生物
中胚层
细胞生物学
SMAD公司
染色质
外胚层
胚胎干细胞
节点信号
节的
神经外胚层
信号转导
遗传学
胚胎发生
原肠化
胚胎
基因
作者
Cong Zhang,Yongli Shan,Huaisong Lin,Yanqi Zhang,Qi Xing,Jinmin Zhu,Tiancheng Zhou,Lin Ai,Qianyu Chen,Junwei Wang,Guoshun Pan
摘要
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.
科研通智能强力驱动
Strongly Powered by AbleSci AI