Endoderm-Specific Gene Expression in Embryonic Stem Cells Differentiated to Embryoid Bodies

Abe, Koichiro; Niwa, Hitoshi; Iwase, Katsuro; Takao, Masaki; Mori, Masataka; Abe, Shinichi; Abe, Kuniya; Yamamura, Ken Ichi

doi:10.1006/excr.1996.0340

Cited by 192 publications

(140 citation statements)

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“…This is somehow in contrast with the fact that in developing embryos, HNF-6 is expressed in a lineage-restricted manner [17]. However, several lineage-restricted factors, which include HNF-1α, HNF-1β and PDX-1 [29,34,35], are known to be expressed in undifferentiated ES cells and we show here that this is also the case for NGN-3. More importantly, we found that HNF-6 is also expressed in the outer layer of the EBs, which is consistent with the known expression of HNF-6 in the yolk sac [36].…”

Section: Discussioncontrasting

confidence: 59%

“…Indeed, in animals, the visceral endoderm produces a number of proteins such as, for instance, alpha foetoprotein, transthyretin, apolipoproteins and glucose transporters which are also found in the outer cell layer of the EBs [27]. In addition, tissuespecific transcriptional regulators of these genes in the visceral endoderm are functional in the outer layer of EBs [28,29]. Insulin is also expressed in the yolk sac visceral endoderm [30], which is consistent with our present observation that insulin is produced by the outer cell layer of EBs.…”

Section: Discussionmentioning

confidence: 99%

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HNF-6-independent differentiation of mouse embryonic stem cells into insulin-producing cells

Houard¹,

Rousseau²,

Lemaigre³

2003

Diabetologia

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Aims/hypothesis. Embryonic stem cells, when grown as embryoid bodies, spontaneously generate insulinproducing cells which could be used in therapy of diabetes mellitus, provided that their selection and differentiation are optimized. To achieve such optimization, one needs to know whether the differentiation of cells in embryoid bodies mimicks that of pancreatic beta cells in embryos. To address this question we verified if the differentiation of the insulin-producing cells in embryoid bodies requires Hepatocyte Nuclear Factor-6 (HNF-6), a transcription factor known to control pancreatic endocrine differentiation in embryos. Methods. We generated mouse Hnf6−/− embryonic stem cells and grew them as embryoid bodies. The expression of HNF-6, insulin, and transcription factors that are regulated by HNF-6 in developing pancreas was compared in wild-type and Hnf6−/− embryoid bodies. Results.No difference was observed in the expression of insulin between wild-type and Hnf6−/− embryoid bodies. In both cases insulin was expressed in the outer layer of cells, which is similar to the visceral endoderm. In wild-type embryoid bodies HNF-6 was transiently expressed in the outer layer of cells, but was not co-expressed with insulin. The expression of genes that are targets of HNF-6 in developing pancreas was unaffected in Hnf6−/− embryoid bodies. Conclusion/interpretation. In contrast to the development of pancreatic beta cells, the differentiation of insulin-producing cells in embryoid bodies did not require HNF-6. Thus, the differentiation mechanism of insulin-producing cells in embryoid bodies differs from that of the beta cells and it is likely to resemble that of insulin-producing cells in the visceral endoderm. [Diabetologia (2003) 46:378-385]

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Section: Discussioncontrasting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

HNF-6-independent differentiation of mouse embryonic stem cells into insulin-producing cells

Houard¹,

Rousseau²,

Lemaigre³

2003

Diabetologia

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“…During differentiation of ES cells to EBs, AFP is first expressed in the EB outer layer, which is the equivalent of embryonic primitive endoderm that develops into the visceral endoderm [8][9][10]. The early embryonic expression pattern of AFP, other mesodermal proteins, and some hepatic-specific genes is essentially recapitulated during the development of ES cells into EBs [8][9][10][11][12]. Based on this background information, we rationalized that AFP may be a good marker for identifying endodermal progenitor cells that constitute a committed hepatic lineage from differentiated ES cells.…”

Section: ® Original Articlementioning

confidence: 99%

AFP ⁺ , ESC‐Derived Cells Engraft and Differentiate into Hepatocytes in Vivo

et al. 2002

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“…Since the first reports on differentiation of mouse ES cells into endodermal cells [Abe et al, 1996;Levinson-Dushnik and Benvenisty, 1997], many studies demonstrated differentiation of ES cells into hepatic-like cells. In Table I, we summarize the studies on differentiation of mouse and human ES cells into hepatic-like cells.…”

Section: Embryonic Stem Cells and Hepatocytesmentioning

confidence: 99%

“…Spontaneous differentiation of mouse ES cells occurs when the cells are grown in suspension and form EBs [Abe et al, 1996;Chinzei et al, 2002;Jones et al, 2002;Miyashita et al, 2002;Yamada et al, 2002;Asahina et al, 2004;Kumashiro et al, 2005]. In order to direct the differentiation towards the endoderm lineage, various growth factors were used.…”

Section: Embryonic Stem Cells and Hepatocytesmentioning

confidence: 99%

Study of hepatocyte differentiation using embryonic stem cells

Lavon

Benvenisty

2005

J of Cellular Biochemistry

114

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The liver has many crucial functions including metabolizing dietary molecules, detoxifying compounds, and storing glycogen. The hepatocytes, comprising most of the liver organ, progressively modify their gene expression profile during the fetal development according to their roles in the different phases of development. Embryonic stem (ES) cells serve as a major tool in understanding liver development. These cells may also serve as a source of hepatic cells for cellular therapy. In this review, we aim to summarize the research that has been performed in the field of hepatocyte differentiation from mouse and human ES cells. We discuss the various methodologies for the differentiation of ES cells towards hepatic cells using either spontaneous or directed differentiation protocols. Although many protocols for differentiating ES cells to hepatic cells have been developed, the analysis of their status is not trivial and can lead to various conclusions. Hence, we discuss the issues of analyzing hepatocytes by means of the specificity of the markers for hepatocytes and the status of the cells as fetal or adult hepatocytes.

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Endoderm-Specific Gene Expression in Embryonic Stem Cells Differentiated to Embryoid Bodies

Cited by 192 publications

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HNF-6-independent differentiation of mouse embryonic stem cells into insulin-producing cells

HNF-6-independent differentiation of mouse embryonic stem cells into insulin-producing cells

AFP ⁺ , ESC‐Derived Cells Engraft and Differentiate into Hepatocytes in Vivo

Study of hepatocyte differentiation using embryonic stem cells

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Endoderm-Specific Gene Expression in Embryonic Stem Cells Differentiated to Embryoid Bodies

Cited by 192 publications

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HNF-6-independent differentiation of mouse embryonic stem cells into insulin-producing cells

HNF-6-independent differentiation of mouse embryonic stem cells into insulin-producing cells

AFP + , ESC‐Derived Cells Engraft and Differentiate into Hepatocytes in Vivo

Study of hepatocyte differentiation using embryonic stem cells

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AFP ⁺ , ESC‐Derived Cells Engraft and Differentiate into Hepatocytes in Vivo