Defining the signalling determinants of a posterior ventral spinal cord identity in human neuromesodermal progenitor derivatives.
Matthew WindAntigoni GogolouIchcha ManipurIlaria GranataLarissa ButlerPeter W AndrewsIvana BarbaricKe NingMario R GuarracinoMarysia A PlaczekAnestis TsakiridisPublished in: Development (Cambridge, England) (2021)
The anteroposterior axial identity of motor neurons (MNs) determines their functionality and vulnerability to neurodegeneration. Thus, it is a crucial parameter in the design of strategies aiming to produce MNs from human pluripotent stem cells (hPSCs) for regenerative medicine/disease modelling applications. However, the in vitro generation of posterior MNs corresponding to the thoracic/lumbosacral spinal cord has been challenging. Although the induction of cells resembling neuromesodermal progenitors (NMPs), the bona fide precursors of the spinal cord, offers a promising solution, the progressive specification of posterior MNs from these cells is not well defined. Here, we determine the signals guiding the transition of human NMP-like cells toward thoracic ventral spinal cord neurectoderm. We show that combined WNT-FGF activities drive a posterior dorsal pre-/early neural state, whereas suppression of TGFβ-BMP signalling pathways promotes a ventral identity and neural commitment. Based on these results, we define an optimised protocol for the generation of thoracic MNs that can efficiently integrate within the neural tube of chick embryos. We expect that our findings will facilitate the comparison of hPSC-derived spinal cord cells of distinct axial identities.
Keyphrases
- spinal cord
- pluripotent stem cells
- neuropathic pain
- induced apoptosis
- spinal cord injury
- endothelial cells
- cell cycle arrest
- multiple sclerosis
- stem cells
- induced pluripotent stem cells
- endoplasmic reticulum stress
- climate change
- randomized controlled trial
- signaling pathway
- mesenchymal stem cells
- oxidative stress
- cell fate
- bone marrow