Durand Charles, Robin Catherine, Dzierzak Elaine
Department of Cell Biology and Genetics, Erasmus University Medical Center, Rotterdam, NL, the Netherlands.
Haematologica. 2006 Sep;91(9):1172-9.
The characterization of stem cell microenvironments throughout ontogeny is of fundamental interest in the field of stem cell biology. Within the adult blood system, hematopoietic stem cells (HSC) are supported in the osteoblastic and endothelial bone marrow microenvironments. During mouse mid-gestation, the first HSC emerge autonomously in the aorta-gonad-mesonephros (AGM) region. However, little is known about this microenvironment. To study the cellular complexity of the AGM hematopoietic microenvironment and its relationship to HSC, we examined the potential of AGM stromal clones to differentiate into several mesenchymal lineages.
Stromal cell clones from the mid-gestation mouse were cultured in appropriate conditions known to support osteogenic, adipogenic, chondrogenic and endothelial differentiation. Potentials of the stromal cells were scored by morphological examination of the cultures, specific staining and gene expression profile.
We show that most clones possess uni/bilineage osteogenic, adipogenic and/or endothelial potential. The differentiation potential of the stromal clones appears to relate to their site of origin but not to their ability to support hematopoiesis. Moreover, we show that AGM HSC activity is unaffected by the osteogenic differentiation of UG26.1B6 stromal cells.
These results confirm the existence of mesenchymal stem/progenitor cells in the AGM region and suggest that the AGM hematopoietic microenvironment is highly complex, containing stromal cells with various mesenchymal lineage potentials.
在个体发育过程中对干细胞微环境进行特征描述是干细胞生物学领域的一个基本研究兴趣点。在成体血液系统中,造血干细胞(HSC)在成骨细胞和内皮骨髓微环境中得到支持。在小鼠妊娠中期,首批造血干细胞在主动脉-性腺-中肾(AGM)区域自主出现。然而,关于这个微环境的了解却很少。为了研究AGM造血微环境的细胞复杂性及其与造血干细胞的关系,我们检测了AGM基质克隆分化为几种间充质谱系的潜力。
将来自妊娠中期小鼠的基质细胞克隆在已知支持成骨、成脂、成软骨和内皮分化的适当条件下培养。通过对培养物进行形态学检查、特异性染色和基因表达谱分析来评估基质细胞的潜力。
我们发现大多数克隆具有单/双谱系的成骨、成脂和/或内皮分化潜力。基质克隆的分化潜力似乎与其起源部位有关,而与其支持造血的能力无关。此外,我们还表明UG26.1B6基质细胞的成骨分化不会影响AGM造血干细胞的活性。
这些结果证实了AGM区域存在间充质干/祖细胞,并表明AGM造血微环境高度复杂,包含具有各种间充质谱系潜力的基质细胞。