Publication Date:
2016-02-13
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, James Y -- Miyanishi, Masanori -- Wang, Sean K -- Yamazaki, Satoshi -- Sinha, Rahul -- Kao, Kevin S -- Seita, Jun -- Sahoo, Debashis -- Nakauchi, Hiromitsu -- Weissman, Irving L -- F30-HL122096/HL/NHLBI NIH HHS/ -- R01 CA086065/CA/NCI NIH HHS/ -- R01 HL058770/HL/NHLBI NIH HHS/ -- T32 GM007365/GM/NIGMS NIH HHS/ -- U01 HL099999/HL/NHLBI NIH HHS/ -- England -- Nature. 2016 Feb 11;530(7589):223-7. doi: 10.1038/nature16943.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA. ; Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University School of Medicine, Stanford, California 94305, USA. ; Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26863982" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antigens, CD/metabolism
;
Biomarkers/analysis
;
Bone Marrow/metabolism
;
Cadherins/metabolism
;
Cell Self Renewal
;
Gene Expression Regulation
;
Genes, Reporter/genetics
;
Hematopoietic Stem Cell Transplantation
;
Hematopoietic Stem Cells/*cytology/*metabolism
;
Homeodomain Proteins/genetics/*metabolism
;
Immunophenotyping
;
Male
;
Mice
;
Mice, Inbred C57BL
;
*Stem Cell Niche
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
