Unveiling the Secret of Blood Regeneration: New Insights into Stress Responses in Hematopoietic Stem Cells (HSC)
Kumamoto University researchers have made a groundbreaking discovery that sheds light on how the HMGA2 gene—an essential transcriptional activator involved in chromatin modification—regulates stress responses in hematopoietic stem cells (HSCs), thereby enhancing blood cell production recovery.Exposure to infections or treatments such as chemotherapy often leads to a rapid decline in blood cells, including red blood cells and platelets. HSCs, which reside in the bone marrow that can develop into various types of blood cells, are crucial for recovering from these stress-induced blood disorders. Under stressed conditions, these stem cells proliferate and differentiate to produce blood cells. However, the exact mechanisms of this process have remained unclear.
![](/media//files/2024/08/28/presentation-061924_page-0001.jpg)
CHROMATIN MODIFIER HMGA2 PROMOTES ADULT HEMATOPOIETIC STEM CELL FUNCTION AND BLOOD REGENERATION IN STRESS CONDITIONS
Using conditional knock-in (cKI) and knock-out (KO) mice, the researchers analyzed HMGA2's role in HSC function under both normal and stress conditions, such as exposure to chemotherapy and inflammatory cytokines. They found that overexpression of HMGA2 significantly accelerates the recovery of HSCs and blood production under stress. Conversely, HMGA2 KO mice showed a reduced number of HSCs and platelet precursor cells.
Professor Sashida explained the findings: “Our studies reveal that HMGA2 interacts with chromatin in response to inflammatory cytokines. It is phosphorylated by casein kinase 2 (CK2), which promotes its binding to chromatin and suppresses inflammation-related transcription factors, thereby modulating the inflammatory response.”
This discovery not only enhances our understanding of blood cell regeneration mechanisms but also holds promising potential for developing therapies to rapidly restore blood cell production in individuals suffering from severe infections or post-cancer treatment blood disorders.
Reference
Authors |
Sho Kubota, Yuqi Sun, Mariko Morii, Jie Bai, Takako Ideue, Mayumi Hirayama, Supannika Sorin, Eerdunduleng, Takako Yokomizo-Nakano, Motomi Osato, Ai Hamashima, Mihoko Iimori, Kimi Araki, Terumasa Umemoto & Goro Sashida |
Title of original paper |
Chromatin modifier Hmga2 promotes adult hematopoietic stem cell function and blood regeneration in stress conditions |
Journal | THE EMBO JOURNAL |
DOI | 10.1038/s44318-024-00122-4 |