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Updated: Jun 29, 2025

Derivation of Mouse Trophoblast Stem Cells from Blastocysts
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Derivation of Mouse Trophoblast Stem Cells from Blastocysts

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SP6 controls human cytotrophoblast fate decisions and trophoblast stem cell establishment by targeting MSX2

Yanglin Chen1, Xianhua Ye1, Yulong Zhong1

  • 1Guangdong Provincial Key Laboratory of Bone and Joint Degenerative Diseases, Department of Physiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.

Developmental Cell
|April 6, 2024
PubMed

The commitment and differentiation of human placental progenitor cytotrophoblast (CT) cells are crucial for a successful pregnancy, but the underlying mechanism remains poorly understood. Here, we identified the transcription factor (TF), specificity protein 6 (SP6), as a human species-specific trophoblast lineage TF expressed in human placental CT cells. Using pluripotent stem cells as a model, we demonstrated that SP6 controls CT generation and the establishment of trophoblast stem cells (TSCs) and identified msh homeobox 2 (MSX2) as the downstream effector in these events. Mechanistically, we showed that SP6 interacts with histone acetyltransferase P300 to alter the landscape of H3K27ac at targeted regulatory elements, thereby favoring transcriptional activation and facilitating CT cell fate decisions and TSC maintenance. Our results established SP6 as a regulator of the human trophoblast lineage and implied its role in placental development and the pathogenies of placental diseases.

Keywords:
MSX2cytotrophoblast fate decisionhuman species-specificplacental progenitorspecificity protein 6transcription factortrophoblast lineagetrophoblast stem cell

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