Puri Mira C, Bernstein Alan
Samuel Lunenfeld Research Institute, Program in Molecular Biology and Cancer, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada M5G 1X5.
Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12753-8. doi: 10.1073/pnas.2133552100. Epub 2003 Oct 6.
In mammals, the continuous production of hematopoietic cells (HCs) is sustained by a small number of hematopoietic stem cells (HSCs) residing in the bone marrow. Early HSC activity arises in the aorta-gonad mesonephros region, within cells localized to the ventral floor of the major blood vessels, suggesting that the first HSCs may be derived from cells capable of giving rise to the hematopoietic system and to the endothelial cells of the vasculature. TIE1 (TIE) and TIE2 (TEK) are related receptor tyrosine kinases with an embryonic expression pattern in endothelial cells, their precursors, and HCs, suggestive of a role in the divergence and function of both lineages. Indeed, gene targeting approaches have shown that TIE1, TIE2, and ligands for TIE2, the angiopoietins, are essential for vascular development and maintenance. To explore possible roles for these receptors in HCs, we have examined the ability of embryonic cells lacking both TIE1 and TIE2 to contribute to developmental and adult hematopoiesis by generating chimeric animals between normal embryonic cells and cells lacking these receptors. We show here that TIE receptors are not required for differentiation and proliferation of definitive hematopoietic lineages in the embryo and fetus; surprisingly, however, these receptors are specifically required during postnatal bone marrow hematopoiesis.
在哺乳动物中，少量存在于骨髓中的造血干细胞（HSC）维持着造血细胞（HC）的持续生成。早期HSC活性出现在主动脉-性腺-中肾区域，位于主要血管腹侧底部的细胞内，这表明首批HSC可能源自能够产生造血系统和脉管系统内皮细胞的细胞。TIE1（TIE）和TIE2（TEK）是相关的受体酪氨酸激酶，在内皮细胞、其前体细胞和HC中具有胚胎表达模式，提示其在这两个谱系的分化和功能中发挥作用。确实，基因靶向研究表明，TIE1、TIE2以及TIE2的配体血管生成素对于血管发育和维持至关重要。为了探究这些受体在HC中的可能作用，我们通过在正常胚胎细胞和缺乏这些受体的细胞之间生成嵌合体动物，研究了同时缺乏TIE1和TIE2的胚胎细胞参与发育中和成年造血的能力。我们在此表明，TIE受体对于胚胎和胎儿中定型造血谱系的分化和增殖并非必需；然而，令人惊讶的是，这些受体在出生后骨髓造血过程中是特异性必需的。
