Regulation, Genes, Reporter, Hematopoietic Stem Cell Transplantation, Hematopoietic Stem Cells, Homeodomain Proteins, Immunophenotyping, Male, Mice, Mice, Inbred C57BL, Stem Cell Niche |
Abstract | Haematopoietic stem cells (HSCs) are arguably the most extensively characterized tissue stem cells. Since the identification of HSCs by prospective isolation, complex multi-parameter flow cytometric isolation of phenotypic subsets has facilitated studies on many aspects of HSC biology, including self-renewal, differentiation, ageing, niche, and diversity. Here we demonstrate by unbiased multi-step screening, identification of a single gene, homeobox B5 (Hoxb5, also known as Hox-2.1), with expression in the bone marrow that is limited to long-term (LT)-HSCs in mice. Using a mouse single-colour tri-mCherry reporter driven by endogenous Hoxb5 regulation, we show that only the Hoxb5(+) HSCs exhibit long-term reconstitution capacity after transplantation in primary transplant recipients and, notably, in secondary recipients. Only 7-35% of various previously defined immunophenotypic HSCs are LT-HSCs. Finally, by in situ imaging of mouse bone marrow, we show that >94% of LT-HSCs (Hoxb5(+)) are directly attached to VE-cadherin(+) cells, implicating the perivascular space as a near-homogenous location of LT-HSCs. |
DOI | 10.1038/nature16943 |
Alternate Journal | Nature |
PubMed ID | 26863982 |
PubMed Central ID | PMC4854608 |
Grant List | T32 GM007365 / GM / NIGMS NIH HHS / United States U01 HL099999 / HL / NHLBI NIH HHS / United States R00 CA151673 / CA / NCI NIH HHS / United States F30-HL122096 / HL / NHLBI NIH HHS / United States F30 HL122096 / HL / NHLBI NIH HHS / United States R01 CA086065 / CA / NCI NIH HHS / United States R01 HL058770 / HL / NHLBI NIH HHS / United States |
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