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N Shiojiri

Publications and source records attributed to N Shiojiri.

26 records · Page 2Linked to original sources

Preferential differentiation of the bile ducts along the portal vein in the development of mouse liver.

The development of bile ducts in the mouse liver was studied histochemically, with special reference to their preferential differentiation around the portal vein. Both portal vein and hepatic vein shared a common origin, the omphalomesenteric vein. In the early development of the liver, haematopoietic cells were predominant around both veins. With the progressive development of intrahepatic bile ducts, the following three steps were observed: cluster formation of type I hepatocytes around the portal vein, formation of primitive bile duct structures and basal lamina, then formation of ducts surrounded by connective tissue structures composed of type I and type III collagens and lectin-binding sites, which were predominant around the portal vein compared to the hepatic vein. These results suggest that the deposition of abundant connective tissue structures around the portal vein is a prerequisite for the cell differentiation and basal lamina formation in the bile duct precursors. A possible mechanism of the aggregation of type I hepatocytes around the portein vein is also discussed.

Animals↗

Cell lineages and oval cell progenitors in rat liver development.

We determined whether the formation of the hepatic primordium in the rat is associated with the expression of liver-specific markers. Further, we examined the origin of intra- and extrahepatic bile ducts and tried to establish whether there are cell types in the developing liver that might correspond to "stem-like" cells ("oval cells") that proliferate during carcinogenesis and toxic injury in adult livers. Using in situ hybridization and immunohistochemical methods, we show that alpha-fetoprotein (AFP) mRNA is detected in cells of the ventral foregut at 10.5 days of development and that the protein is first detected 1 day later. Thus, AFP transcription occurs before liver morphogenesis, and translation of the protein is first detected when liver cords are being formed, indicating that AFP expression in endodermal cells signals their commitment toward the liver lineage. Although albumin is considered a trait of differentiated hepatocytes, its mRNA was first detected just 1 day later than the AFP message. An analysis of the expression of lineage-specific cytokeratins (cytokeratins 7, 9, 18, and 19), surface markers, and histochemical determination of gamma-glutamyl transferase activity and glycogen revealed that (a) hepatoblasts undergo gradual maturation throughout liver development, (b) AFP- and albumin-containing hepatoblasts gave rise to intra- and extrahepatic bile ducts, and (c) hepatoblasts forming primitive intrahepatic bile ducts during liver development have markers similar to those expressed by stem-like cells that proliferate during liver carcinogenesis.

Animals↗

Oval cell proliferation and the origin of small hepatocytes in liver injury induced by D-galactosamine.

Oval cells may function as facultative liver stem cells and tumor progenitors in liver carcinogenesis. The authors determined whether oval cells proliferate and if small hepatocytes might be generated from epithelial cell progenitors in noncarcinogenic liver injury. The authors found that oval cells similar to those detected in early carcinogenesis proliferate in response to D-galactosamine (GaIN). Oval cells expressed gamma-glutamyl transpeptidase activity, bile duct-type cytokeratins and peanut agglutinin binding. Two unusual types of hepatocytes also appeared after injury: small hepatocytes (less than or equal to 16 microns in diameter) and hepatocytes lining atypical ductlike structures. In situ hybridization studies showed that the fetal form of alphafetoprotein mRNA was expressed by many oval cells, some bile duct cells, and occasional hepatocytes. By following the fate of epithelial cells labeled early after GaIN administration, the authors conclude that duct cells can generate both oval cells and small hepatocytes in response to GaIN.

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Lymphoid follicle formation in the bursa of Fabricius of the chick embryo.

The colonisation of lymphoid stem cells and the following lymphoid follicle formation in the bursa of Fabricius of the chick embryo was studied histochemically and morphologically. Most basophilic haematopoietic stem cells first appeared in the mesenchyme of the distal bursa at 7 and 8 days. Basophilic cells were also seen in the loose connective tissue near the distal bursa, and in the vessels which were located dorsal to the distal bursa. They began to invade the epithelium at 10 and 11 days of incubation by digesting the basal laminar components which the fluorescent lectin probes stained. Haematopoietic stem cells were in close association with the extracellular matrix in the mesenchyme and contained abundant F-actin. F-actin also increased in the epithelial cells surrounding basophilic haematopoietic stem cells during lymphoid follicle formation. F-actin in migrating haematopoietic stem cells and epithelial cells might be involved in the migration of haematopoietic cells and the histogenesis of the lymphoid follicles. Granulopoiesis occurred mainly in the bursal mesenchyme, but some granulocytes were seen in the epithelium. The results support the extrinsic origin of the bursal lymphoid stem cells and their active migration towards the epithelium in the chick embryo. Cell-cell interactions and tissue interactions in the lymphoid follicle formation are also discussed.

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Development of Dolichos biflorus agglutinin (DBA) binding sites in the bile duct of the embryonic mouse liver.

The distribution of binding sites for Dolichos biflorus agglutinin (DBA) was studied by histochemical staining in the embryonic mouse liver. The liver primordium consists of cranial and caudal diverticula. DBA bound to the pseudostratified endodermal cells of the caudal hepatic diverticulum, and also to some endodermal cells of the cranial one. Most extrahepatic bile duct cells and all epithelial cells of the gall bladder were consistently DBA-positive. In intrahepatic bile ducts and their precursors, the DBA binding sites showed a patchy distribution. Most hepatocytes were DBA-negative, though some young hepatocytes were DBA-positive. The results suggest that DBA binding sites are useful markers of epithelial cells of the gall bladder and the bile ducts, especially the extrahepatic bile duct. Differentiation of bile duct cells was also discussed with special reference to the developmental change of the distribution of the DBA binding sites.

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Secondary joining of the bile ducts during the hepatogenesis of the mouse embryo.

Development of the bile duct system of the mouse embryo was studied histologically and by an immunofluorescent technique. The hepatic primordium consisted of cranial and caudal portions. In the liver of young embryos, the hepatic cords were present in the presumptive cystic duct epithelium, and the histology of the presumptive cystic duct epithelium near the hilus was similar to that of the hilus epithelium. The results suggest that at least a part of the cystic duct epithelium develops from the cranial diverticulum of the hepatic primordium. Lumen structures were precursors of intrahepatic bile ducts and originated from type I (immature) hepatocytes. The lumina of the lumen structures appeared near the hilus area first, but most were discontinuous with those of the hepatic ducts. With the progress of development, the discontinuous lumen structures became distributed around the portal vein branches in the central part of the liver parenchyma, and gradually connected with each other and also with hepatic ducts. The discontinuous laminin immunofluorescence also appeared in the endodermal cells around the portal vein branches at the younger stages. Therefore, it is conceivable that the intrahepatic bile ducts originate from discrete cell populations of type I hepatocytes around the portal vein branches and subsequently become confluent, but not from the cells of hepatic ducts.

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The origin of intrahepatic bile duct cells in the mouse.

The origin of the intrahepatic bile ducts in the embryonic mouse liver was investigated. At 12.5 and 13.5 gestation days in the C3H/Tw strain mouse, the liver parenchyma contains morphologically and histochemically homogeneous immature hepatocytes but not bile duct cells. When the liver fragments were cultured in the testis, immature hepatocytes differentiated into large hepatocytes for the most part and also into bile duct cells. In contrast, when the similar liver fragments were cultured under the skin of newborn mice, bile duct cells differentiated much earlier in all transplants than those cultured in the testis. These bile duct cells were considered to be the intrahepatic bile duct cells, since they did not form biliary glands but possessed a basal lamina and histochemical characteristics of intrahepatic bile duct cells of the normal liver. The origin of the endodermal epithelial cells in the mouse liver is discussed with special attention to the differentiation of the intrahepatic bile duct cells from the immature hepatocytes.

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Enzymo- and immunocytochemical analyses of the differentiation of liver cells in the prenatal mouse.

Differentiation of the endodermal cells of the mouse liver was studied enzymo- and immunocytochemically by analyzing the cellular localization of alphafoetoprotein (AFP), glycogen, and alkaline phosphatase (ALP) and 5'-nucleotidase (5'-Nase) activities. 1. In 8.5-day foetuses, AFP appears in some endodermal cells of the anterior intestinal portal region. The cells of the cranial diverticulum contain much AFP at 9.5 days, while those of the caudal diverticulum contain less AFP. 2. In 9.5- to 15.5-day foetuses, hepatocytes are intensely fluorescent for AFP. After 16.5 days less-positive hepatocytes increase in number. AFP is still present in a few hepatocytes of 14-day-old postnatal mice. ALP and 5'-Nase activities appear in a small proportion of hepatocytes at 13.5 and 14.5 days of embryonal life, respectively. At 15.5 days, many hepatocytes possess these enzyme activities, and initiate accumulation of glycogen. AFP-containing hepatocytes type I (gestation day 9.5-16.5) successively acquire ALP and 5'-Nase activities and accumulate glycogen, and then differentiate into hepatocytes type II after gestation day 17.5. 3. Endodermal cells constituting lumen structures in the liver trabeculae are the precursor of the intrahepatic bile duct cells. They possess much AFP, but no glycogen and no ALP activity, and are similar to hepatocytes type I. Since immature hepatic duct cells also possess much AFP, but no glycogen, and no ALP and 5'-Nase activities, they are similar to endodermal cells of the lumen structures. Therefore, that the endodermal cells of the lumen structures are the intermediate cells between hepatocytes type I and hepatic duct cells may be conceivable.

5'-Nucleotidase↗