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Effect of a FOXO1 inhibitor on trophoblast differentiation from human pluripotent stem cells and ERV-associated gene expression.
Tanaka, Erika; Koyanagi-Aoi, Michiyo; Nakagawa, So; Shimode, Sayumi; Yamada, Hideto; Terai, Yoshito; Aoi, Takashi.
Afiliación
  • Tanaka E; Division of Stem Cell Medicine, Graduate School of Medicine, Kobe University, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
  • Koyanagi-Aoi M; Division of Advanced Medical Science, Graduate School of Science, Technology and Innovation, Kobe University, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
  • Nakagawa S; Department of Obstetrics and Gynecology, Graduate School of Medicine, Kobe University, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
  • Shimode S; Division of Stem Cell Medicine, Graduate School of Medicine, Kobe University, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
  • Yamada H; Division of Advanced Medical Science, Graduate School of Science, Technology and Innovation, Kobe University, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
  • Terai Y; Center for Human Resource Development for Regenerative Medicine, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
  • Aoi T; Department of Molecular Life Science, Tokai University School of Medicine, 143 Shimokasuya, Isehara, 259-1193, Japan.
Regen Ther ; 26: 729-740, 2024 Jun.
Article en En | MEDLINE | ID: mdl-39290630
ABSTRACT

Introduction:

In human placental development, the trophectoderm (TE) appears in blastocysts on day 5 post-fertilization and develops after implantation into three types of trophoblast lineages cytotrophoblast (CT), syncytiotrophoblast (ST), and extravillous trophoblast (EVT). CDX2/Cdx2 is expressed in the TE, and Cdx2 expression is upregulated by knockdown of Foxo1 in mouse ESCs. However, the significance of FOXO1 in trophoblast lineage differentiation during the early developmental period remains unclear. In this study, we examined the effect of FOXO1 inhibition on the differentiation of naive human induced pluripotent stem cells (iPSCs) into TE and trophoblast lineages.

Methods:

We induced TE differentiation from naive iPSCs in the presence or absence of a FOXO1 inhibitor, and the resulting cells were subjected to trophoblast differentiation procedures without the FOXO1 inhibitor. The cells obtained in these processes were assessed for morphology, gene expression, and hCG secretion using phase-contrast microscopy, reverse transcription polymerase chain reaction (RT-PCR), quantitative RT-PCR (RT-qPCR), RNA-seq, immunochromatography, and a chemiluminescent enzyme immunoassay.

Results:

In the induction of trophoblast differentiation from naive iPSCs, treatment with a FOXO1 inhibitor resulted in the enhanced expression of TE markers, CDX2 and HAND1, but conversely decreased the expression of ST markers, such as ERVW1 (Syncytin-1) and GCM1, and an EVT marker, HLA-G. The proportion of cells positive for an early TE marker TACSTD2 and negative for a late TE marker ENPEP was higher in FOXO1 inhibitor-treated cells than in non-treated cells. The expressions of ERVW1 (Syncytin-1), ERVFRD-1 (Syncytin-2), and other endogenous retrovirus (ERV)-associated genes that have been reported to be expressed in trophoblasts were suppressed in the cells obtained by differentiating the TE cells treated with FOXO1 inhibitor.

Conclusions:

Treatment with a FOXO1 inhibitor during TE induction from naive iPSCs promotes early TE differentiation but hinders the progression of differentiation into ST and EVT. The suppression of ERV-associated genes may be involved in this process.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Regen Ther Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Regen Ther Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Países Bajos