Transcriptionally distinct mesenchymal stem/stromal cells circulate in fetus

Transcriptionally distinct mesenchymal stem/stromal cells circulate in fetus
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转录不同的间充质干细胞/基质细胞在胎儿中循环

DOI:
10.1016/j.bbrc.2019.03.033
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发表时间:
2019
影响因子:
3.1
通讯作者:
K
K
中科院分区:
生物学4区
文献类型:
--
作者:
Shimbo;T.;Endo;M.;Iwai; S.;Kitayama;T.;Ouchi;Y.;Yamamoto;R.;Takaki;E.;Yamazaki;S.;Nishida;M.;Wang;X.;Kikuchi;Y.;Tomimatsu;T.;Kaneda;Y.;Kimura;T. Tamai;K

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脐带血除了造血干细胞外,还含有间充质干细胞/基质细胞(MSCs),是一种极具吸引力的再生医学工具。由于脐带血来源于胎儿,大量的MSCs有望在胎儿体内循环。然而,胎儿循环中的MSCs的特性还没有得到充分的研究。在本研究中,我们旨在分析以血小板衍生生长因子受体α(PDGFRα)表达为标志的循环间充质干细胞在胎儿发育过程中的作用。利用PDGFRGFP基因敲除小鼠,对发育过程中循环中的αα阳性MSCs的数量进行定量。我们进一步在单细胞水平上对循环中的MSCs进行了完整的转录组分析。我们发现胚胎中有丰富的PDGFRα阳性细胞循环,出生后即刻减少。此外,单细胞RNA测序显示了胎儿循环中MSCs的转录异质性。这些数据为分析循环中MSCs在发育过程中的功能奠定了基础。
Umbilical cord blood contains mesenchymal stem/stromal cells (MSCs) in addition to hematopoietic stem cells, serving as an attractive tool for regenerative medicine. As umbilical cord blood originates from fetus, abundant MSCs are expected to circulate in fetus. However, the properties of circulating MSCs in fetus have not been fully examined. In the present study, we aimed to analyze circulating MSCs, marked by the expression of platelet-derived growth factor receptorα (PDGFRα), during fetal development. Using PDGFRα GFP knock-in mice, we quantified the number of circulating PDGFRαpositive MSCs during development. We further performed whole transcriptome analysis of circulating MSCs at single cell levels. We found that abundant PDGFRαpositive cells circulate in embryo and diminish immediately after birth. In addition, single cell RNA-sequencing revealed transcriptional heterogeneity of MSCs in fetal circulation. These data lay a foundation to analyze the function of circulating MSCs during development.