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Updated: Jan 26, 2026

Generation and Expansion of Human Cardiomyocytes from Patient Peripheral Blood Mononuclear Cells
Published on: February 12, 2021
Essential role of NONO-HOXA1-Wnt axis in cardiomyocyte differentiation
Zhiyu Feng1, Yuan Gao1, Han Gao1
1Shanghai Key Laboratory of Birth Defects, Pediatric Heart Center, Children's Hospital of Fudan University, Shanghai, China.
Abstract:
NONO is recognized as a critical molecular scaffold involved in both transcriptional and posttranscriptional regulation. Mutations in NONO are frequently linked to congenital heart diseases (CHDs) in humans. However, the mechanisms by which NONO regulates cardiac development remain elusive. Here, we identified NONO as a pivotal dual-function regulator of cardiomyocyte differentiation in human induced pluripotent stem cells (hiPSCs). NONO deficiency in hiPSCs results in a distinct defect in early cardiomyocyte differentiation. Mechanistically, NONO interacts with HOXA1 and regulates the dynamic expression of key genes during early cardiomyocyte differentiation. ChIP-seq analysis reveals that NONO loss reduces HOXA1 occupancy at target genes, compromising its transcriptional regulation. Additionally, NONO and HOXA1 cooperatively activate the Wnt signaling. Taken together, these findings establish the NONO-HOXA1-Wnt axis as a key molecular mechanism in cardiomyocyte differentiation and provide insights into the etiology of CHDs associated with NONO mutations.
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