27 August 2024

The HMGA2 gene is a promising target for developing treatments to tackle stress-induced blood disorders, researchers have reported.

Exposure to infections or chemotherapy can cause rapid decline in blood cells. Haematopoietic stem cells help the body recover from these stress-induced blood disorders, by proliferating and differentiating into specialist blood cells. However, the exact mechanism of how this occurs is not clear.

The HMGA2 gene was already known to be active in promoting the self-renewal of foetal haematopoietic stem cells, the Japanese researchers say, activating gene expression by modifying chromatin structure. The team decided to further investigate the role of HMGA2 under stress conditions.

Reporting in the EMBO Journal, they describe a laboratory mouse study which showed that overexpression of the gene significantly accelerates the recovery of blood production and haematopoietic stem cells under stress. When HMGA2 was inactivated, the number of stem cells and platelet precursors reduced.

The researchers say the findings have “promising potential” to develop therapies for rapid restoration of blood cell production in patients suffering from severe infections or the effects of cancer treatment.

Researcher Professor Goro Sashida, from Kumamoto University's International Research Centre for Medical Sciences, said: “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.”

Source:

Kubota S, Sun Y, Morii M, Bai J, Ideue T, Hirayama M, Sorin S, Eerdunduleng, Yokomizo-Nakano T, Osato M, Hamashima A, Iimori M, Araki K, Umemoto T, Sashida G. (2024) “Chromatin modifier Hmga2 promotes adult hematopoietic stem cell function and blood regeneration in stress conditions.” EMBO Journal, 29 May 2024, doi: 10.1038/s44318-024-00122-4.

Link: https://www.embopress.org/doi/full/10.1038/s44318-024-00122-4

 

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