Evidence for a qualitative hierarchy within the Hoechst-33342 'side population' (SP) of murine bone marrow cells
Evidence for a qualitative hierarchy within the Hoechst-33342 'side population' (SP) of murine bone marrow cells
复制标题
DOI：
10.1038/sj.bmt.1704881
复制
发表时间：
2005-04-01
影响因子：
4.8
通讯作者：
Sharp, JG
中科院分区：
文献类型：
--
作者：
Robinson, SN;Seina, SM;Sharp, JG
体外鹅卵石区域（CA）形成细胞（CAFC）和体内（短期和竞争性再增殖）试验证明，在小鼠骨髓（BM）中Hoechst- 33342定义的侧群（SP）内存在定性层次结构。与之前的研究一致并扩展了之前的研究，我们证明（i）在整个BM（WBM）中发现的造血活性集中在SP中，而不是非SP（NSP）;和（ii）在SP中，那些更强烈地流出染料的细胞（较低的SP，LSP）与那些不太强烈流出染料的细胞（较高的SP，USP）在性质上不同。有证据表明，（i）来自LSP CAFC的CA在培养物中的持续时间明显长于来自USP CAFC的CA;（ii）LSP细胞对致死性照射小鼠的短期、多谱系再增殖比接受USP、NSP、全SP（WSP）的小鼠更快，或WBM细胞和（iii）LSP细胞在致死性照射受体的多谱系造血再增殖中胜过USP细胞。这些数据表明LSP细胞比USP细胞具有更高的质量，并潜在地提供了一种方法，通过该方法可以评估随着衰老自然发生的原始造血祖细胞的定性变化，或临床上作为治疗操作的结果。
In vitro cobblestone area ( CA)- forming cell ( CAFC) and in vivo ( short- term and competitive repopulation) assays demonstrate that a qualitative hierarchy exists within the Hoechst- 33342- defined side population ( SP) in murine bone marrow ( BM). Consistent with and extending previous studies, we demonstrate that ( i) hematopoietic activity found in whole BM ( WBM) is concentrated within the SP, rather than the non- SP ( NSP); and ( ii) within the SP, those cells that more strongly efflux the dye ( lower SP, LSP) are qualitatively different from those that less strongly efflux the dye ( upper SP, USP). Qualitative differences are highlighted by evidence that ( i) CA derived from LSP CAFC persist in culture significantly longer than CA derived from USP CAFC; ( ii) short- term, multilineage repopulation of lethally irradiated mice by LSP cells is more rapid than that in mice receiving USP, NSP, whole SP ( WSP), or WBM cells and ( iii) LSP cells out- compete USP cells in the multilineage hematopoietic repopulation of lethally irradiated recipients. These data suggest that LSP cells are of higher quality than USP cells and potentially provide a means by which qualitative changes in primitive hematopoietic progenitors occurring naturally with aging, or clinically as a consequence of therapeutic manipulation, can be assessed.