Project description: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. Collectively, our findings suggest an essential role for Myh9 in the survival and maintenance of HSPC in normal hematopoiesis.

2022-06-01 | GSE198134 | GEO

Single-cell telomere-length quantification couples telomere length to meristem activity and stem cell development in Arabidopsis.

Project description: Not available

| S-EPMC4827700 | biostudies-literature

Reconstructing the in vivo dynamics of hematopoietic stem cells from telomere length distributions.

Project description: Not available

| S-EPMC4744200 | biostudies-literature

Association between donor leukocyte telomere length and survival after unrelated allogeneic hematopoietic cell transplantation for severe aplastic anemia.

Project description: Not available

| S-EPMC4388056 | biostudies-literature

Ligase4 is essential for hematopoietic stem cell maintenance

Project description:Hematopoietic stem cells (HSCs) maintain the blood system during steady state and in response to stress. As a result, the accumulation of DNA damage has been proposed as a principal factor that contributes to the functional decline in HSC renewal during aging and stress. However, how the HSCs are sustained in the face of increased DNA damage remains unknown. Here, we address this question by studying the role of non-homologous end joining (NHEJ) in HSC. Using a mouse model of a naturally occurring human hypomorphic Lig4 mutation, we show a definitive effect on the steady state of activated HSCs. This population is severely diminished in the Lig4 mutant mice from the loss of selfrenewing HSCs. Our data suggests that defective NHEJ resulting from this Lig4 mutation depletes only the cycling HSCs but not the dormant HSCs, demonstrating that Lig4 is required for maintaining HSC by preserving their cycling pool.

2016-12-31 | GSE65195 | GEO

Effect of Recipient Age and Stem Cell Source on the Association between Donor Telomere Length and Survival after Allogeneic Unrelated Hematopoietic Cell Transplantation for Severe Aplastic Anemia.

Project description: Not available

| S-EPMC5116252 | biostudies-literature