Distinct GAGE and MAGE-A expression during early human development indicate specific roles in lineage differentiation
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Distinct GAGE and MAGE-A expression during early human development indicate specific roles in lineage differentiation. / Gjerstorff, Morten F; Harkness, Linda; Kassem, Moustapha; Frandsen, Ulrik; Lutterodt, Melissa; Møllgård, Kjeld; Ditzel, Henrik J.
I: Human Reproduction, Bind 23, Nr. 10, 10.2008, s. 2194-201.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Distinct GAGE and MAGE-A expression during early human development indicate specific roles in lineage differentiation
AU - Gjerstorff, Morten F
AU - Harkness, Linda
AU - Kassem, Moustapha
AU - Frandsen, Ulrik
AU - Lutterodt, Melissa
AU - Møllgård, Kjeld
AU - Ditzel, Henrik J
PY - 2008/10
Y1 - 2008/10
N2 - BACKGROUND: Expression of cancer/testis-associated proteins (CTAs) has traditionally been considered to be restricted to germ cells in normal tissues and to different types of malignancies. We have evaluated the potential role of CTAs in early human development.METHODS: Using immunohistochemistry and RT-PCR, we investigated the expression of CTAs in differentiated human embryonic stem cells (hESC) and in late embryos and early fetuses.RESULTS: We found that melanoma antigen A (MAGE-A) family members were expressed during differentiation of hESC to embryoid bodies and in teratomas, and overlapped with expression of the neuroectodermal markers beta-tubulin 3, Pax6 and nestin. A widespread expression of MAGE-A was also observed in neurons of the early developing central nervous system and peripheral nerves. G antigen (GAGE) expression was present in the early ectoderm of embryos, including cells of the ectodermal ring and apical epidermal ridge. Neuroectodermal cells in the floor plate and adjacent processes and endfeet of radial glial cells also expressed GAGE. In addition, GAGE family members were expressed in the peripheral adrenal cortex of 6-9-week-old embryos and fetuses, which specifically correlated with massive cellular proliferation and establishment of the definitive and fetal zones. Overlapping expression of MAGE-A and GAGE proteins occurred in migrating primordial germ cells.CONCLUSIONS: Our results show that CTAs, in addition to their role in germ cells, may be involved in early development of various types of somatic cells, and suggest that they are implicated in specific differentiation processes.
AB - BACKGROUND: Expression of cancer/testis-associated proteins (CTAs) has traditionally been considered to be restricted to germ cells in normal tissues and to different types of malignancies. We have evaluated the potential role of CTAs in early human development.METHODS: Using immunohistochemistry and RT-PCR, we investigated the expression of CTAs in differentiated human embryonic stem cells (hESC) and in late embryos and early fetuses.RESULTS: We found that melanoma antigen A (MAGE-A) family members were expressed during differentiation of hESC to embryoid bodies and in teratomas, and overlapped with expression of the neuroectodermal markers beta-tubulin 3, Pax6 and nestin. A widespread expression of MAGE-A was also observed in neurons of the early developing central nervous system and peripheral nerves. G antigen (GAGE) expression was present in the early ectoderm of embryos, including cells of the ectodermal ring and apical epidermal ridge. Neuroectodermal cells in the floor plate and adjacent processes and endfeet of radial glial cells also expressed GAGE. In addition, GAGE family members were expressed in the peripheral adrenal cortex of 6-9-week-old embryos and fetuses, which specifically correlated with massive cellular proliferation and establishment of the definitive and fetal zones. Overlapping expression of MAGE-A and GAGE proteins occurred in migrating primordial germ cells.CONCLUSIONS: Our results show that CTAs, in addition to their role in germ cells, may be involved in early development of various types of somatic cells, and suggest that they are implicated in specific differentiation processes.
KW - Adrenal Cortex/embryology
KW - Antigens, Neoplasm/metabolism
KW - Cell Differentiation
KW - Cell Lineage
KW - Cell Movement
KW - Central Nervous System/embryology
KW - Ectoderm/embryology
KW - Embryonic Development
KW - Embryonic Stem Cells/metabolism
KW - Female
KW - Fetal Development
KW - Fetus/metabolism
KW - Germ Cells/metabolism
KW - Humans
KW - Immunohistochemistry
KW - Male
KW - Melanoma-Specific Antigens
KW - Neoplasm Proteins/metabolism
KW - Neural Plate/embryology
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Teratoma/metabolism
U2 - 10.1093/humrep/den262
DO - 10.1093/humrep/den262
M3 - Journal article
C2 - 18611917
VL - 23
SP - 2194
EP - 2201
JO - Human Reproduction
JF - Human Reproduction
SN - 0268-1161
IS - 10
ER -
ID: 203597835