Link found between pancreas, liver cells

Philadelphia research expected to give insight into growth of cancer


PHILADELPHIA - Cells that develop into the liver can also give rise to part of the pancreas, according to researchers at the Fox Chase Cancer Center here.

The finding counters the assumption that during the early stages of mammalian development, the liver and pancreas cells develop from separate lineages.

Kenneth S. Zaret and his research team had originally been studying the development of the liver in mouse embryos and then discovered that the ventral part of the pancreas develops at the same time as the liver and from the same type of endoderm cells.

Significance of findings

In discussing the significance of the findings, Zaret said: "It offers an explanation for the puzzling emergence of liver cells in the pancreas during certain pathological states. The work provides a new direction for the pancreatic development field, since it reveals a common relation between the pancreas and liver, overturning the previously held notion that there was no developmental link between the two.

"Understanding how signaling and gene regulatory factors control the development of the liver and ventral pancreas should provide important insights on how to control the differentiation state of life-threatening cells which surface during carcinogenesis or chronic tissue damage, as well as during metabolic diseases."

Different domains of the endoderm, an early embryonic tissue, normally differentiate into liver, lung, pancreas, thyroid, and intestine; yet how these diverse tissue domains are specified, and whether each tissue domain can give rise to other tissue derivatives, has been unclear.

Differentiation is the process whereby embryonic cells become specialized in structure and function, and organize into the tissues and organs that make up the adult organism. The goal of Zaret's research was to understand principles by which different cell types arise from a common starting point.

Research hypothesis

Zaret's group hypothesized that early embryonic cells that normally become the liver may also have the capacity to become the ventral part of the pancreas. They previously developed techniques for isolating cells from the ventral endoderm of a mouse embryo and for culturing the cells in the laboratory, allowing the researchers to follow the generation of the liver or pancreatic cell lineages.

Earlier, they used this culture method to show that fibroblast growth factor (FGF), a signal secreted from embryonic heart tissue, would cause nearby ventral endoderm cells to initiate liver development. The embryonic liver normally originates next to the cardiac domain.

In the present study, Zaret's group showed that in the absence of cardiac FGF signaling, the ventral endoderm cells would initiate pancreas development instead of that for liver. They concluded that by default, the cells in this domain of the endoderm will differentiate into pancreas cells, and the role of FGF signaling from the heart is to divert some of the endoderm cells from a pancreatic fate to a liver fate.

The embryonic precursor cells that Zaret's laboratory studied therefore undergo a choice whereby they can become either the liver or the ventral pancreas, depending on the presence of a signaling factor. The researchers could control endoderm differentiation into either early liver cells or early pancreas cells by manipulating the cell culture conditions.

Zaret's research is supported by a grant from the Institute of General Medical Sciences at the National Institutes of Health. His studies on cell signaling and genetic control are an example of the importance of basic research to the control of health and disease.

He conducted this research in collaboration with Joonil Jung at Fox Chase and Gail Deutsch, Minghua Zheng, and Jose Lora of Brown University. The study was published in a recent issue of Development .

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