Identification of Flt3+ lympho-myeloid stem cells lacking erythro-megakaryocytic potential:: A revised road map for adult blood lineage commitment
Identification of Flt3+ lympho-myeloid stem cells lacking erythro-megakaryocytic potential:: A revised road map for adult blood lineage commitment
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DOI：
10.1016/j.cell.2005.02.013
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发表时间：
2005-04-22
期刊：
影响因子：
64.5
通讯作者：
Jacobsen, SEW
中科院分区：
文献类型：
--
作者：
Adolfsson, J;Månsson, R;Jacobsen, SEW
所有血细胞系均来源于共同的造血干细胞(HSC)。目前的模型暗示，成人多能造血干细胞的第一个谱系承诺步骤导致严格分离出共同的淋巴系和共同的髓系前体细胞。我们提出的证据表明，尽管保持了高度增殖和混合的淋巴-髓系分化潜能，但已经失去了采用红系和巨核系血统的能力。与Lin-SCA-1(+)cKit(+)Flt3(-)HSC相比，共表达高水平酪氨酸激酶受体Flt3的Lin-SCA-1+c-kit+HSC中的细胞维持粒细胞、单核细胞、B细胞和T细胞潜能，但不能产生明显的红系和巨核细胞后代。这个独特的谱系限制位点伴随着红系和巨核细胞发育调节基因的下调。LIN(-)SCA-L(+)c-Kit(+)CD34(+)Flt3(+)细胞表现出IL-7受体基因表达上调。基于这些观察，我们提出了修改后的成人血统发展路线图。
All blood cell lineages derive from a common hematopoietic stem cell (HSC). The current model implicates that the first lineage commitment step of adult pluripotent HSCs results in a strict separation into common lymphoid and common myeloid precursors. We present evidence for a population of cells which, although sustaining a high proliferative and combined lympho-myeloid differentiation potential, have lost the ability to adopt erythroid and megakaryocyte lineage fates. Cells in the Lin-Sca-1+c-kit+ HSC compartment coexpressing high levels of the tyrosine kinase receptor Flt3 sustain granulocyte, monocyte, and B and T cell potentials but in contrast to Lin-Sca-1(+)ckit(+)Flt3(-) HSCs fail to produce significant erythroid and megakaryocytic progeny. This distinct lineage restriction site is accompanied by downregulation of genes for regulators of erythroid and megakaryocyte development. In agreement with representing a lymphoid primed progenitor, Lin(-)Sca-l(+)c-kit(+)CD34(+)Flt3(+) cells display upregulated IL-7 receptor gene expression. Based on these observations, we propose a revised road map for adult blood lineage development.