Breastmilk is a novel source of stem cells with multilineage differentiation potential.

Breastmilk is a novel source of stem cells with multilineage differentiation potential.
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DOI:
10.1002/stem.1188
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发表时间:
2012-10
期刊:
影响因子:
5.2
通讯作者:
Hartmann, Peter E.
Hartmann, Peter E.
中科院分区:
医学2区
文献类型:
--
作者:
Hassiotou, Foteini;Beltran, Adriana;Chetwynd, Ellen;Stuebe, Alison M.;Twigger, Alecia-Jane;Metzger, Philipp;Trengove, Naomi;Lai, Ching Tat;Filgueira, Luis;Blancafort, Pilar;Hartmann, Peter E.

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乳腺在妊娠和哺乳期间经历显著的重塑,这是由受控的乳腺干细胞(MaSC)增殖所推动的。人类泌乳乳腺组织标本的稀缺性以及静息乳腺中MaSC的低数量和静止状态阻碍了对正常MaSC动力学和驱动其在乳腺癌中异常自我更新的分子决定因素的理解。在这里,我们证明了人类母乳中含有具有多谱系特性的干细胞(hBSCs)。来自不同捐赠者的母乳细胞显示了通常在人类胚胎干细胞(hESC)中发现的多能性基因的可变表达。这些基因包括已知构成hESC核心自我更新回路的转录因子(TF)OCT 4、SOX 2、NANOG。当在小鼠胚胎饲养层成纤维细胞的存在下培养时,hBSC群体表现出包封的ESC样集落形态和表型,并且可以在二级和三级克隆形成培养物中传代。虽然自我更新TF被发现在正常的静息上皮中沉默,但它们在3D球体条件下培养的母乳细胞中显著上调。此外,hBSC在体外分化成来自所有三个胚层的细胞谱系。这些发现提供了证据,母乳代表了具有多系潜能的患者特异性干细胞的一种新的非侵入性来源,并建立了在培养中扩增这些细胞的方法。他们还强调了这些细胞作为新模型的潜力,以了解成体干细胞的可塑性和乳腺癌,在生物工程和组织再生的潜在用途。干细胞2012;30:2164-2174
The mammary gland undergoes significant remodeling during pregnancy and lactation, which is fuelled by controlled mammary stem cell (MaSC) proliferation. The scarcity of human lactating breast tissue specimens and the low numbers and quiescent state of MaSCs in the resting breast have hindered understanding of both normal MaSC dynamics and the molecular determinants that drive their aberrant self-renewal in breast cancer. Here, we demonstrate that human breastmilk contains stem cells (hBSCs) with multilineage properties. Breastmilk cells from different donors displayed variable expression of pluripotency genes normally found in human embryonic stem cells (hESCs). These genes included the transcription factors (TFs) OCT4, SOX2, NANOG, known to constitute the core self-renewal circuitry of hESCs. When cultured in the presence of mouse embryonic feeder fibroblasts, a population of hBSCs exhibited an encapsulated ESC-like colony morphology and phenotype and could be passaged in secondary and tertiary clonogenic cultures. While self-renewal TFs were found silenced in the normal resting epithelium, they were dramatically upregulated in breastmilk cells cultured in 3D spheroid conditions. Furthermore, hBSCs differentiated in vitro into cell lineages from all three germ layers. These findings provide evidence that breastmilk represents a novel and noninvasive source of patient-specific stem cells with multilineage potential and establish a method for expansion of these cells in culture. They also highlight the potential of these cells to be used as novel models to understand adult stem cell plasticity and breast cancer, with potential use in bioengineering and tissue regeneration. Stem Cells2012;30:2164–2174
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期刊: Breast cancer research : BCR
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发表时间: 2011-06-01
期刊: ANNALS OF SURGERY
影响因子: 9
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发表时间: 2003-05-15
影响因子: 10.5
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DOI: 10.1667/0033-7587(2001)155
发表时间: 2001-01-01
期刊: RADIATION RESEARCH
影响因子: 3.4
作者:
Chang, CC;Sun, W;Trosko, JE
通讯作者: Trosko, JE
DOI: 10.1038/onc.2011.656
发表时间: 2012-11-22
期刊: ONCOGENE
影响因子: 8
作者:
Kumar, S. M.;Liu, S.;Lu, H.;Zhang, H.;Zhang, P. J.;Gimotty, P. A.;Guerra, M.;Guo, W.;Xu, X.
通讯作者: Xu, X.