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A cellular hierarchy of Notch and Kras signaling controls cell fate specification in the developing mouse salivary gland

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Title
A cellular hierarchy of Notch and Kras signaling controls cell fate specification in the developing mouse salivary gland
Author(s)
Chatzeli, Lemonia; Bordeu, Ignacio; Han, Seungmin; Bisetto, Sara; Waheed, Zahra; Bonkyoung Koo; Alcolea, Maria P.; Simons, Benjamin D.
Publication Date
2023-01
Journal
DEVELOPMENTAL CELL, v.58, no.2, pp.94 - 109
Publisher
CELL PRESS
Abstract
The development of the mouse salivary gland involves a tip-driven process of branching morphogenesis that takes place in concert with differentiation into acinar, myoepithelial, and ductal (basal and luminal) sub -line-ages. By combining clonal lineage tracing with a three-dimensional (3D) reconstruction of the branched epithelial network and single-cell RNA-seq analysis, we show that in tips, a heterogeneous population of re-newing progenitors transition from a Krt14+ multipotent state to unipotent states via two transcriptionally distinct bipotent states, one restricted to the Krt14+ basal and myoepithelial lineage and the other to the Krt8+ acinar and luminal lineage. Using genetic perturbations, we show how the differential expression of Notch signaling correlates with spatial segregation, exits from multipotency, and promotes the Krt8+ lineage, whereas Kras activation promotes proacinar fate. These findings provide a mechanistic basis for how posi-tional cues within growing tips regulate the process of lineage segregation and ductal patterning.
URI
https://pr.ibs.re.kr/handle/8788114/13118
DOI
10.1016/j.devcel.2022.12.009
ISSN
1534-5807
Appears in Collections:
Center for Genome Engineering(유전체 교정 연구단) > 1. Journal Papers (저널논문)
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