Decoding the molecular crosstalk between grafted stem cells and the stroke-injured brain

Stem cell therapy shows promise for multiple disorders; however, the molecular crosstalk between grafted cells and host tissue is largely unknown. Here, we take a step toward addressing this question. Using trans-lating ribosome affinity purification (TRAP) with sequencing tools, we simultaneously decode the transcrip-tomes of graft and host for human neural stem cells (hNSCs) transplanted into the stroke-injured rat brain. Employing pathway analysis tools, we investigate the interactions between the two transcriptomes to predict molecular pathways linking host and graft genes; as proof of concept, we predict host-secreted factors that signal to the graft and the downstream molecular cascades they trigger in the graft. We identify a potential host-graft crosstalk pathway where BMP6 from the stroke-injured brain induces graft secretion of noggin, a known brain repair factor. Decoding the molecular interplay between graft and host is a critical step toward deciphering the molecular mechanisms of stem cell action.

Automated summary

Stem cell therapy is promising for multiple disorders, but the interaction between grafted cells and host tissue is not well understood. This study used sequencing tools to decode the transcriptomes of grafted and host cells in a stroke-injured rat brain, and predicted molecular pathways linking host and graft genes. The study identified a potential host-graft crosstalk pathway where BMP6 from the stroke-injured brain induces graft secretion of noggin, a known brain repair factor.