Effect of developmental stage of HSC and recipient on transplant outcomes

Dev Cell. 2014 Jun 9;29(5):621-628. doi: 10.1016/j.devcel.2014.04.013.


The first hematopoietic stem cells (HSCs) that engraft irradiated adult mice arise in the aorta-gonad-mesonephros (AGM) on embryonic day 11.5 (E11.5). However, at this stage, there is a discrepancy between the apparent frequency of HSCs depicted with imaging and their rarity when measured with limiting dilution transplant. We have attempted to reconcile this difference using neonatal recipients, which are more permissive for embryonic HSC engraftment. We found that embryonic HSCs from E9.5 and E10.5 preferentially engrafted neonates, whereas developmentally mature, definitive HSCs from E14.5 fetal liver or adult bone marrow (BM) more robustly engrafted adults. Neonatal engraftment was enhanced after treating adult BM-derived HSCs with interferon. Adult BM-derived HSCs preferentially homed to the liver in neonatal mice yet showed balanced homing to the liver and spleen in adults. These findings emphasize the functional differences between nascent and mature definitive HSCs.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Biomarkers / metabolism
  • Bone Marrow Transplantation*
  • Cell Differentiation
  • Embryo, Mammalian / cytology*
  • Embryo, Mammalian / metabolism
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism
  • Female
  • Gene Expression Profiling
  • Gonads / cytology
  • Gonads / metabolism
  • Graft Survival / physiology*
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / metabolism
  • Liver / physiology*
  • Mesonephros / cytology
  • Mesonephros / metabolism
  • Mice
  • Oligonucleotide Array Sequence Analysis
  • Spleen / physiology*


  • Biomarkers