Hematopoietic stem cells convert into liver cells within days without fusion.
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.
Jang
Yoon-Young
YY
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Collector
Michael I
MI
Baylin
Stephen B
SB
Diehl
Anna Mae
AM
Sharkis
Saul J
SJ
D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D019070:Cell Lineage / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D018920:Coculture Techniques; D003463:Cues; D017077:Culture Media, Conditioned / Q000494:pharmacology; D045604:Extracellular Fluid / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D005855:Germ Layers / Q000166:cytology / Q000378:metabolism*; D006085:Graft Survival / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D008115:Liver Regeneration / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011003:Ploidies; D012730:Sex Chromosomes / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D017077:Culture Media, Conditioned; D014157:Transcription Factors