Myh9 Plays an Essential Role in the Survival and Maintenance of Hematopoietic Stem/Progenitor Cells

Abstract

Myosin heavy chain 9 (MYH9) gene encodes a protein named non-muscle heavy chain IIA (NMHC IIA), interacting with actin and participating in various biological processes. Mutations in MYH9 cause an array of autosomal dominant disorders, known as MYH9-related diseases (MYH9-RD). However, the role of MYH9 in normal hematopoiesis remains largely unexplored. By using Mx1-cre Myh9 conditional knockout mice, we established an inducible system to precisely inactivate Myh9 function in hematopoietic cells in vivo. The results showed that deletion of Myh9 led to severe defects in hematopoiesis, characterized by pancytopenia, drastic decreases of hematopoietic stem/progenitor cells (HSPC), and bone marrow failure, causing early lethality in mice. The defect in hematopoiesis caused by Myh9 ablation is cell autonomous. In addition, Myh9 deletion impairs HSPC repopulation capacity and increases apoptosis. RNA sequencing results revealed significant alterations in the expression of genes related to HSC self-renewal and maintenance, while multiple signal pathways were also involved, including genes for HSC and myeloid cell development, intrinsic apoptosis, targets of mTOR signaling, and maturity of hematopoietic cells. Our present study suggests an essential role for Myh9 in the survival and maintenance of HSPC in normal hematopoiesis.

Targeting MYH9 represses USP14-mediated NAP1L1 deubiquitination and enhances temozolomide response in Glioma

“…Myosin heavy chain 9 (MYH9), part of the myosin family, participates in cell adhesion, polarity, motility and migration [4]. MYH9 is a skeletal protein and plays a critical role in multiple human diseases [5][6][7][8][9].…”

“…Myosin heavy chain 9 (MYH9), part of the myosin family, participates in cell adhesion, polarity, motility and migration [4]. MYH9 is a skeletal protein and plays a critical role in many human diseases [5][6][7][8][9]. Over the past several years, more and more studies have shown that MYH9 is increased in many cancers, such as non-small cell lung cancer [10], colorectal cancer [11], prostate cancer [12], diffuse large B-cell lymphoma [13], renal cell carcinoma [14], glioma [15] and hepatocellular carcinoma [16].…”

Quercetin promotes the proliferation and maturation of NK cells by binding to MYH9 and improves cognitive functions in aged mice

“…5G), which revealed an association between quercetin and the MYH9 protein. The MYH9 protein, a fundamental constituent of the cellular skeleton, plays a critical role in preserving and facilitating the functionality of HSCs [37]. Additionally, it exerts in uence over immune cells and regulates the cytotoxicity of NK cells [38].…”

Drug-tolerant persister B-cell precursor acute lymphoblastic leukemia cells

“…MYH9 was detected as binding to GSN in a high throughput screen (51). It is needed for survival of HSPC (52), regulates mature B-cell functions (53) and has an important contribution in hematologic malignancies (54)(55)(56).…”