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成年骨髓干细胞在H-2相容和不相容小鼠胎儿中的发育。

Development of adult bone marrow stem cells in H-2-compatible and -incompatible mouse fetuses.

作者信息

Fleischman R A, Mintz B

出版信息

J Exp Med. 1984 Mar 1;159(3):731-45. doi: 10.1084/jem.159.3.731.

DOI:10.1084/jem.159.3.731
PMID:6607968
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2187243/
Abstract

Bone marrow of normal adult mice was found, after transplacental inoculation, to contain cells still able to seed the livers of early fetuses. The recipients' own hematopoietic stem cells, with a W-mutant defect, were at a selective disadvantage. Progression of donor strain cells to the bone marrow, long-term self-renewal, and differentiation into myeloid and lymphoid derivatives was consistent with the engraftment of totipotent hematopoietic stem cells (THSC) comparable to precursors previously identified (4) in normal fetal liver. More limited stem cells, specific for the myeloid or lymphoid cell lineages, were not detected in adult bone marrow. The bone marrow THSC, however, had a generally lower capacity for self-renewal than did fetal liver THSC. They had also embarked upon irreversible changes in gene expression, including partial histocompatibility restriction. While completely allogeneic fetal liver THSC were readily accepted by fetuses, H-2 incompatibility only occasionally resulted in engraftment of adult bone marrow cells and, in these cases, was often associated with sudden death at 3-5 mo. On the other hand, H-2 compatibility, even with histocompatibility differences at other loci, was sufficient to ensure long-term success as often as with fetal liver THSC.

摘要

经胎盘接种后发现,正常成年小鼠的骨髓含有仍能在早期胎儿肝脏中定植的细胞。受体自身具有W突变缺陷的造血干细胞处于选择性劣势。供体品系细胞向骨髓的进展、长期自我更新以及分化为髓系和淋巴系衍生物,与全能造血干细胞(THSC)的植入一致,这种干细胞类似于先前在正常胎儿肝脏中鉴定出的前体细胞(4)。在成年骨髓中未检测到更有限的、特定于髓系或淋巴系细胞谱系的干细胞。然而,骨髓THSC的自我更新能力通常低于胎儿肝脏THSC。它们还开始了基因表达的不可逆变化,包括部分组织相容性限制。虽然完全异基因的胎儿肝脏THSC很容易被胎儿接受,但H-2不相容性仅偶尔导致成年骨髓细胞植入,在这些情况下,常与3至5个月时的猝死相关。另一方面,H-2相容性,即使在其他位点存在组织相容性差异,也足以像胎儿肝脏THSC一样经常确保长期成功。

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