Hoxb5 Marks Long-term Haematopoietic Stem Cells and Reveals a Homogenous Perivascular Niche

Overview

Journal Nature

Specialty Science

Date 2016 Feb 12

PMID 26863982

Citations 182

Authors

James Y Chen

Masanori Miyanishi

Sean K Wang

Satoshi Yamazaki

Rahul Sinha

Kevin S Kao

Jun Seita

Debashis Sahoo

Hiromitsu Nakauchi

Irving L Weissman

Affiliations

Soon will be listed here.

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.

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