A single-cell, time-resolved profiling of Xenopus mucociliary epithelium reveals nonhierarchical model of development
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A single-cell, time-resolved profiling of Xenopus mucociliary epithelium reveals nonhierarchical model of development. / Lee, Julie; Møller, Andreas Fønss; Chae, Shinhyeok; Bussek, Alexandra; Park, Tae Joo; Kim, Youni; Lee, Hyun Shik; Pers, Tune H.; Kwon, Taejoon; Sedzinski, Jakub; Natarajan, Kedar Nath.
In: Science Advances, Vol. 9, No. 14, 2023, p. eadd5745.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - A single-cell, time-resolved profiling of Xenopus mucociliary epithelium reveals nonhierarchical model of development
AU - Lee, Julie
AU - Møller, Andreas Fønss
AU - Chae, Shinhyeok
AU - Bussek, Alexandra
AU - Park, Tae Joo
AU - Kim, Youni
AU - Lee, Hyun Shik
AU - Pers, Tune H.
AU - Kwon, Taejoon
AU - Sedzinski, Jakub
AU - Natarajan, Kedar Nath
PY - 2023
Y1 - 2023
N2 - The specialized cell types of the mucociliary epithelium (MCE) lining the respiratory tract enable continuous airway clearing, with its defects leading to chronic respiratory diseases. The molecular mechanisms driving cell fate acquisition and temporal specialization during mucociliary epithelial development remain largely unknown. Here, we profile the developing Xenopus MCE from pluripotent to mature stages by single-cell transcriptomics, identifying multipotent early epithelial progenitors that execute multilineage cues before specializing into late-stage ionocytes and goblet and basal cells. Combining in silico lineage inference, in situ hybridization, and single-cell multiplexed RNA imaging, we capture the initial bifurcation into early epithelial and multiciliated progenitors and chart cell type emergence and fate progression into specialized cell types. Comparative analysis of nine airway atlases reveals an evolutionary conserved transcriptional module in ciliated cells, whereas secretory and basal types execute distinct function-specific programs across vertebrates. We uncover a continuous nonhierarchical model of MCE development alongside a data resource for understanding respiratory biology.
AB - The specialized cell types of the mucociliary epithelium (MCE) lining the respiratory tract enable continuous airway clearing, with its defects leading to chronic respiratory diseases. The molecular mechanisms driving cell fate acquisition and temporal specialization during mucociliary epithelial development remain largely unknown. Here, we profile the developing Xenopus MCE from pluripotent to mature stages by single-cell transcriptomics, identifying multipotent early epithelial progenitors that execute multilineage cues before specializing into late-stage ionocytes and goblet and basal cells. Combining in silico lineage inference, in situ hybridization, and single-cell multiplexed RNA imaging, we capture the initial bifurcation into early epithelial and multiciliated progenitors and chart cell type emergence and fate progression into specialized cell types. Comparative analysis of nine airway atlases reveals an evolutionary conserved transcriptional module in ciliated cells, whereas secretory and basal types execute distinct function-specific programs across vertebrates. We uncover a continuous nonhierarchical model of MCE development alongside a data resource for understanding respiratory biology.
U2 - 10.1126/sciadv.add5745
DO - 10.1126/sciadv.add5745
M3 - Journal article
C2 - 37027470
AN - SCOPUS:85151990788
VL - 9
SP - eadd5745
JO - Science advances
JF - Science advances
SN - 2375-2548
IS - 14
ER -
ID: 344428422