Stem Cell Transplantation Program, Howard Hughes Medical Institute, Division of Pediatric Hematology/Oncology, Children's Hospital Boston and Dana Farber Cancer Institute, Boston, MA 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Harvard University, Boston, MA 02115, USA.
Department of Pediatric Surgery, The University of Texas Medical School at Houston, Houston, TX 77030, USA.
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.
最早的造血干细胞（HSCs）在胚胎第 11.5 天（E11.5）的主动脉-性腺-中肾（AGM）中产生，然后定植于受照射的成年小鼠中。然而，在这个阶段，用成像方法描述的 HSCs 的明显频率与其在有限稀释移植中测量的稀有程度之间存在差异。我们试图使用新生受体来协调这种差异，因为新生受体对胚胎 HSC 的定植更宽容。我们发现，来自 E9.5 和 E10.5 的胚胎 HSCs 优先定植于新生鼠，而来自 E14.5 胎肝或成年骨髓（BM）的发育成熟的、确定的 HSCs 则更有力地定植于成年鼠。用干扰素处理成年 BM 来源的 HSCs 后，可增强新生鼠的移植。成年 BM 来源的 HSCs 优先向新生鼠的肝脏归巢，但在成年鼠中向肝脏和脾脏的归巢平衡。这些发现强调了初生和成熟的确定 HSCs 之间的功能差异。
