Homology model of BSEP.

<p>The amino acids affected by the E135K, R1050C, and R1153H missense mutations are represented by the red spheres. The residues affected by the L1099LfsX38 mutation are indicated by the grayed protein backbone. The two Walker motifs are highlighted with the orange backbone spheres. The transmembrane region is comprised between the two horizontal segments.</p

Patients data.

<p>Patients data.</p

(A) Liver biopsy in case 8 at 11 years of age shows preserved architecture, (HE; 10x). Liver biopsy in case 9 at 6 years of age shows (B) mild intralobular intrahepatic cholestasis (HE, 40x) and (C) fibrosis (Masson trichrome 10x); (D) IHC with anti-BSEP shows strong and diffuse staining at the canalicular edge as in control liver (not shown) (20x); (E) IHC with anti-cytokeratin 7 highlights reactive bile ductules and phenotypically modulated hepatocytes (10x).

<p>(A) Liver biopsy in case 8 at 11 years of age shows preserved architecture, (HE; 10x). Liver biopsy in case 9 at 6 years of age shows (B) mild intralobular intrahepatic cholestasis (HE, 40x) and (C) fibrosis (Masson trichrome 10x); (D) IHC with anti-BSEP shows strong and diffuse staining at the canalicular edge as in control liver (not shown) (20x); (E) IHC with anti-cytokeratin 7 highlights reactive bile ductules and phenotypically modulated hepatocytes (10x).</p

The growth capacity of the JHH-6 subpopulations CD90⁺ and CD90^-.

<p><b>A</b>. Growth curve after 12 days subculture of attached cells (<i>a</i>) and 3D colony in matrigel (<i>b</i>). <b>B</b>. mRNA analysis of cells markers (<i>a</i>), tumor promoting factors (<i>b</i>), and CSC markers genes (<i>c</i>). mRNA relative expression was normalized to reference genes 18SRNA and β-actin; the expression of CD90^- cells was considered as 1.00 (Students’ <i>t</i> test *p<0.05, ***p<0.001 compared to CD90^-). <b>C</b>. The alteration of CD90⁺ cells phenotypes during subculture. <i>Upper </i><i>panel</i>: FACS analysis of fresh-purified JHH-6 subpopulations CD90⁺ and CD90^- during subculture (passage 1-15). The number in each plots represented CD90⁺ positivity. <i>Lower </i><i>left </i><i>panel</i>: CD90 mRNA analysis of subpopulations CD90⁺ and CD90^- together with unsorted JHH-6 cells during subculture. <i>Lower </i><i>right </i><i>panel</i>: IF analysis of subpopulations CD90⁺ and CD90^-. Magnification: objective 40X.</p