Effect of developmental stage of HSC and recipient on transplant outcomes.

Effect of developmental stage of HSC and recipient on transplant outcomes.
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DOI:
10.1016/j.devcel.2014.04.013
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发表时间:
2014-06-09
期刊:
影响因子:
11.8
通讯作者:
Daley, George Q.
Daley, George Q.
中科院分区:
生物学1区
文献类型:
--
作者:
Arora, Natasha;Wenzel, Pamela L.;McKinney-Freeman, Shannon L.;Ross, Samantha J.;Kim, Peter G.;Chou, Stephanie S.;Yoshimoto, Momoko;Yoder, Mervin C.;Daley, George Q.

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第一个造血干细胞(HSC)植入照射后的成年小鼠产生于胚胎第11.5天(E11.5)的中肾(AGM)。然而,在这个阶段,有一个显着的频率之间的差异,通过成像和有限稀释移植测量时,它们的稀有性建议HSC。我们试图用新生儿受体来调和这一差异,新生儿受体对胚胎HSC植入更宽容。我们发现E9.5和E10.5的胚胎HSC优先移植新生儿,而E14.5胎肝(FL)或成人骨髓(BM)的发育成熟的永久性HSC更稳健地移植成人。用干扰素处理成人骨髓来源的造血干细胞后,新生儿植入增强。成年骨髓来源的造血干细胞优先归巢到新生小鼠的肝脏,但在成年小鼠中表现出平衡的肝脏和脾脏归巢。这些发现强调了新生和成熟的永久性HSC之间的功能差异。
The first hematopoietic stem cells (HSCs) that engraft irradiated adult mice arise in the aortagonad-mesonephros (AGM) on embryonic day 11.5 (E11.5). However, at this stage there is a discrepancy between the apparent frequency of HSCs suggested by imaging and their rarity when measured by 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 (FL) 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.
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