Hematopoietic stem cells convert into liver cells within days without fusion

Nat Cell Biol. 2004 Jun;6(6):532-9. doi: 10.1038/ncb1132. Epub 2004 May 9.


Both plasticity and cell fusion have been suggested to have a role in germ-layer switching. To understand the mechanisms underlying cell fate changes, we have examined a highly enriched population of hematopoietic stem cells (HSCs) in vitro or in vivo in response to injury for liver-specific phenotypic and functional changes. Here we show that HSCs become liver cells when cocultured with injured liver separated by a barrier. Chromosomal analyses and tissue-specific gene and/or protein expression show that microenvironmental cues rather than fusion are responsible for conversion in vitro. We transplanted HSCs into liver-injured mice and observed that HSCs convert into viable hepatocytes with increasing injury. Notably, liver function was restored 2-7 d after transplantation. We conclude that HSCs contribute to the regeneration of injured liver by converting into functional hepatocytes without fusion.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biomarkers
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology*
  • Cell Lineage / genetics*
  • Cell Survival / genetics
  • Cells, Cultured
  • Coculture Techniques
  • Cues
  • Culture Media, Conditioned / pharmacology
  • Extracellular Fluid / metabolism
  • Female
  • Gene Expression Regulation, Developmental / genetics
  • Germ Layers / cytology
  • Germ Layers / metabolism*
  • Graft Survival / genetics
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / metabolism*
  • Hepatocytes / cytology
  • Hepatocytes / metabolism*
  • Liver Regeneration / genetics
  • Liver Regeneration / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Ploidies
  • Sex Chromosomes / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • Biomarkers
  • Culture Media, Conditioned
  • Transcription Factors