Transcriptional profile of LPCs and HSCs following co-culture or conditioned-medium experiments

The aim of this project was to co-culture HSCs (LX-2 cells) with wildtype or c-MET deleted LPCs (BMOL-TAT cells). Additionally, BMOL-TAT cells were indirectly co-cultured by the addition of LX-2-conditioned medium. Bulk RNA-sequencing was then performed to assess transcriptional changes during cellular crosstalk.

The results identified that LX-2 cells were not greatly affected at the transcriptional level following 48-hour co-culture with BMOL-TAT cells. However, wildtype and c-MET deleted BMOL-TAT cells were greatly affected at the transcriptomic level by signalling molecules present in LX-2-conditioned medium. This further reinforces the communicative relationship of LPCs and HSCs in diseased liver states.

Upon addition of LX-2 conditioned medium on wildtype BMOL-TAT cells, BMOL-TAT cells upregulated expression of ECM remodelling genes, while downregulating expression of ECM deposition genes and cell adhesion genes. This was contrary to c-MET deleted BMOL-TAT cells in LX-2-conditioned medium experiments, as BMOL-TAT cells without the presence of the c-MET receptor decreased expression of ECM remodelling genes, while increasing expression of ECM deposition genes and cell adhesion genes.

The data suggests that upon HSC stimulus, LPCs degrade ECM, to migrate to sites of injury and potentially aid in regeneration of the liver. However, without c-MET regulation, this process is hindered.