Clonal Identification and Characterization of Self-renewing Pluripotent Stem Cells in the Developing Liver

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2002 Jan 10

PMID 11781341

Citations 87

Authors

Atsushi Suzuki

Y W Zheng

Shin Kaneko

Masafumi Onodera

Katashi Fukao

Hiromitsu Nakauchi

Hideki Taniguchi

Affiliations

Soon will be listed here.

Abstract

Using flow cytometry and single cell-based assays, we prospectively identified hepatic stem cells with multilineage differentiation potential and self-renewing capability. These cells could be clonally propagated in culture where they continuously produced hepatocytes and cholangiocytes as descendants while maintaining primitive stem cells. When cells that expanded in vitro were transplanted into recipient animals, they morphologically and functionally differentiated into hepatocytes and cholangiocytes with reconstitution of hepatocyte and bile duct structures. Furthermore, these cells differentiated into pancreatic ductal and acinar cells or intestinal epithelial cells when transplanted into pancreas or duodenal wall. These data indicate that self-renewing pluripotent stem cells persist in the developing mouse liver and that such cells can be induced to become cells of other organs of endodermal origin under appropriate microenvironment. Manipulation of hepatic stem cells may provide new insight into therapies for diseases of the digestive system.

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References

Sasaki K, Adachi S, Yamamoto T, Murakami T, Tanaka K, Takahashi M . Effects of denaturation with HCl on the immunological staining of bromodeoxyuridine incorporated into DNA. Cytometry. 1988; 9(1):93-6. DOI: 10.1002/cyto.990090115. View

Deutsch G, Jung J, Zheng M, Lora J, Zaret K . A bipotential precursor population for pancreas and liver within the embryonic endoderm. Development. 2001; 128(6):871-81. DOI: 10.1242/dev.128.6.871. View

Sell S, Dunsford H . Evidence for the stem cell origin of hepatocellular carcinoma and cholangiocarcinoma. Am J Pathol. 1989; 134(6):1347-63. PMC: 1879951. View

Paulus U, Loeffler M, Zeidler J, Owen G, Potten C . The differentiation and lineage development of goblet cells in the murine small intestinal crypt: experimental and modelling studies. J Cell Sci. 1993; 106 ( Pt 2):473-83. DOI: 10.1242/jcs.106.2.473. View

Uehara Y, Minowa O, Mori C, Shiota K, KUNO J, Noda T . Placental defect and embryonic lethality in mice lacking hepatocyte growth factor/scatter factor. Nature. 1995; 373(6516):702-5. DOI: 10.1038/373702a0. View

Crosby H, Kelly D, Strain A . Human hepatic stem-like cells isolated using c-kit or CD34 can differentiate into biliary epithelium. Gastroenterology. 2001; 120(2):534-44. DOI: 10.1053/gast.2001.21175. View

Rao M, Dwivedi R, Yeldandi A, Subbarao V, Tan X, Usman M . Role of periductal and ductular epithelial cells of the adult rat pancreas in pancreatic hepatocyte lineage. A change in the differentiation commitment. Am J Pathol. 1989; 134(5):1069-86. PMC: 1879886. View

Hu Z, Evarts R, Fujio K, Marsden E, Thorgeirsson S . Expression of hepatocyte growth factor and c-met genes during hepatic differentiation and liver development in the rat. Am J Pathol. 1993; 142(6):1823-30. PMC: 1886980. View

Matsusaka S, Tsujimura T, Toyosaka A, Nakasho K, Sugihara A, Okamoto E . Role of c-kit receptor tyrosine kinase in development of oval cells in the rat 2-acetylaminofluorene/partial hepatectomy model. Hepatology. 1999; 29(3):670-6. DOI: 10.1002/hep.510290304. View

10.

Shiojiri N . The origin of intrahepatic bile duct cells in the mouse. J Embryol Exp Morphol. 1984; 79:25-39. View

11.

Till J, McCulloch E . A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res. 1961; 14:213-22. View

12.

Schmidt C, Bladt F, Goedecke S, Brinkmann V, Zschiesche W, Sharpe M . Scatter factor/hepatocyte growth factor is essential for liver development. Nature. 1995; 373(6516):699-702. DOI: 10.1038/373699a0. View

13.

Overturf K, Finegold M, Grompe M . The repopulation potential of hepatocyte populations differing in size and prior mitotic expansion. Am J Pathol. 1999; 155(6):2135-43. PMC: 1866923. DOI: 10.1016/S0002-9440(10)65531-9. View

14.

Fujio K, Evarts R, Hu Z, Marsden E, Thorgeirsson S . Expression of stem cell factor and its receptor, c-kit, during liver regeneration from putative stem cells in adult rat. Lab Invest. 1994; 70(4):511-6. View

15.

Petersen B, Goff J, Greenberger J, Michalopoulos G . Hepatic oval cells express the hematopoietic stem cell marker Thy-1 in the rat. Hepatology. 1998; 27(2):433-45. DOI: 10.1002/hep.510270218. View

16.

Grisham J, Coleman W, Smith G . Isolation, culture, and transplantation of rat hepatocytic precursor (stem-like) cells. Proc Soc Exp Biol Med. 1993; 204(3):270-9. DOI: 10.3181/00379727-204-43663. View

17.

Suzuki A, Zheng Y, Kondo R, Kusakabe M, Takada Y, Fukao K . Flow-cytometric separation and enrichment of hepatic progenitor cells in the developing mouse liver. Hepatology. 2000; 32(6):1230-9. DOI: 10.1053/jhep.2000.20349. View

18.

Michalopoulos G, Defrances M . Liver regeneration. Science. 1997; 276(5309):60-6. DOI: 10.1126/science.276.5309.60. View

19.

Pack R, Heck R, Dienes H, Oesch F, Steinberg P . Isolation, biochemical characterization, long-term culture, and phenotype modulation of oval cells from carcinogen-fed rats. Exp Cell Res. 1993; 204(2):198-209. DOI: 10.1006/excr.1993.1025. View

20.

Raff M, Lillien L, Richardson W, Burne J, Noble M . Platelet-derived growth factor from astrocytes drives the clock that times oligodendrocyte development in culture. Nature. 1988; 333(6173):562-5. DOI: 10.1038/333562a0. View