GENETIC REGULATION OF HUMAN FETAL LIVER AND ITS CLINICAL APPLICATION

Abstract

HUMAN LIVER PROGENITOR CELLS ARE POTENTIALLY USEFUL FOR A WIDE VARIETY OF CLINICAL APPLICATIONS. CURRENT GAPS IN UNDERSTANDING OF THE KEY MECHANISMS THAT DRIVE PROGENITOR CELLS PROLIFERATION AND MATURATION HAS LIMITED THE REALIZATION OF THEIR FULL POTENTIAL. OUR AIM IS TO DETERMINE THE KEY MESSAGE SIGNALS THAT DRIVE PROGENITOR CELL PROLIFERATION AND DIFFERENTIATION IN DEVELOPING HUMAN FETAL LIVER. HUMAN FETAL LIVER FROM 11 WEEKS TO 24 WEEKS GESTATION WAS OBTAINED WITH FULL CONSENT. USING IMMUNOPHENOTYPING AND TRANSCRIPT SIGNATURE, 5 PHASES WERE NOTED IN FETAL LIVER DEVELOPMENT. KEY GENES IN EACH PHASE CLASSIFIED UNDER TRANSCRIPTIONAL FACTORS, GROWTH FACTORS AND EXTRACELLULAR MATRIX CATEGORIES. WE DEMONSTRATED THAT COLLAGEN MATRIX MAINTAINED THE PHENOTYPIC CHARACTERISTICS OF IN VITRO. GROWTH FACTORS FGF AND CTGF WERE INVOLVED IN EXPANSION OF FETAL LIVER CELLS. THE LIVER CELLS WERE TRANSPLANTED INTO SCID MICE TREATED WITH THIOACETAMIDE DRUG AND THE DEGREE OF REPOPULATION WAS ANALYZED AND