ANGPTL7 regulates the expansion and repopulation of human hematopoietic stem and progenitor cells
Yiren Xiao,
Zhiwu Jiang,
Yin Li,
Wei Ye,
Bei Jia,
Minjie Zhang,
Yan Xu,
Donghai Wu,
Liangxue Lai,
Yaoyu Chen,
Yingjun Chang,
Xiaojun Huang,
Hudan Liu,
Guoliang Qing,
Pentao Liu,
Yangqiu Li,
Bing Xu,
Mei Zhong,
Yao Yao,
Duanqing Pei,
Peng Li
Affiliations
Yiren Xiao
Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, China;Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, China
Zhiwu Jiang
Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, China;Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, China
Yin Li
Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China
Wei Ye
Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, China;Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, China
Bei Jia
Department of Obstetrics and Gynecology, Nan Fang Hospital of Southern Medical University, Guangzhou, China
Minjie Zhang
Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen University Town, China;
Yan Xu
Institute of Hematology, Medical College, Jinan University, Guangzhou, China;Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, China
Donghai Wu
Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, China;Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, China
Liangxue Lai
Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, China;Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, China
Yaoyu Chen
Department of Hematology, Nanjing Medical University, China
Yingjun Chang
Peking University People’s Hospital, Peking University Institute of Hematology, Beijing, China
Xiaojun Huang
Peking University People’s Hospital, Peking University Institute of Hematology, Beijing, China
Hudan Liu
School of Pharmacy, Tongji Medical College, Huazhong Unviersity of Science and Technology, Wuhan, China
Guoliang Qing
School of Pharmacy, Tongji Medical College, Huazhong Unviersity of Science and Technology, Wuhan, China
Pentao Liu
Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK
Yangqiu Li
Institute of Hematology, Medical College, Jinan University, Guangzhou, China;Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, China
Bing Xu
Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China
Mei Zhong
Department of Obstetrics and Gynecology, Nan Fang Hospital of Southern Medical University, Guangzhou, China
Yao Yao
Drug Discovery Pipeline, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, China
Duanqing Pei
Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, China;Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, China
Peng Li
Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, China;Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, China
Successful expansion of hematopoietic stem cells would benefit the use of hematopoietic stem cell transplants in the clinic. Several angiopoietin-like proteins, including angiopoietin-like 7, can support the activity of hematopoietic stem cells. However, effects of ANGPTL7 on human hematopoietic stem cells and the downstream signaling cascade activated by ANGPTL7 are poorly understood. Here, we established a human hematopoietic stem and progenitor cell-supportive mouse fetal liver cell line that specifically expressed the Angptl7 protein. Furthermore, we found ANGPTL7 is capable of stimulating human hematopoietic stem and progenitor cell expansion and increasing the repopulation activities of human hematopoietic progenitors in xenografts. RNA-sequencing analysis showed that ANGPTL7 activated the expression of CXCR4, HOXB4 and Wnt downstream targets in human hematopoietic progenitors. In addition, chemical manipulation of Wnt signaling diminished the effects of ANGPTL7 on human hematopoietic stem and progenitor cells in culture. In summary, we identify the secreted growth factor ANGPTL7 as a regulator of both human hematopoietic stem and progenitor cell expansion and regeneration.
