Adipose stromal cells contain phenotypically distinct adipogenic progenitors derived from neural crest.

Adipose stromal cells contain phenotypically distinct adipogenic progenitors derived from neural crest.
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DOI:
10.1371/journal.pone.0084206
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Nishino K
Nishino K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Sowa Y;Imura T;Numajiri T;Takeda K;Mabuchi Y;Matsuzaki Y;Nishino K

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最近的研究表明,脂肪来源的基质/干细胞(ASCs)包含表型和功能异质性的细胞亚群,但其发育起源和相对分化潜力仍然难以捉摸。在本研究中,我们的目的是调查如何以及在何种程度上的神经嵴有助于ASCs使用Cre-loxP介导的命运映射。从成年P0-Cre/或Wnt 1-Cre/Floxed报告基因小鼠的皮下脂肪库收获的ASC含有少量神经嵴来源的ASC(NCDASC)。该细胞亚群在标准培养条件下体外成功扩增,其生长速率与非神经嵴衍生物相当。尽管NCDASC对作为非神经嵴衍生物的几种间充质干细胞标志物呈阳性,但它们表现出独特的双极或多极形态,神经嵴祖细胞(p75 NTR、巢蛋白和Sox 2)和前脂肪细胞(CD 24、CD 34、S100、Pref-1、GATA 2和C/EBP-δ)的标志物表达更高。NCDASC能够高效分化为脂肪细胞,但其成骨和软骨形成潜力明显减弱,表明其致力于脂肪形成。在体内,一个非常小的比例的脂肪细胞起源于神经嵴。此外,p75 NTR阳性神经嵴衍生细胞被确定为沿着血管内的皮下脂肪组织,但他们是阴性的壁和内皮标志物。这些结果表明,ASC含有神经嵴衍生的脂肪细胞限制性祖细胞,其表型不同于非神经嵴衍生物。
Recent studies have shown that adipose-derived stromal/stem cells (ASCs) contain phenotypically and functionally heterogeneous subpopulations of cells, but their developmental origin and their relative differentiation potential remain elusive. In the present study, we aimed at investigating how and to what extent the neural crest contributes to ASCs using Cre-loxP-mediated fate mapping. ASCs harvested from subcutaneous fat depots of either adult P0-Cre/or Wnt1-Cre/Floxed-reporter mice contained a few neural crest-derived ASCs (NCDASCs). This subpopulation of cells was successfully expanded in vitro under standard culture conditions and their growth rate was comparable to non-neural crest derivatives. Although NCDASCs were positive for several mesenchymal stem cell markers as non-neural crest derivatives, they exhibited a unique bipolar or multipolar morphology with higher expression of markers for both neural crest progenitors (p75NTR, Nestin, and Sox2) and preadipocytes (CD24, CD34, S100, Pref-1, GATA2, and C/EBP-delta). NCDASCs were able to differentiate into adipocytes with high efficiency but their osteogenic and chondrogenic potential was markedly attenuated, indicating their commitment to adipogenesis. In vivo, a very small proportion of adipocytes were originated from the neural crest. In addition, p75NTR-positive neural crest-derived cells were identified along the vessels within the subcutaneous adipose tissue, but they were negative for mural and endothelial markers. These results demonstrate that ASCs contain neural crest-derived adipocyte-restricted progenitors whose phenotype is distinct from that of non-neural crest derivatives.
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