Journal article

Single-cell analysis of lymphatic endothelial cell fate specification and differentiation during zebrafish development

L Grimm, E Mason, H Yu, S Dudczig, V Panara, T Chen, NI Bower, S Paterson, M Rondon Galeano, S Kobayashi, A Senabouth, AK Lagendijk, J Powell, KA Smith, KS Okuda, K Koltowska, BM Hogan

EMBO Journal | Published : 2023

Open access

Abstract

During development, the lymphatic vasculature forms as a second network derived chiefly from blood vessels. The transdifferentiation of embryonic venous endothelial cells (VECs) into lymphatic endothelial cells (LECs) is a key step in this process. Specification, differentiation and maintenance of LEC fate are all driven by the transcription factor Prox1, yet the downstream mechanisms remain to be elucidated. We here present a single-cell transcriptomic atlas of lymphangiogenesis in zebrafish, revealing new markers and hallmarks of LEC differentiation over four developmental stages. We further profile single-cell transcriptomic and chromatin accessibility changes in zygotic prox1a mutants th..

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Grants

Awarded by Australian Research Council


Funding Acknowledgements

This project was supported in part by NHMRC Ideas grant 2004300 and ARC Discovery project DP180102846. BMH was supported by NHMRC Fellowship 1155221. We thank Angelika Christ and the IMB Sequence Facility (University of Queensland, UQ), Tim Semple and Peter MacCallum Cancer Centre (Peter Mac) Genomics Facility, the Research Computing Facility at Peter Mac, FACS facilities at UQ and Peter Mac, Isaac Virshup for assistance and Nathan Lawson for sharing of laboratory protocols. Imaging was conducted at the Centre for Advanced Histology and Microscopy (Peter Mac) and the Australian Cancer Research Foundation Dynamic Imaging Facility (UQ).