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- Title
An Improved Protocol for Targeted Differentiation of Primed Human Induced Pluripotent Stem Cells into HLA-G-Expressing Trophoblasts to Enable the Modeling of Placenta-Related Disorders.
- Authors
Shum, Ian O.; Merkert, Sylvia; Malysheva, Svitlana; Jahn, Kirsten; Lachmann, Nico; Verboom, Murielle; Frieling, Helge; Hallensleben, Michael; Martin, Ulrich
- Abstract
Abnormalities at any stage of trophoblast development may result in pregnancy-related complications. Many of these adverse outcomes are discovered later in pregnancy, but the underlying pathomechanisms are constituted during the first trimester. Acquiring developmentally relevant material to elucidate the disease mechanisms is difficult. Human pluripotent stem cell (hPSC) technology can provide a renewable source of relevant cells. BMP4, A83-01, and PD173074 (BAP) treatment drives trophoblast commitment of hPSCs toward syncytiotrophoblast (STB), but lacks extravillous trophoblast (EVT) cells. EVTs mediate key functions during placentation, remodeling of uterine spiral arteries, and maintenance of immunological tolerance. We optimized the protocol for a more efficient generation of HLA-Gpos EVT-like trophoblasts from primed hiPSCs. Increasing the concentrations of A83-01 and PD173074, while decreasing bulk cell density resulted in an increase in HLA-G of up to 71%. Gene expression profiling supports the advancements of our treatment regarding the generation of trophoblast cells. The reported differentiation protocol will allow for an on-demand access to human trophoblast cells enriched for HLA-Gpos EVT-like cells, allowing for the elucidation of placenta-related disorders and investigating the immunological tolerance toward the fetus, overcoming the difficulties in obtaining primary EVTs without the need for a complex differentiation pathway via naïve pluripotent or trophoblast stem cells.
- Subjects
TROPHOBLAST; PLURIPOTENT stem cells; GENE expression profiling; PREGNANCY complications; HUMAN stem cells; UTERINE artery
- Publication
Cells (2073-4409), 2023, Vol 12, Issue 16, p2070
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells12162070