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Title: Human fetal hepatic progenitor cells are distinct from, but closely related to, hematopoietic stem/progenitor cells
Authors: Chen, Q.
Khoury, M.
Limmon, G.
Choolani, M. 
Chan, J.K.Y. 
Chen, J.
Keywords: Hematopoietic stem/progenitor cell
Hepatic progenitor cell
Humanized mouse
Liver reconstitution
Surface phenotype
Transcription profiling
Issue Date: Jun-2013
Citation: Chen, Q., Khoury, M., Limmon, G., Choolani, M., Chan, J.K.Y., Chen, J. (2013-06). Human fetal hepatic progenitor cells are distinct from, but closely related to, hematopoietic stem/progenitor cells. Stem Cells 31 (6) : 1160-1169. ScholarBank@NUS Repository.
Abstract: Much controversy surrounds the identity and origin of human hepatic stem and progenitor cells in part because of a lack of small animal models in which the developmental potential of isolated candidate cell populations can be functionally evaluated. We show here that adoptive transfer of CD34+ cells from human fetal liver into sublethally irradiated NOD-SCID Il2rg -/- (NSG) mice leads to an efficient development of not only human hematopoietic cells but also human hepatocyte-like cells in the liver of the recipient mice. Using this simple in vivo assay in combination with cell fractionation, we show that CD34+ fetal liver cells can be separated into three distinct subpopulations: CD34hiCD133hi, CD34loCD133lo, and CD34hi CD133neg. The CD34hiCD133hi population contains hematopoietic stem/progenitor cells (HSPCs) as they give rise to T cells, B cells, NK cells, dendritic cells, and monocytes/macrophages in NSG mice and colony-forming unit (CFU)-GEMM cells in vitro. The CD34loCD133lo population does not give rise to hematopoietic cells, but reproducibly generates hepatocyte-like cells in NSG mice and in vitro. The CD34hiCD133 neg population only gives rise to CFU-GM and burst-forming unit-erythroid in vitro. Furthermore, we show that the CD34 loCD133lo cells express hematopoietic, hepatic, and mesenchymal markers, including CD34, CD133, CD117, epithelial cell adhesion molecule, CD73, albumin, α-fetal protein, and vimentin and transcriptionally are more closely related to HSPCs than to mature hepatocytes. These results show that CD34loCD133lo fetal liver cells possess the hepatic progenitor cell properties and that human hepatic and hematopoietic progenitor cells are distinct, although they may originate from the same precursors in the fetal liver. © AlphaMed Press.
Source Title: Stem Cells
ISSN: 10665099
DOI: 10.1002/stem.1359
Appears in Collections:Staff Publications

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