Hematopoietic progenitors from early murine fetal liver possess hepatic differentiation potential. 2008

Satish Khurana, and Asok Mukhopadhyay
Stem Cell Biology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.

Bipotential hepatoblasts differentiate into hepatocytes and cholangiocytes during liver development. It is believed that hepatoblasts originate from endodermal tissue. Here, we provide evidence for the presence of hepatic progenitor cells in the hematopoietic compartment at an early stage of liver development. Flow cytometric analysis showed that at early stages of liver development, approximately 13% of CD45(+) cells express Delta-like protein-1, a marker of hepatoblasts. Furthermore, reverse transcriptase-PCR data suggest that many hepatic genes are expressed in these cells. Cell culture experiments confirmed the hepatic differentiation potential of these cells with the loss of the CD45 marker. We observed that both hematopoietic activity in Delta-like protein-1(+) cells and hepatic activity in CD45(+) cells were high at embryonic day 10.5 and declined thereafter. Clonal analysis revealed that the hematopoietic fraction of fetal liver cells at embryonic day 10.5 gave rise to both hepatic and hematopoietic colonies. The above results suggest a common source of these two functionally distinct cell lineages. In utero transplantation experiments confirmed these results, as green fluorescent protein-expressing CD45(+) cells at the same stage of development yielded functional hepatocytes and hematopoietic reconstitution. Since these cells were unable to differentiate into cytokeratin-19-expressing cholangiocytes, we distinguished them from hepatoblasts. This preliminary study provides hope to correct many liver diseases during prenatal development via transplantation of fetal liver hematopoietic cells.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D008822 Mice, Transgenic Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN. Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D002135 Calcium-Binding Proteins Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS. Calcium Binding Protein,Calcium-Binding Protein,Calcium Binding Proteins,Binding Protein, Calcium,Binding Proteins, Calcium,Protein, Calcium Binding,Protein, Calcium-Binding
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D005260 Female Females
D006412 Hematopoietic Stem Cells Progenitor cells from which all blood cells derived. They are found primarily in the bone marrow and also in small numbers in the peripheral blood. Colony-Forming Units, Hematopoietic,Progenitor Cells, Hematopoietic,Stem Cells, Hematopoietic,Hematopoietic Progenitor Cells,Cell, Hematopoietic Progenitor,Cell, Hematopoietic Stem,Cells, Hematopoietic Progenitor,Cells, Hematopoietic Stem,Colony Forming Units, Hematopoietic,Colony-Forming Unit, Hematopoietic,Hematopoietic Colony-Forming Unit,Hematopoietic Colony-Forming Units,Hematopoietic Progenitor Cell,Hematopoietic Stem Cell,Progenitor Cell, Hematopoietic,Stem Cell, Hematopoietic,Unit, Hematopoietic Colony-Forming,Units, Hematopoietic Colony-Forming
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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