On the origin of stellate cells: mesodermal, endodermal or neuro-ectodermal?

Geerts, Albert

doi:10.1016/j.jhep.2003.12.006

Cited by 78 publications

(61 citation statements)

References 31 publications

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“…Stellate cells appear in the second half of the third month of gestation in human development (193). At birth in rats, stellate cells have still not reached their final size, which requires an additional 5 weeks (680).…”

Section: A Embryologic Origin(s)mentioning

confidence: 99%

“…In humans, a population of cells has been characterized in midgestation of embryonic liver development using specific antibodies that are CD34 ϩ cytokeratin (CK)7/8 ϩ and also express CD13, CD59, nerve growth factor receptor (NGFR), desmin, and ␣-smooth muscle actin (␣-SMA), leading the authors to conclude that they represent embryonic precursors of adult stellate cells derived from endoderm (193,624). These cells were larger with more cytoplasm than CD34 ϩ CK7/8 Ϫ cells and had cytoplasmic projections, also characteristic of stellate cells.…”

Section: A Embryologic Origin(s)mentioning

confidence: 99%

“…However, fate mapping studies of neural crest-derived cells in developing mouse liver have recently failed to localize to hepatic stellate cells during late gestation (94,193), undermining the possibility of a neural origin.…”

Section: A Embryologic Origin(s)mentioning

confidence: 99%

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Hepatic Stellate Cells: Protean, Multifunctional, and Enigmatic Cells of the Liver

Friedman

2008

Physiological Reviews

2,419

2,549

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The hepatic stellate cell has surprised and engaged physiologists, pathologists, and hepatologists for over 130 years, yet clear evidence of its role in hepatic injury and fibrosis only emerged following the refinement of methods for its isolation and characterization. The paradigm in liver injury of activation of quiescent vitamin A-rich stellate cells into proliferative, contractile, and fibrogenic myofibroblasts has launched an era of astonishing progress in understanding the mechanistic basis of hepatic fibrosis progression and regression. But this simple paradigm has now yielded to a remarkably broad appreciation of the cell's functions not only in liver injury, but also in hepatic development, regeneration, xenobiotic responses, intermediary metabolism, and immunoregulation. Among the most exciting prospects is that stellate cells are essential for hepatic progenitor cell amplification and differentiation. Equally intriguing is the remarkable plasticity of stellate cells, not only in their variable intermediate filament phenotype, but also in their functions. Stellate cells can be viewed as the nexus in a complex sinusoidal milieu that requires tightly regulated autocrine and paracrine cross-talk, rapid responses to evolving extracellular matrix content, and exquisite responsiveness to the metabolic needs imposed by liver growth and repair. Moreover, roles vital to systemic homeostasis include their storage and mobilization of retinoids, their emerging capacity for antigen presentation and induction of tolerance, as well as their emerging relationship to bone marrow-derived cells. As interest in this cell type intensifies, more surprises and mysteries are sure to unfold that will ultimately benefit our understanding of liver physiology and the diagnosis and treatment of liver disease.

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Section: A Embryologic Origin(s)mentioning

confidence: 99%

Section: A Embryologic Origin(s)mentioning

confidence: 99%

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Hepatic Stellate Cells: Protean, Multifunctional, and Enigmatic Cells of the Liver

Friedman

2008

Physiological Reviews

2,419

2,549

View full text Add to dashboard Cite

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“…Lineage tracing of the Wilms tumor suppressor gene-expressing (Wt1-expressing) cells and mesoderm posterior 1-expressing cells in mice showed that hepatic stellate cells develop from the septum transversum-derived mesothelium lining the liver (25,26), suggestive of a mesodermal origin. On the other hand, stellate cells in the human fetal liver express CD34 and cytokeratin-7/8, connecting them to an endodermal origin (27,28). Along this theme, hepatic epithelial cells are thought to transdifferentiate into hepatic stellate cells in the injured liver through epithelial-mesenchymal transition (EMT) (29).…”

Section: Hepatic Stellate Cells In Liver Developmentmentioning

confidence: 99%

Hepatic stellate cells in liver development, regeneration, and cancer

Yin¹,

Evason²,

Asahina³

et al. 2013

J. Clin. Invest.

602

567

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Hepatic stellate cells are liver-specific mesenchymal cells that play vital roles in liver physiology and fibrogenesis. They are located in the space of Disse and maintain close interactions with sinusoidal endothelial cells and hepatic epithelial cells. It is becoming increasingly clear that hepatic stellate cells have a profound impact on the differentiation, proliferation, and morphogenesis of other hepatic cell types during liver development and regeneration. In this Review, we summarize and evaluate the recent advances in our understanding of the formation and characteristics of hepatic stellate cells, as well as their function in liver development, regeneration, and cancer. We also discuss how improved knowledge of these processes offers new perspectives for the treatment of patients with liver diseases.

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“…Despite intensive research for decades, HSCs have remained enigmatic (2). For instance, stellate cells express molecular markers of different germ layers, which impede a clear statement about their origin (3). The presence of glial fibrillary acidic protein (GFAP) and many other neuroectodermal proteins in stellate cells (4) led to the view that they may derive from the neural crest.…”

Section: Introductionmentioning

confidence: 99%