Podocalyxin is a CD34-related marker of murine hematopoietic stem cells and embryonic erythroid cells

Podocalyxin is a CD34-related marker of murine hematopoietic stem cells and embryonic erythroid cells
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DOI:
10.1182/blood-2004-10-4077
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发表时间:
2005-06-01
期刊:
影响因子:
20.3
通讯作者:
McNagny, KM
McNagny, KM
中科院分区:
医学1区
文献类型:
--
作者:
Doyonnas, R;Nielsen, JS;McNagny, KM

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Podocalyin/Podocalyx样蛋白1[PCLP1]/血栓粘蛋白/MEP21是与CD34相关的唾液粘蛋白。我们对它在小鼠发育过程中的表达进行了详细的分析,并评估了它作为造血干细胞(HSCs)及其更分化的后代的标记的价值。我们发现,在胚胎卵黄囊形成的原始造血祖细胞和有核红细胞中,Podocalyx是高表达的。同样,Podocalyin在胎肝中由明确的多系造血祖细胞和红系前体细胞表达。随着胚胎的进一步成熟,Podocalyx的表达水平逐渐下降,在出生时达到接近本底的水平。紧随其后的是出生后的表达爆发,这与新的造血祖细胞播种到脾和骨髓有关。此后不久,Podocalyx的表达逐渐下降,到产后4周,它仅限于骨髓中罕见的SCA-1(+)、c-kit(+)、谱系标记(-)(Lin(-))细胞。这些罕见的足突蛋白表达细胞能够在致命性照射的受者体内连续重建髓系和淋巴系,表明它们具有HSC活性。综上所述,我们发现Podocalyx是胚胎HSCs和红系细胞以及成人HSCs的标志物,它可能是一种有价值的标记物,用于这些细胞的纯化和移植。
Podocalyxin/podocalyxin-like protein 1 [PCLP1]/thrombomucin/MEP21 is a CD34-related sialomucin. We have performed a detailed analysis of its expression during murine development and assessed its utility as a marker of hematopoietic stem cells (HSCs) and their more differentiated progeny. We find that podocalyxin is highly expressed by the first primitive hematopoietic progenitors and nucleated red blood cells to form in the embryonic yolk sac. Likewise, podocalyxin is expressed by definitive multilineage hematopoietic progenitors and erythroid precursors in fetal liver. The level of podocalyxin expression gradually declines with further embryo maturation and reaches near-background levels at birth. This is followed by a postnatal burst of expression that correlates with the seeding of new hematopoietic progenitors to the spleen and bone marrow. Shortly thereafter, podocalyxin expression gradually declines, and by 4 weeks postpartum it is restricted to a rare population of Sca-1 (+), c-kit(+), lineage marker(-) (Lin(-)) cells in the bone marrow. These rare podocalyxin-expressing cells are capable of serially reconstituting myeloid and lymphoid lineages in lethally irradiated recipients, suggesting they have HSC activity. in summary, we find that podocalyxin is a marker of embryonic HSCs and erythroid cells and of adult HSCs and that it may be a valuable marker for the purification of these cells for transplantation.