Genetic and scRNA-seq Analysis Reveals Distinct Cell Populations that Contribute to Salivary Gland Development and Maintenance

被引:70
作者
Song, Eun-Ah Christine [1 ]
Min, Sangwon [1 ]
Oyelakin, Akinsola [1 ]
Smalley, Kirsten [2 ]
Bard, Jonathan E. [3 ]
Liao, Lan [4 ]
Xu, Jianming [4 ]
Romano, Rose-Anne [1 ,2 ]
机构
[1] SUNY Buffalo, Sch Dent Med, Dept Oral Biol, Buffalo, NY 14214 USA
[2] SUNY Buffalo, Jacobs Sch Med & Biomed Sci, Dept Biochem, Buffalo, NY 14203 USA
[3] SUNY Buffalo, Genom & Bioinformat Core, Buffalo, NY 14222 USA
[4] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA
关键词
STEM-CELLS; MYOEPITHELIAL CELLS; PROGENITOR CELLS; DELTA-NP63; EXPRESSION; BASAL; P63; MORPHOGENESIS; DYNAMICS; ACINAR;
D O I
10.1038/s41598-018-32343-z
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
Stem and progenitor cells of the submandibular salivary gland (SMG) give rise to, maintain, and regenerate the multiple lineages of mature epithelial cells including those belonging to the ductal, acinar, basal and myoepithelial subtypes. Here we have exploited single cell RNA-sequencing and in vivo genetic lineage tracing technologies to generate a detailed map of the cell fate trajectories and branch points of the basal and myoepithelial cell populations of the mouse SMG during embryonic development and in adults. Our studies show that the transcription factor p63 and alpha-smooth muscle actin (SMA) serve as faithful markers of the basal and myoepithelial cell lineages, respectively and that both cell types are endowed with progenitor cell properties. However, p63+ basal and SMA+ myoepithelial cells exhibit distinct cell fates by virtue of maintaining different cellular lineages during morphogenesis and in adults. Collectively, our results reveal the dynamic and complex nature of the diverse SMG cell populations and highlight the distinct differentiation potential of the p63 and SMA expressing subtypes in the stem and progenitor cell hierarchy. Long term these findings have profound implications towards a better understanding of the molecular mechanisms that dictate lineage commitment and differentiation programs during development and adult gland maintenance.
引用
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页数:15
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