Loss of Angiopoietin-like 7 diminishes the regeneration capacity of hematopoietic stem and progenitor cells.

Yiren Xiao,Xin Liu,Duanqing Pei,Bing Xu,Yao Yao,Xiangmeng Wang,Zhiwu Jiang,Xinru Wei,Huihui Yao,Pentao Liu,Peng Li,Yangqiu Li,Liangxue Lai,Minjie Zhang,Yan Xu,Donghai Wu,Zixia Liu,Su Cao,Wei Ye

doi:10.1186/s13045-014-0102-4

Abstract

Successful expansion of hematopoietic stem cells (HSCs) would benefit the use of HSC transplants in the clinic. Angiopoietin-like 7 promotes the expansion of hematopoietic stem and progenitor cells (HSPC) in vitro and ex vivo. However, the impact of loss of Angptl7 on HSPCs in vivo has not been characterized. Here, we generated Angptl7-deficient mice by TALEN-mediated gene targeting and found that HSC compartments in Angptl7-null mice were compromised. In addition, wild type (WT) HSPCs failed to repopulate in the BM of Angptl7-null mice after serial transplantations while the engraftment of Angptl7-deficient HSPCs in WT mice was not impaired. These results suggest that Angptl7 is required for HSPCs repopulation in a non-cell autonomous manner.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-014-0102-4) contains supplementary material, which is available to authorized users.

Highlights

Successful expansion of hematopoietic stem cells (HSCs) would benefit the use of HSC transplants in the clinic
We found that angiopoietin-like 7 (ANGPTL7) stimulated the proliferation of human hematopoietic stem and progenitor cells (HSPC) ex vivo (Yiren Xiao, unpublished data)
Loss of Angptl7 in Angptl7null mice was confirmed in the bone marrow (BM) by RT-PCR and Western blotting (Additional file 5: Figure S3d-3e)

Summary

Introduction

Successful expansion of hematopoietic stem cells (HSCs) would benefit the use of HSC transplants in the clinic. We generated Angptl7 knockout mice and revealed that Angptl7 is essential for HSPC repopulation in a non-cell autonomous way. To investigate whether the loss of Angptl7 affected HSPCs in vivo, we generated Angptl7-null mice by TALEN-mediated gene targeting (Additional file 1: Figure S1a-1c).

Results

Conclusion