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.
journal_name
Haematologicajournal_title
Haematologicaauthors
Xiao Y,Jiang Z,Li Y,Ye W,Jia B,Zhang M,Xu Y,Wu D,Lai L,Chen Y,Chang Y,Huang X,Liu H,Qing G,Liu P,Li Y,Xu B,Zhong M,Yao Y,Pei D,Li Pdoi
10.3324/haematol.2014.118612subject
Has Abstractpub_date
2015-05-01 00:00:00pages
585-94issue
5eissn
0390-6078issn
1592-8721pii
haematol.2014.118612journal_volume
100pub_type
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