Identification of very early lymphoid precursors in bone marrow and their regulation by estrogen

Identification of very early lymphoid precursors in bone marrow and their regulation by estrogen
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DOI:
10.1038/90659
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发表时间:
2001-08-01
期刊:
影响因子:
30.5
通讯作者:
Kincade, PW
Kincade, PW
中科院分区:
医学1区
文献类型:
--
作者:
Medina, KL;Garrett, KP;Kincade, PW

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雌激素是淋巴细胞生成的负调节因子,为探索淋巴细胞前体细胞和干细胞之间的关系提供了实验工具。我们发现淋巴细胞相关基因的表达和免疫球蛋白(IG)基因重排发生在CD 45 R获得之前。在雌激素处理的小鼠中,选择性耗尽了Lin-IL-7 R α(+)c-kit(lo)TdT(+)(谱系标志物-、白细胞介素受体7(α +)、c-kit(lo)和末端脱氧核苷酸转移酶(+))的类磷脂限制性祖细胞;在分化程度较低的Lin-c-kit(hi)部分中,B和T细胞的功能前体细胞(但不是髓样细胞)也被选择性耗尽。在该多潜能祖细胞群体的受细胞调节的Lin-c-kit(hi)Sca-I(+)CD 27(+)Flk-2(+)IL-7 R α(-)亚群中检测到TdT和IG重链转基因。这些极早期的淋巴前体细胞的鉴定应有助于研究造血中控制谱系命运决定的分子机制。
Estrogen is a negative regulator of lymphopoiesis and provides an experimental tool for probing relationships between lymphocyte precursors and stem cells. We found that expression of lymphocyte-associated genes and immunoglobulin (Ig) gene rearrangement occurred before CD45R acquisition. Lymphoid-restricted progenitors that were Lin-IL-7R alpha (+)c-kit(lo)TdT(+) (lineage marker-, interleukin receptor 7(alpha+), c-kit(lo) and terminal deoxynucleotidyl transferase(+)) were selectively depleted in estrogen-treated mice; within a less differentiated Lin-c-kit(hi) fraction, functional precursors of B and T, but not myeloid, cells were also selectively depleted. TdT and an Ig heavy chain transgene were detected within a hormone-regulated Lin-c-kit(hi)Sca-I(+)CD27(+)Flk-2(+)IL-7R alpha (-) subset of this multipotential progenitor population. Identification of these extremely early lymphoid precursors should facilitate investigation of the molecular mechanisms that control lineage-fate decisions in hematopoiesis.