Kylie Su Mei Yong1, Choong Tat Keng1, Shu Qi Tan2, Eva Loh3, Kenneth TE Chang3,4, Thiam Chye Tan2,4, Wanjin Hong1 and Qingfeng Chen1,5,6
1 Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore.
2 Department of Obstetrics & Gynaecology, KK Women’s and Children’s Hospital, Singapore.
3 Department of Pathology and Laboratory Medicine, KK Women’s and Children’s Hospital, Singapore.
4 Duke-NUS Graduate Medical School, Singapore.
5 Interdisciplinary Research Group in Infectious Diseases, Singapore-Massachusetts Institute of Technology Alliance for Research and Technology, Singapore
6 Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Correspondence to Dr Qingfeng Chen
Published in Cellular & Molecular Immunology on 25 May 2015.
We have recently discovered a unique CD34loCD133lo cell population in the human fetal liver (FL) that gives rise to cells in the hepatic lineage. In this study, we further characterized the biological functions of FL CD34loCD133lo cells. Our findings show that these CD34loCD133lo cells express markers of both endodermal and mesodermal lineages and have the capability to differentiate into hepatocyte and mesenchymal lineage cells by ex vivo differentiation assays. Furthermore, we show that CD34loCD133lo cells express growth factors that are important for human hematopoietic stem cell (HSC) expansion: stem cell factor (SCF), insulin-like growth factor 2 (IGF2), C-X-C motif chemokine 12 (CXCL12), and factors in the angiopoietin-like protein family. Co-culture of autologous FL HSCs and allogenic HSCs derived from cord blood with CD34loCD133lo cells supports and expands both types of HSCs. These findings are not only essential for extending our understanding of the HSC niche during the development of embryonic and fetal hematopoiesis but will also potentially benefit adult stem cell transplantations in clinics because expanded HSCs demonstrate the same capacity as primary cells to reconstitute the human immune system and mediate long-term hematopoiesis in vivo. Together, CD34lo CD133lo cells not only serve as stem/progenitor cells for liver development but are also an essential component of the HSC niche in the human FL.
Figure legend: (A-D) Human fetal liver CD34loCD133lo cells have multipotent differentiation potential. CD34loCD133lo cells can give rise to (A) hepatocytes, (B) endothelial cells, (C) adipocytes, and (D) osteocytes when cultured in different conditions. (E–G) human CD34loCD133lo cells are able to support CD34hiCD133hi hematopoietic stem cell expansion in a co-culture system. (E) Representative CD34 versus CD133 staining profiles of cultured cells at day 4 and day 7 are shown. The number indicates the percentage of CD34hiCD133hi HSCs in the gated region. (F) The amount of total non-adherent cells in culture, and (G) CD34hiCD133hi HSCs in culture.
For more information on Qingfeng CHEN's laboratory, please click here.