In vitro and in vivo models define a molecular signature reference for human embryonic notochordal cells
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. © 2024 The Authors.
| Authors | Warin J, Vedrenne N, Tam V, Zhu M, Yin D, Lin X, Guidoux-D'halluin B, Humeau A, Roseiro L, Paillat L, Chédeville C, Chariau C, Riemers F, Templin M, Guicheux J, Tryfonidou MA, Ho JWK, David L, Chan D, Camus A |
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| Journal | iScience |
| Publication Date | 2024 Feb 16;27(2):109018 |
| PubMed | 38357665 |
| PubMed Central | PMC10865399 |
| DOI | 10.1016/j.isci.2024.109018 |