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Open AccessArticle

NOTO Transcription Factor Directs Human Induced Pluripotent Stem Cell-Derived Mesendoderm Progenitors to a Notochordal Fate

1
INSERM UMR 1229, RMeS, Université de Nantes, ONIRIS, F-44042 Nantes, France
2
CHU Nantes, PHU 4 OTONN, F-44042 Nantes, France
3
Nantes Université, CHU Nantes, INSERM, CNRS, SFR Santé, FED 4203, Inserm UMS 016, CNRS UMS 3556, F-44042 Nantes, France
4
Nantes Université, CHU Nantes, INSERM, CRTI, UMR 1064, ITUN, F-44042 Nantes, France
5
CHU Nantes, Pharmacie Centrale, PHU 11, F-44042 Nantes, France
*
Author to whom correspondence should be addressed.
Co-senior author.
Cells 2020, 9(2), 509; https://doi.org/10.3390/cells9020509
Received: 3 January 2020 / Revised: 18 February 2020 / Accepted: 19 February 2020 / Published: 24 February 2020
The founder cells of the Nucleus pulposus, the centre of the intervertebral disc, originate in the embryonic notochord. After birth, mature notochordal cells (NC) are identified as key regulators of disc homeostasis. Better understanding of their biology has great potential in delaying the onset of disc degeneration or as a regenerative-cell source for disc repair. Using human pluripotent stem cells, we developed a two-step method to generate a stable NC-like population with a distinct molecular signature. Time-course analysis of lineage-specific markers shows that WNT pathway activation and transfection of the notochord-related transcription factor NOTO are sufficient to induce high levels of mesendoderm progenitors and favour their commitment toward the notochordal lineage instead of paraxial and lateral mesodermal or endodermal lineages. This study results in the identification of NOTO-regulated genes including some that are found expressed in human healthy disc tissue and highlights NOTO function in coordinating the gene network to human notochord differentiation. View Full-Text
Keywords: human induced pluripotent stem cells; intervertebral disc regeneration; mesendoderm progenitors; notochord; directed differentiation; signalling; stem cell therapy human induced pluripotent stem cells; intervertebral disc regeneration; mesendoderm progenitors; notochord; directed differentiation; signalling; stem cell therapy
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Colombier, P.; Halgand, B.; Chédeville, C.; Chariau, C.; François-Campion, V.; Kilens, S.; Vedrenne, N.; Clouet, J.; David, L.; Guicheux, J.; Camus, A. NOTO Transcription Factor Directs Human Induced Pluripotent Stem Cell-Derived Mesendoderm Progenitors to a Notochordal Fate. Cells 2020, 9, 509.

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