Human fetal hepatic progenitor cells are distinct from, but closely related to, hematopoietic stem/progenitor cells

Qingfeng Chen, Maroun Khoury, Gino Limmon, Mahesh Choolani, Jerry K.Y. Chan, Jianzhu Chen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

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.

Original languageEnglish
Pages (from-to)1160-1169
Number of pages10
JournalStem Cells
Volume31
Issue number6
DOIs
StatePublished - Jun 2013
Externally publishedYes

Keywords

  • Hematopoietic stem/progenitor cell
  • Hepatic progenitor cell
  • Humanized mouse
  • Liver reconstitution
  • Surface phenotype
  • Transcription profiling

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