Hepatic stellate cells do not derive from the neural crest.
OBJECTIVE
Hepatic stellate cells (HSC) have been hypothesised to derive from the neural crest, based on their expression of multiple neural/neuroendocrine features and their contacts with autonomic nerve endings.


METHODS
We studied the emergence of HSC in the liver during embryonic development in a transgenic mouse line expressing yellow fluorescent protein (YFP) in all neural crest cells and their derivatives. Cellular YFP expression in these mice was compared with desmin expression between embryonic day (E) 11.5 and adulthood.


RESULTS
YFP was abundantly expressed in neural crest cells delaminating from the neural tube and in all known neural crest-derived structures and cell populations. In particular, YFP expressing cells perfectly mimicked the spatial and temporal pattern of enteric nervous system development from neural crest cells migrating from the postotic region. Cells within the adrenal medulla were also YFP positive. Analysis of the liver showed that desmin-expressing, stellate-shaped, perisinusoidally located HSC were evident from E11.5 onwards. However, no detectable YFP expression was seen in the developing liver or in HSC, from E11.5 until adulthood.


CONCLUSIONS
These findings suggest HSC do not descend from the neural crest, and therefore may derive from the septum transversum mesenchyme, from endoderm or from the mesothelial liver capsule.
Cassiman
David
D
Department of Hepatology, University Hospital Gasthuisberg, University of Leuven, Herestraat 49, B-3000 Leuven, Belgium. david.cassiman@med.kuleuven.ac.be
Barlow
Amanda
A
Vander Borght
Sara
S
Libbrecht
Louis
L
Pachnis
Vassilis
V
D000818:Animals; D001426:Bacterial Proteins / Q000032:analysis / Q000235:genetics; D005260:Female; D022781:Hepatocytes / Q000166:cytology*; D019426:Integrases / Q000235:genetics; D008099:Liver / Q000737:chemistry / Q000166:cytology / Q000196:embryology*; D008164:Luminescent Proteins / Q000032:analysis / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009432:Neural Crest / Q000737:chemistry / Q000166:cytology / Q000196:embryology*; D011401:Promoter Regions, Genetic; D014764:Viral Proteins / Q000235:genetics; D051155:Wnt1 Protein / Q000235:genetics
D001426:Bacterial Proteins; D008164:Luminescent Proteins; D014764:Viral Proteins; D051155:Wnt1 Protein; C054562:yellow fluorescent protein, Bacteria; C045073:Cre recombinase; D019426:Integrases