Asymmetric division and lineage commitment at the level of hematopoietic stem cells: inference from differentiation in daughter cell and granddaughter cell pairs.
Asymmetric division and lineage commitment at the level of hematopoietic stem cells: inference from differentiation in daughter cell and granddaughter cell pairs.
复制标题
DOI：
10.1084/jem.20030929
复制
发表时间：
2004-02-02
期刊：
影响因子：
--
通讯作者：
Nakauchi H
中科院分区：
文献类型：
--
作者：
Takano H;Ema H;Sudo K;Nakauchi H
造血干细胞(HSCs)如何致力于特定的谱系尚不清楚。高度的HSC纯化使我们能够在克隆水平上解决这个问题。单细胞移植研究表明，成年小鼠骨髓中40%的−/Low、c-Kit+、Sca-1+细胞和谱系标志−(CD34−KSL)细胞能够作为单个细胞长期重建髓系和B、T淋巴系。单细胞培养显示，40%的CD34KSL−细胞能形成中性粒细胞(N)/巨噬细胞(M)/红系(E)/巨核细胞(Nmem)集落。假设在这个群体中可以检测到相当一部分长期再繁殖的细胞是NMeM细胞，我们比较了单个NMeM细胞在体外获得的单个子代和孙代细胞对的分化潜力。两个子代或孙代细胞中的一个仍然是NMEM细胞。另一种表现出分化潜力的多种组合。特别是，NMeM细胞在一个细胞分裂后直接分化为致力于nm、EM或M系的祖细胞。NMEM细胞不对称分裂的概率取决于所使用的细胞因子。这些数据有力地表明，在外部因素的影响下，血统承诺在HSC水平上不对称地发生。
How hematopoietic stem cells (HSCs) commit to a particular lineage is unclear. A high degree of HSC purification enabled us to address this issue at the clonal level. Single-cell transplantation studies revealed that 40% of the CD34−/low, c-Kit+, Sca-1+, and lineage marker− (CD34−KSL) cells in adult mouse bone marrow were able, as individual cells, to reconstitute myeloid and B- and T-lymphoid lineages over the long-term. Single-cell culture showed that >40% of CD34−KSL cells could form neutrophil (n)/macrophage (m)/erythroblast (E)/megakaryocyte (M) (nmEM) colonies. Assuming that a substantial portion of long-term repopulating cells can be detected as nmEM cells within this population, we compared differentiation potentials between individual pairs of daughter and granddaughter cells derived in vitro from single nmEM cells. One of the two daughter or granddaughter cells remained an nmEM cell. The other showed a variety of combinations of differentiation potential. In particular, an nmEM cell directly gave rise, after one cell division, to progenitor cells committed to nm, EM, or M lineages. The probability of asymmetric division of nmEM cells depended on the cytokines used. These data strongly suggest that lineage commitment takes place asymmetrically at the level of HSCs under the influence of external factors.
登录
查看更多内容
影响因子：
15.3
作者：
Sudo, K;Ema, H;Morita, Y;Nakauchi, H
通讯作者：
Nakauchi, H
影响因子：
5.6
作者：
SUDA, T;SUDA, J;IHLE, JN
通讯作者：
IHLE, JN
DOI：
10.1073/pnas.81.8.2520
发表时间：
1984-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
SUDA, T;SUDA, J;OGAWA, M
通讯作者：
OGAWA, M
影响因子：
4
作者：
Cross, MA;Enver, T
通讯作者：
Enver, T
影响因子：
5.6
作者：
MAYANI, H;DRAGOWSKA, W;LANSDORP, PM
通讯作者：
LANSDORP, PM