In vitro and in vivo models define a molecular signature reference for human embryonic notochordal cells

Autor: Julie Warin, Nicolas Vedrenne, Vivian Tam, Mengxia Zhu, Danqing Yin, Xinyi Lin, Bluwen Guidoux-D’halluin, Antoine Humeau, Luce Roseiro, Lily Paillat, Claire Chédeville, Caroline Chariau, Frank Riemers, Markus Templin, Jérôme Guicheux, Marianna A. Tryfonidou, Joshua W.K. Ho, Laurent David, Danny Chan, Anne Camus
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: iScience, Vol 27, Iss 2, Pp 109018- (2024)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2024.109018
Popis: 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.
Databáze: Directory of Open Access Journals