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Updated: Jul 2, 2025

A Simple Method to Identify Kinases That Regulate Embryonic Stem Cell Pluripotency by High-throughput Inhibitor Screening
Published on: May 12, 2017
HBO1 determines SMAD action in pluripotency and mesendoderm specification
Cong Zhang1,2,3, Yongli Shan1,2,3, Huaisong Lin1,2,3
1Key Laboratory of Immune Response and Immunotherapy, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530,China; Guangzhou Medical University, Guangzhou 511436, China.
None:
TGF-β signaling family plays an essential role to regulate fate decisions in pluripotency and lineage specification. How the action of TGF-β family signaling is intrinsically executed remains not fully elucidated. Here, we show that HBO1, a MYST histone acetyltransferase (HAT) is an essential cell intrinsic determinant for TGF-β signaling in human embryonic stem cells (hESCs). HBO1-/- hESCs fail to response to TGF-β signaling to maintain pluripotency and spontaneously differentiate into neuroectoderm. Moreover, HBO1 deficient hESCs show complete defect in mesendoderm specification in BMP4-triggered gastruloids or teratomas. Molecularly, HBO1 interacts with SMAD4 and co-binds the open chromatin labeled by H3K14ac and H3K4me3 in undifferentiated hESCs. Upon differentiation, HBO1/SMAD4 co-bind and maintain the mesoderm genes in BMP4-triggered mesoderm cells while lose chromatin occupancy in neural cells induced by dual-SMAD inhibition. Our data reveal an essential role of HBO1, a chromatin factor to determine the action of SMAD in both human pluripotency and mesendoderm specification.
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