Capture of Human Neuromesodermal and Posterior Neural Tube Axial Stem Cells

Kelle, D.; Ugur, E.; Rusha, E.; Shaposhnikov, D.; Livigni, A.; Horschitz, S.; Davoudi, M.; Blutke, A.; Bushe, J.; Sterr, M.; Arkhipova, K.; Tak, B.; de Vries, R.; Hochane, M.; Spruijt, B.; Haji Ali, A.; Lickert, H.; Feuchtinger, A.; Koch, P.; Mann, M.; Leonhardt, H.; Wilson, V.; Drukker, M.

doi:10.1101/2024.03.26.586760

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bioRxiv · 10.1101/2024.03.26.586760

Capture of Human Neuromesodermal and Posterior Neural Tube Axial Stem Cells

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Abstract

The spinal cord, nerves, and skeletal muscles arise from neuromesodermal progenitors (NMPs). We have developed a growth-factor screening strategy, utilizing ES and iPS cells, facilitating the indefinite self-renewal of two types of human axial stem cells (AxSCs), closely resembling mouse NMPs (NM-AxSCs) and posterior neural tube progenitors (N-AxSCs). Under specific regimens-- Wnt/CHIR99021, FGF2, and TGF-{beta} inhibitor SB431542 (CFS) and excluding FGF2 (CS), respectively--these AxSCs self-renew and sustain telomeres. Single cell transcriptomics and proteomics have revealed expression of posterior growth-zone and dorsoventral neural tube markers in NM-AxSCs, and correspondingly, differentiation to a wide spectrum of neural tube neurons and myocytes. N-AxSCs rapidly matured into dorsal sensory subsets and neural crest. Crucially, neither AxSC type produces teratomas, and analogous mouse NM-AxSCs integrated successfully into the neural tube and somites. Capturing of AxSCs from patient and GMP ES / iPS cells without transgenesis unveils ontogeny and promises modeling and therapy in neuropathies.

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Kelle, D., Ugur, E., Rusha, E., Shaposhnikov, D., Livigni, A., Horschitz, S., Davoudi, M., Blutke, A., Bushe, J., Sterr, M., Arkhipova, K., Tak, B., de Vries, R., Hochane, M., Spruijt, B., Haji Ali, A., Lickert, H., Feuchtinger, A., Koch, P., Mann, M., Leonhardt, H., Wilson, V., Drukker, M.. 2024-03-29. Capture of Human Neuromesodermal and Posterior Neural Tube Axial Stem Cells. https://doi.org/10.1101/2024.03.26.586760

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