NOTO, a notochord-related transcription factor, is crucial in directing human induced pluripotent stem cell-derived mesendoderm progenitors towards a notochordal fate [1]. It coordinates a gene network for human notochord differentiation, which is significant as the notochord gives rise to the nucleus pulposus, a key component for disc homeostasis [1].

The study in [1] developed a two-step method using human pluripotent stem cells. It was found that WNT pathway activation along with NOTO transfection could induce high levels of mesendoderm progenitors and bias their commitment towards the notochordal lineage instead of other mesodermal or endodermal lineages. This highlights NOTO's role in the notochord-related developmental pathway.

In conclusion, NOTO is essential for guiding the differentiation of mesendoderm progenitors into the notochordal lineage. Understanding NOTO's function can potentially contribute to the study of disc-related diseases, as it may offer insights into delaying disc degeneration or developing regenerative-cell therapies for disc repair [1].