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Inhibitory receptors bind ANGPTLs and support blood stem cells and leukaemia development.

Abstract：

:How environmental cues regulate adult stem cell and cancer cell activity through surface receptors is poorly understood. Angiopoietin-like proteins (ANGPTLs), a family of seven secreted glycoproteins, are known to support the activity of haematopoietic stem cells (HSCs) in vitro and in vivo. ANGPTLs also have important roles in lipid metabolism, angiogenesis and inflammation, but were considered 'orphan ligands' because no receptors were identified. Here we show that the immune-inhibitory receptor human leukocyte immunoglobulin-like receptor B2 (LILRB2) and its mouse orthologue paired immunoglobulin-like receptor (PIRB) are receptors for several ANGPTLs. LILRB2 and PIRB are expressed on human and mouse HSCs, respectively, and the binding of ANGPTLs to these receptors supported ex vivo expansion of HSCs. In mouse transplantation acute myeloid leukaemia models, a deficiency in intracellular signalling of PIRB resulted in increased differentiation of leukaemia cells, revealing that PIRB supports leukaemia development. Our study indicates an unexpected functional significance of classical immune-inhibitory receptors in maintenance of stemness of normal adult stem cells and in support of cancer development.

journal_name

Nature

journal_title

Nature

authors

Zheng J,Umikawa M,Cui C,Li J,Chen X,Zhang C,Huynh H,Kang X,Silvany R,Wan X,Ye J,Cantó AP,Chen SH,Wang HY,Ward ES,Zhang CC

doi

10.1038/nature11095

subject

Has Abstract

pub_date

2012-05-30 00:00:00

pages

656-60

issue

7400

eissn

0028-0836

issn

1476-4687

pii

nature11095

journal_volume

485

pub_type

杂志文章

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