Fig. 5. Engrafted human hepatocytes affect rhythmic gene expression in the hypothalamus.

(A) Experimental design for SCN and ARC samples collection before RNA extraction, sequencing, and analysis according to rhythmic properties and alteration of rhythmic gene expression of murine transcript in the liver of LMM (black) and LHM (red) assessed by model selection (models 1 to 5): black line, stable transcription; black wave, rhythmic transcription; red wave, rhythmic profiles with different rhythmic parameters (i.e., phase and/or amplitude). (B to E) Heatmaps of normalized rhythmic mRNA levels (BICW > 0.5, log₂ amplitude > 0.5) and radial plot of the distribution of the peak phase of expression of the cycling genes and in the SCN (B and C) and ARC (D and E) in LMM (black) and LHM (red) from genes that lost rhythmicity in LHM (model 3). (F to I) Heatmaps of normalized rhythmic mRNA levels (BICW > 0.5, log₂ amplitude > 0.5) and radial plot of the distribution of the peak phase of expression of the cycling genes and in the SCN (F and G) and ARC (H and I) in LMM (black) and LHM (red) from genes that show altered rhythmic parameters in LHM (model 5).