Hoxb5 marks long-term haematopoietic stem cells and reveals a homogenous perivascular niche.
| Publication Type | Academic Article |
| Authors | Chen J, Miyanishi M, Wang S, Yamazaki S, Sinha R, Kao K, Seita J, Sahoo D, Nakauchi H, Weissman I |
| Journal | Nature |
| Volume | 530 |
| Issue | 7589 |
| Pagination | 223-7 |
| Date Published | 02/11/2016 |
| ISSN | 1476-4687 |
| Keywords | Hematopoietic Stem Cells, Homeodomain Proteins, 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 |
| PubMed ID | 26863982 |
| PubMed Central ID | PMC4854608 |