PMID- 15005571
OWN - NLM
STAT- MEDLINE
DCOM- 20040924
LR  - 20191108
IS  - 0214-6282 (Print)
IS  - 0214-6282 (Linking)
VI  - 48
IP  - 1
DP  - 2004 Feb
TI  - Quantitative gene expression profiling reveals a fetal hepatic phenotype of 
      murine ES-derived hepatocytes.
PG  - 23-9
AB  - To use embryonic stem (ES) cells in future therapeutical applications, 
      differentiated hepatic phenotypes with specific liver functions would be 
      necessary. We analyzed albumin (ALB), alpha-fetoprotein (AFP) and hepatic 
      transcription factor (TF) gene expression in tissues derived from embryonic, 
      fetal and adult liver, and compared the gene expression profiles with those from 
      mouse ES cells after hepatic differentiation and from cultured adult hepatocytes. 
      The mRNA expression of hepatocyte nuclear factor (HNF)-1alpha,beta, -3alpha,beta, 
      -4alpha, -6, CCAAT/enhancer binding protein (C/EBP) alpha,beta, ALB and AFP 
      relative to glyceralaldehyde-3-phosphate dehydrogenase (GAPDH) were studied by 
      "real time" RT-PCR. ALBand AFP-expression was also determined by in situ 
      hybridization (tissue) and immunofluorescence (ES-derived cells after hepatic 
      differentiation, ES-HPC). Peak levels for HNF-1alpha, -3alpha, -4alpha and -6 
      were detected in early liver development at d9.5 and d11.5. C/EBPalpha and beta 
      were most abundantly expressed in adult liver. ALB mRNA increased steadily from 
      d10.5 on and was maximally present in adult liver. AFP was present at d9.5, 
      peaked at d15.5 and dramatically declined in mature liver tissue. Based on 
      immunofluorescence, ALB and AFP were expressed in approximately 20% of ES-HPC. 
      While expression of HNF-3, 4 and 6 reached levels similar to adult hepatocytes, 
      ALB and AFP expression was several orders of magnitude lowerthan in adult tissue 
      or cells. Stages of liver organogenesis are characterized by specific expression 
      patterns of developmentally regulated genes. With sophisticated differentiation 
      protocols, hepatic gene expression can be induced in a proportion of ES cells 
      with gene expression patterns similar to early fetal liver.
FAU - Jochheim, Andrea
AU  - Jochheim A
AD  - Hannover Medical School, Center of Internal Medicine, Department of 
      Gastroenterology, Hepatology and Endocrinology, Hannover, Germany.
FAU - Hillemann, Tina
AU  - Hillemann T
FAU - Kania, Gabriela
AU  - Kania G
FAU - Scharf, Jennifer
AU  - Scharf J
FAU - Attaran, Masoumeh
AU  - Attaran M
FAU - Manns, Michael P
AU  - Manns MP
FAU - Wobus, Anna M
AU  - Wobus AM
FAU - Ott, Michael
AU  - Ott M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Spain
TA  - Int J Dev Biol
JT  - The International journal of developmental biology
JID - 8917470
RN  - 0 (Albumins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - 0 (alpha-Fetoproteins)
SB  - IM
MH  - Albumins/genetics
MH  - Animals
MH  - Animals, Newborn
MH  - Cell Differentiation
MH  - Fetus/cytology/*metabolism
MH  - *Gene Expression Profiling
MH  - Hepatocytes/*cytology/*metabolism
MH  - Liver/*cytology/*embryology/metabolism
MH  - Mice
MH  - Microscopy, Fluorescence
MH  - Phenotype
MH  - RNA, Messenger/genetics/metabolism
MH  - Stem Cells/*cytology/metabolism
MH  - Transcription Factors/genetics
MH  - alpha-Fetoproteins/genetics
EDAT- 2004/03/10 05:00
MHDA- 2004/09/25 05:00
CRDT- 2004/03/10 05:00
PHST- 2004/03/10 05:00 [pubmed]
PHST- 2004/09/25 05:00 [medline]
PHST- 2004/03/10 05:00 [entrez]
AID - 10.1387/ijdb.15005571 [doi]
PST - ppublish
SO  - Int J Dev Biol. 2004 Feb;48(1):23-9. doi: 10.1387/ijdb.15005571.