First Author | Chen JY | Year | 2016 |
Journal | Nature | Volume | 530 |
Issue | 7589 | Pages | 223-7 |
PubMed ID | 26863982 | Mgi Jnum | J:229236 |
Mgi Id | MGI:5751328 | Doi | 10.1038/nature16943 |
Citation | Chen JY, et al. (2016) Hoxb5 marks long-term haematopoietic stem cells and reveals a homogenous perivascular niche. Nature 530(7589):223-7 |
abstractText | 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. |