Neutral lineage tracing of proliferative embryonic and adult mammary stem/progenitor cells.

Neutral lineage tracing of proliferative embryonic and adult mammary stem/progenitor cells.
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DOI:
10.1242/dev.164079
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发表时间:
2018-07-25
期刊:
Development (Cambridge, England)
影响因子:
--
通讯作者:
Watson CJ
Watson CJ
中科院分区:
其他
文献类型:
--
作者:
Lloyd-Lewis B;Davis FM;Harris OB;Hitchcock JR;Watson CJ

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乳腺发育经历多个阶段,从哺乳动物胚胎开始一直持续到整个生殖生命。乳腺在每个发育阶段的显着形态发生能力归因于不同群体的乳腺干细胞(MaSC)和祖细胞的活动。然而,胚胎和成年 MaSC 之间的关系以及它们在乳腺形态发生的不同波中的命运仍不清楚。通过采用中性、低密度遗传标记策略,我们描述了增殖干细胞/祖细胞对胚胎、青春期和生殖乳腺发育的贡献。我们的研究结果进一步支持了出生后乳腺中 MaSC 谱系限制的模型,并强调了成体干/祖细胞池内广泛的冗余和异质性。此外,我们的数据表明,其胎儿前体存在广泛的多样性,这些前体在出生前形成了原始乳腺上皮。此外,利用单细胞标记方法,我们揭示了单个胚胎 MaSC 促进出生后导管发育的非凡能力。总之,这些发现为不同干/祖细胞对乳腺发育的不同和特定阶段的贡献提供了诱人的新见解。摘要:在胚胎、青春期和生殖乳腺发育过程中,对增殖性乳腺干细胞和祖细胞进行中性、低密度谱系追踪,揭示了不同干/祖细胞的不同和阶段特异性贡献。
Mammary gland development occurs over multiple phases, beginning in the mammalian embryo and continuing throughout reproductive life. The remarkable morphogenetic capacity of the mammary gland at each stage of development is attributed to the activities of distinct populations of mammary stem cells (MaSCs) and progenitor cells. However, the relationship between embryonic and adult MaSCs, and their fate during different waves of mammary gland morphogenesis, remains unclear. By employing a neutral, low-density genetic labelling strategy, we characterised the contribution of proliferative stem/progenitor cells to embryonic, pubertal and reproductive mammary gland development. Our findings further support a model of lineage restriction of MaSCs in the postnatal mammary gland, and highlight extensive redundancy and heterogeneity within the adult stem/progenitor cell pool. Furthermore, our data suggest extensive multiplicity in their foetal precursors that give rise to the primordial mammary epithelium before birth. In addition, using a single-cell labelling approach, we revealed the extraordinary capacity of a single embryonic MaSC to contribute to postnatal ductal development. Together, these findings provide tantalising new insights into the disparate and stage-specific contribution of distinct stem/progenitor cells to mammary gland development. Summary: Neutral, low-density lineage tracing of proliferative mammary stem and progenitor cells during embryonic, pubertal and reproductive mammary gland development reveal the disparate and stage-specific contribution of distinct stem/progenitor cells.
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