Single-cell lineage tracing in the mammary gland reveals stochastic clonal dispersion of stem/progenitor cell progeny.
Single-cell lineage tracing in the mammary gland reveals stochastic clonal dispersion of stem/progenitor cell progeny.
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DOI：
10.1038/ncomms13053
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发表时间：
2016-10-25
影响因子：
16.6
通讯作者：
Watson, Christine J.
中科院分区：
文献类型：
--
作者：
Davis, Felicity M.;Lloyd-Lewis, Bethan;Harris, Olivia B.;Kozar, Sarah;Winton, Douglas J.;Muresan, Leila;Watson, Christine J.
乳腺在整个生殖生命中经历生长和再生的周期，这一过程需要乳腺干细胞（MaSC）。虽然最近使用谱系特异性启动子的遗传命运作图研究为乳腺上皮层级提供了有价值的见解，但成人MaSCs的真正分化潜力仍不清楚。为了解决这个问题，在此我们利用随机遗传标记策略，结合组织清除和3D成像，在原位不可磨灭地标记单个细胞及其后代。使用这种方法，从单个亲本细胞产生的克隆可以整体可视化。我们发现，克隆后代的贡献完全管腔或基底谱系和零星分布的分支导管或肺泡。定量分析表明，单能干/祖细胞池有助于成年乳腺发育。我们的结果突出了追踪单个细胞的效用，并揭示了单个增殖MaSC/祖细胞的后代分散在整个上皮中。 成体乳腺干细胞的身份和起源一直备受争议。在这里，作者使用随机遗传标记方法，结合光学组织清除，来可视化克隆后代，并表明单能干/祖细胞有助于成年乳腺发育。
The mammary gland undergoes cycles of growth and regeneration throughout reproductive life, a process that requires mammary stem cells (MaSCs). Whilst recent genetic fate-mapping studies using lineage-specific promoters have provided valuable insights into the mammary epithelial hierarchy, the true differentiation potential of adult MaSCs remains unclear. To address this, herein we utilize a stochastic genetic-labelling strategy to indelibly mark a single cell and its progeny in situ, combined with tissue clearing and 3D imaging. Using this approach, clones arising from a single parent cell could be visualized in their entirety. We reveal that clonal progeny contribute exclusively to either luminal or basal lineages and are distributed sporadically to branching ducts or alveoli. Quantitative analyses suggest that pools of unipotent stem/progenitor cells contribute to adult mammary gland development. Our results highlight the utility of tracing a single cell and reveal that progeny of a single proliferative MaSC/progenitor are dispersed throughout the epithelium. The identity and origin of adult mammary stem cells has been much debated. Here, the authors use a stochastic genetic labelling approach, together with optical tissue clearing, to visualize clonal progeny and show that unipotent stem/progenitor cells contribute to adult mammary gland development.
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小鼠胚胎和产后早期乳腺发育过程中细胞角蛋白的表达
影响因子：
2.3
作者：
Sun, Peng;Yuan, Yuanyang;Dai, Xing
通讯作者：
Dai, Xing
影响因子：
4.6
作者：
Strickland, P;Shin, GC;Hinck, L
通讯作者：
Hinck, L
影响因子：
23.9
作者：
Spike BT;Engle DD;Lin JC;Cheung SK;La J;Wahl GM
通讯作者：
Wahl GM
DOI：
10.1186/bcr1371
发表时间：
2006
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Sleeman KE;Kendrick H;Ashworth A;Isacke CM;Smalley MJ
通讯作者：
Smalley MJ
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y