Morad Vered, Pevsner-Fischer Meirav, Barnees Sivan, Samokovlisky Albena, Rousso-Noori Liat, Rosenfeld Rakefet, Zipori Dov
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Stem Cells. 2008 Sep;26(9):2275-86. doi: 10.1634/stemcells.2007-0518. Epub 2008 Jun 12.
Cultured bone marrow stromal cells create an in vitro milieu supportive of long-term hemopoiesis and serve as a source for multipotent mesenchymal progenitor cells defined by their ability to differentiate into a variety of mesodermal derivatives. This study aims to examine whether the capacity to support myelopoiesis is coupled with the multipotency. Our results show that the myelopoietic supportive ability of stromal cells, whether from the bone marrow or from embryo origin, is not linked with multipotency; cell populations that possess multipotent capacity may or may not support myelopoiesis, whereas others, lacking multipotency, may possess full myelopoietic supportive ability. However, upon differentiation, the ability of multipotent mesenchymal progenitors to support myelopoiesis is varied. Osteogenic differentiation did not affect myelopoietic supportive capacity, whereas adipogenesis resulted in reduced ability to support the maintenance of myeloid progenitor cells. These differences were accompanied by a divergence in glycosylation patterns, as measured by binding to lectin microarrays; osteogenic differentiation was associated with an increased level of antennarity of N-linked glycans, whereas adipogenic differentiation caused a decrease in antennarity. Inhibition of glycosylation prior to seeding the stroma with bone marrow cells resulted in reduced capacity of the stromal cells to support the formation of cobblestone areas. Our data show that myelopoietic support is unrelated to the multipotent phenotype of cultured mesenchymal progenitors but is dependent on the choice of differentiation pathway and upon correct glycosylation of the stromal cells.
培养的骨髓基质细胞可创造一个支持长期造血的体外环境,并作为多能间充质祖细胞的来源,这些祖细胞可通过分化为多种中胚层衍生物的能力来定义。本研究旨在探讨支持髓系造血的能力是否与多能性相关。我们的结果表明,无论是来自骨髓还是胚胎来源的基质细胞,其髓系造血支持能力与多能性无关;具有多能能力的细胞群体可能支持也可能不支持髓系造血, 而其他缺乏多能性的细胞群体可能具有完全的髓系造血支持能力。然而,在分化后,多能间充质祖细胞支持髓系造血的能力各不相同。成骨分化不影响髓系造血支持能力,而成脂分化导致支持髓系祖细胞维持的能力降低。这些差异伴随着糖基化模式的不同,通过与凝集素微阵列结合来测量;成骨分化与N-连接聚糖分支程度增加有关,而成脂分化导致分支程度降低。在用骨髓细胞接种基质细胞之前抑制糖基化,会导致基质细胞支持鹅卵石区域形成的能力降低。我们的数据表明,髓系造血支持与培养的间充质祖细胞的多能表型无关,但取决于分化途径的选择以及基质细胞的正确糖基化。