title: ANGPTL7 regulates the expansion and repopulation of human hematopoietic stem and progenitor cells.
abstract: 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.
authors: 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.
authors: Yiren
authors: Y
authors: Xiao
authors: 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.
authors: Zhiwu
authors: Z
authors: Jiang
authors: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Yin
authors: Y
authors: Li
authors: 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.
authors: Wei
authors: W
authors: Ye
authors: Department of Obstetrics and Gynecology, Nan Fang Hospital of Southern Medical University, Guangzhou, China.
authors: Bei
authors: B
authors: Jia
authors: Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen University Town, China;
authors: Minjie
authors: M
authors: Zhang
authors: Institute of Hematology, Medical College, Jinan University, Guangzhou, China Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, China.
authors: Yan
authors: Y
authors: Xu
authors: 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.
authors: Donghai
authors: D
authors: Wu
authors: 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.
authors: Liangxue
authors: L
authors: Lai
authors: Department of Hematology, Nanjing Medical University, China.
authors: Yaoyu
authors: Y
authors: Chen
authors: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
authors: Yingjun
authors: Y
authors: Chang
authors: Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
authors: Xiaojun
authors: X
authors: Huang
authors: School of Pharmacy, Tongji Medical College, Huazhong Unviersity of Science and Technology, Wuhan, China.
authors: Hudan
authors: H
authors: Liu
authors: School of Pharmacy, Tongji Medical College, Huazhong Unviersity of Science and Technology, Wuhan, China.
authors: Guoliang
authors: G
authors: Qing
authors: Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
authors: Pentao
authors: P
authors: Liu
authors: Institute of Hematology, Medical College, Jinan University, Guangzhou, China Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, China.
authors: Yangqiu
authors: Y
authors: Li
authors: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Bing
authors: B
authors: Xu
authors: Department of Obstetrics and Gynecology, Nan Fang Hospital of Southern Medical University, Guangzhou, China.
authors: Mei
authors: M
authors: Zhong
authors: Drug Discovery Pipeline, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, China.
authors: Yao
authors: Y
authors: Yao
authors: 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.
authors: Duanqing
authors: D
authors: Pei
authors: 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 li_peng@gibh.ac.cn.
authors: Peng
authors: P
authors: Li
mesh_terms: D000091307:Angiopoietin-Like Protein 7; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000235:genetics* / Q000494:pharmacology; D000818:Animals; D002450:Cell Communication; D016000:Cluster Analysis; D018920:Coculture Techniques; D005312:Fetal Blood / Q000166:cytology; D015870:Gene Expression; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology; D017154:Stromal Cells / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects
chemical_list: C530622:ANGPTL7 protein, human; C000599407:ANGPTL7 protein, mouse; D000091307:Angiopoietin-Like Protein 7; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D011993:Recombinant Fusion Proteins
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