Induction of hepatic differentiation in embryonic stem cells by co-culture with embryonic cardiac mesoderm

Jeffrey Fair, Bruce A. Cairns, Michael LaPaglia, Jian Wang, Anthony A. Meyer, Hyung Kim, Seigo Hatada, Oliver Smithies, Larysa Pevny

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Background. Modifications in vitro have been used to direct embryonic stem (ES) cells toward endodermal phenotypes including hepatocytes; however, developmental correlates and evidence of biologic activity is lacking, and critical cell-cell interactions have not been investigated. In this study, we hypothesized that cardiac raesoderra (CM) signals ES cells in co-culture to undergo differentiation toward early hepatocyte lineage as determined by morphology and induction of genes essential for endodermal competence and hepatocyte development. Methods. Green fluorescent protein ES derived from A129 mice were cultured with or without embryonic chick cardiac mesoderm. Cultures from day 1, 2, and 4 were analyzed for colony formation and ES morphology and 106 ES-derived cells were isolated for mRNA analysis. Results. ES in co-culture with CM displayed colony formation, polymorphic appearance, and definitive interface with CM. In addition, ES + CM co-culture activated crucial transcription factors (sox 17α, HNF3β, and GATA 4) required for hepatocyte development by day 1. mRNA for albumin and especially α-fetoprotein were also increased by culture days 2 and 4. Conclusions. ES cells co-cultured with CM display morphology and gene expression pattern required for hepatocyte differentiation and appear to recapitulate the molecular events of hepatogenesis.

Original languageEnglish (US)
Pages (from-to)189-196
Number of pages8
JournalSurgery
Volume134
Issue number2
DOIs
StatePublished - Aug 1 2003
Externally publishedYes

Fingerprint

Mesoderm
Embryonic Stem Cells
Coculture Techniques
Hepatocytes
Cell Culture Techniques
Liver
Fetal Proteins
Messenger RNA
Essential Genes
Green Fluorescent Proteins
Cell Communication
Mental Competency
Albumins
Transcription Factors
Phenotype
Gene Expression

ASJC Scopus subject areas

  • Surgery

Cite this

Fair, J., Cairns, B. A., LaPaglia, M., Wang, J., Meyer, A. A., Kim, H., ... Pevny, L. (2003). Induction of hepatic differentiation in embryonic stem cells by co-culture with embryonic cardiac mesoderm. Surgery, 134(2), 189-196. https://doi.org/10.1067/msy.2003.225

Induction of hepatic differentiation in embryonic stem cells by co-culture with embryonic cardiac mesoderm. / Fair, Jeffrey; Cairns, Bruce A.; LaPaglia, Michael; Wang, Jian; Meyer, Anthony A.; Kim, Hyung; Hatada, Seigo; Smithies, Oliver; Pevny, Larysa.

In: Surgery, Vol. 134, No. 2, 01.08.2003, p. 189-196.

Research output: Contribution to journalArticle

Fair, J, Cairns, BA, LaPaglia, M, Wang, J, Meyer, AA, Kim, H, Hatada, S, Smithies, O & Pevny, L 2003, 'Induction of hepatic differentiation in embryonic stem cells by co-culture with embryonic cardiac mesoderm', Surgery, vol. 134, no. 2, pp. 189-196. https://doi.org/10.1067/msy.2003.225
Fair, Jeffrey ; Cairns, Bruce A. ; LaPaglia, Michael ; Wang, Jian ; Meyer, Anthony A. ; Kim, Hyung ; Hatada, Seigo ; Smithies, Oliver ; Pevny, Larysa. / Induction of hepatic differentiation in embryonic stem cells by co-culture with embryonic cardiac mesoderm. In: Surgery. 2003 ; Vol. 134, No. 2. pp. 189-196.
@article{16322a9c4fea41c8adde5b570bdd0cc7,
title = "Induction of hepatic differentiation in embryonic stem cells by co-culture with embryonic cardiac mesoderm",
abstract = "Background. Modifications in vitro have been used to direct embryonic stem (ES) cells toward endodermal phenotypes including hepatocytes; however, developmental correlates and evidence of biologic activity is lacking, and critical cell-cell interactions have not been investigated. In this study, we hypothesized that cardiac raesoderra (CM) signals ES cells in co-culture to undergo differentiation toward early hepatocyte lineage as determined by morphology and induction of genes essential for endodermal competence and hepatocyte development. Methods. Green fluorescent protein ES derived from A129 mice were cultured with or without embryonic chick cardiac mesoderm. Cultures from day 1, 2, and 4 were analyzed for colony formation and ES morphology and 106 ES-derived cells were isolated for mRNA analysis. Results. ES in co-culture with CM displayed colony formation, polymorphic appearance, and definitive interface with CM. In addition, ES + CM co-culture activated crucial transcription factors (sox 17α, HNF3β, and GATA 4) required for hepatocyte development by day 1. mRNA for albumin and especially α-fetoprotein were also increased by culture days 2 and 4. Conclusions. ES cells co-cultured with CM display morphology and gene expression pattern required for hepatocyte differentiation and appear to recapitulate the molecular events of hepatogenesis.",
author = "Jeffrey Fair and Cairns, {Bruce A.} and Michael LaPaglia and Jian Wang and Meyer, {Anthony A.} and Hyung Kim and Seigo Hatada and Oliver Smithies and Larysa Pevny",
year = "2003",
month = "8",
day = "1",
doi = "10.1067/msy.2003.225",
language = "English (US)",
volume = "134",
pages = "189--196",
journal = "Surgery",
issn = "0039-6060",
publisher = "Mosby Inc.",
number = "2",

}

TY - JOUR

T1 - Induction of hepatic differentiation in embryonic stem cells by co-culture with embryonic cardiac mesoderm

AU - Fair, Jeffrey

AU - Cairns, Bruce A.

AU - LaPaglia, Michael

AU - Wang, Jian

AU - Meyer, Anthony A.

AU - Kim, Hyung

AU - Hatada, Seigo

AU - Smithies, Oliver

AU - Pevny, Larysa

PY - 2003/8/1

Y1 - 2003/8/1

N2 - Background. Modifications in vitro have been used to direct embryonic stem (ES) cells toward endodermal phenotypes including hepatocytes; however, developmental correlates and evidence of biologic activity is lacking, and critical cell-cell interactions have not been investigated. In this study, we hypothesized that cardiac raesoderra (CM) signals ES cells in co-culture to undergo differentiation toward early hepatocyte lineage as determined by morphology and induction of genes essential for endodermal competence and hepatocyte development. Methods. Green fluorescent protein ES derived from A129 mice were cultured with or without embryonic chick cardiac mesoderm. Cultures from day 1, 2, and 4 were analyzed for colony formation and ES morphology and 106 ES-derived cells were isolated for mRNA analysis. Results. ES in co-culture with CM displayed colony formation, polymorphic appearance, and definitive interface with CM. In addition, ES + CM co-culture activated crucial transcription factors (sox 17α, HNF3β, and GATA 4) required for hepatocyte development by day 1. mRNA for albumin and especially α-fetoprotein were also increased by culture days 2 and 4. Conclusions. ES cells co-cultured with CM display morphology and gene expression pattern required for hepatocyte differentiation and appear to recapitulate the molecular events of hepatogenesis.

AB - Background. Modifications in vitro have been used to direct embryonic stem (ES) cells toward endodermal phenotypes including hepatocytes; however, developmental correlates and evidence of biologic activity is lacking, and critical cell-cell interactions have not been investigated. In this study, we hypothesized that cardiac raesoderra (CM) signals ES cells in co-culture to undergo differentiation toward early hepatocyte lineage as determined by morphology and induction of genes essential for endodermal competence and hepatocyte development. Methods. Green fluorescent protein ES derived from A129 mice were cultured with or without embryonic chick cardiac mesoderm. Cultures from day 1, 2, and 4 were analyzed for colony formation and ES morphology and 106 ES-derived cells were isolated for mRNA analysis. Results. ES in co-culture with CM displayed colony formation, polymorphic appearance, and definitive interface with CM. In addition, ES + CM co-culture activated crucial transcription factors (sox 17α, HNF3β, and GATA 4) required for hepatocyte development by day 1. mRNA for albumin and especially α-fetoprotein were also increased by culture days 2 and 4. Conclusions. ES cells co-cultured with CM display morphology and gene expression pattern required for hepatocyte differentiation and appear to recapitulate the molecular events of hepatogenesis.

UR - http://www.scopus.com/inward/record.url?scp=0041326652&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0041326652&partnerID=8YFLogxK

U2 - 10.1067/msy.2003.225

DO - 10.1067/msy.2003.225

M3 - Article

C2 - 12947317

AN - SCOPUS:0041326652

VL - 134

SP - 189

EP - 196

JO - Surgery

JF - Surgery

SN - 0039-6060

IS - 2

ER -