Trophoblast stem cells differentiate in vitro into invasive trophoblast giant cells.

Abstract:

:Trophoblast cells are characterized by an invasive behavior into the surrounding uterine tissue. In rodents, an early peri-/endovascular type of invasion exerted by trophoblast giant cells can be distinguished from a late interstitial type carried out by glycogen trophoblast cells. Analysis of the molecular mechanisms of trophoblast invasion has been hampered, however, by the complex temporal and spatial patterns of invasion. We utilized trophoblast stem (TS) cell lines to study trophoblast invasion in vitro and to establish a model that facilitates investigation of this process on the molecular level. Our results showed that trophoblast giant cells that differentiate from TS cells in vitro are capable of penetrating a reconstituted basement membrane matrix. Consequently, invasion rates were increased in various giant cell differentiation-promoting conditions. We also derived TS cell lines that are homozygous for a mutation of the Hand1 transcription factor. The Hand1-/- TS cells showed reduced levels of giant cell differentiation and exhibited an approximately 50% decrease in invasion rates. In summary, trophoblast giant cells that differentiate from TS cells in vitro recapitulate the invasive capacity of normal trophoblast cells in vivo. The TS cell system is a valuable tool to identify and quantitatively study regulators of trophoblast invasion.

journal_name

Dev Biol

journal_title

Developmental biology

authors

Hemberger M,Hughes M,Cross JC

doi

10.1016/j.ydbio.2004.03.040

subject

Has Abstract

pub_date

2004-07-15 00:00:00

pages

362-71

issue

2

eissn

0012-1606

issn

1095-564X

pii

S0012160604002738

journal_volume

271

pub_type

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