Protein in bacteria helps stem cells to be converted into neurons

Scientists have studied the issue of turning stem cells into other types of cells for a long time. Recently a study published in Chemistry & Biology on November 19 has shown some interesting findings. The study suggests that a protein in E. coli bacteria can act synergistically to push pluripotent cells into functional neurons if working together with small molecules.

In the beginning, Sungkyunkwan University scientists in Korea accidentally discovered that Sox2, one of the four Yamanaka factors that affect a stem cell's ability to remain a stem cell or differentiate, can bind to a bacterial chaperone protein, Skp. Then the researchers tested what would go on if they introduce Skp into stem cells and found that it could initiate differentiation. So they got the assumption that Skp could be combined with other techniques to make differentiation more efficient.

There have been a great amount of research in this field, but a bottleneck of producing a high number of stem cells efficiently still exists. This problem remains to be solved by looking for new ways to guide stem cell differentiation and understand the molecular mechanisms underlying improved protocols, according to co-author Kyeong Kyu Kim, of the Sungkyunkwan University School of Medicine.

The differentiation of pluripotent stem cells can be conceived as two simple steps: (1) a stem cell decides to no longer be a stem cell and begins to differentiate; (2) the cell decides what kind of cell it wants to be. The bacterial protein Skp acts in the first step by binding to Sox2 and inhibiting its function in their protocol to induce neuron differentiation. The small chemicals neurodazine (Nz) and neurodazole (Nzl) then act in the second step by telling the stem cell to become a neuron.

More functional neurons can be produced per batch of stem cells faster if using either protein or small molecules alone by influencing both steps. The synergy arises from combining suppression of stemness by protein and directing lineage-specific commitment by chemical inducers. So the process shows rationally designed cell differentiation to achieve a high level of lineage commitment efficiency.

There are also disadvantages of the protocol. For example, using bacterial proteins like Skp in a therapeutic setting may have hidden safety concerns. But comparing with introducing genetic elements, using this protein is quite advantageous, for protein cannot cause any genetic alteration or instability, thus avoiding the major concerns of using virus-mediated gene delivery to the stem cells. The authors are now calling on other researchers to develop the similar approaches to realize more possibilities.

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