iScience,Volume 27, Issue 2, 2024,109018.
Julie Warin 19, Nicolas Vedrenne 189, Vivian Tam 2, Mengxia Zhu 2, Danqing Yin 23, Xinyi Lin 23, Bluwen Guidoux-D’halluin 1, Antoine Humeau 8, Luce Roseiro 1, Lily Paillat 1, Claire Chédeville 1, Caroline Chariau 4, Frank Riemers 5, Markus Templin 6, Jérôme Guicheux 1, Marianna A. Tryfonidou 5, Joshua W.K. Ho 23, Laurent David 47, Danny Chan 2, Anne Camus 110
Summary
Understanding the emergence of human notochordal cells (NC) is essential for the development of regenerative approaches. We present a comprehensive investigation into the specification and generation of bona fide NC using a straightforward pluripotent stem cell (PSC)-based system benchmarked with human fetal notochord. By integrating in vitro and in vivo transcriptomic data at single-cell resolution, we establish an extended molecular signature and overcome the limitations associated with studying human notochordal lineage at early developmental stages. We show that TGF-β inhibition enhances the yield and homogeneity of notochordal lineage commitment in vitro. Furthermore, this study characterizes regulators of cell-fate decision and matrisome enriched in the notochordal niche. Importantly, we identify specific cell-surface markers opening avenues for differentiation refinement, NC purification, and functional studies. Altogether, this study provides a human notochord transcriptomic reference that will serve as a resource for notochord identification in human systems, diseased-tissues modeling, and facilitating future biomedical research.