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 translating ribosome affinity purification (TRAP) with sequencing tools, we simultaneously decode the transcriptomes 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.

Contextual fear memory retrieval by correlated ensembles of ventral CA1 neurons.

Ventral hippocampal CA1 (vCA1) projections to the amygdala are necessary for contextual fear memory. Here we used in vivo Ca2+ imaging in mice to assess the temporal dynamics by which ensembles of vCA1 neurons mediate encoding and retrieval of contextual fear memories. We found that a subset of vCA1 neurons were responsive to the aversive shock during context conditioning, their activity was necessary for memory encoding, and these shock-responsive neurons were enriched in the vCA1 projection to the amygdala. During memory retrieval, a population of vCA1 neurons became correlated with shock-encoding neurons, and the magnitude of synchronized activity within this population was proportional to memory strength. The emergence of these correlated networks was disrupted by inhibiting vCA1 shock responses during memory encoding. Thus, our findings suggest that networks of cells that become correlated with shock-responsive neurons in vCA1 are essential components of contextual fear memory ensembles.