A key regulator of haematopoietic stem cells has been identified, showing a new way in which stem cells control inflammation, researchers have reported.
The study led by US researchers at Memorial Sloan Kettering Cancer Center, New York, NY, and the New York Genome Center found that a gene called SON is a key controller of blood stem cell fate.
The team was led by co-first authors Dr Hanzhi Luo, a postdoctoral fellow at MSK and Dr Mariela Cortés-López, a postdoctoral fellow at the Genome Center and Weill Cornell Medicine.
Writing in Cell Stem Cell, they showed levels of the SON protein decrease when m6A RNA methylation – an RNA modification – is hampered, leading to defects in stem cell commitment and function.
They also found SON plays a role in controlling inflammation by reducing the expression of proinflammatory genes.
The study highlights SON’s role in ZTTK syndrome, a rare genetic disease in which spontaneous mutations in SON lead to brain and blood defects.
Senior study author Dr Michael Kharas, a cancer biologist at MSK’s Sloan Kettering Institute, said: “Our findings also suggest that targeting SON and its downstream program may be a promising strategy for expanding blood stem cell populations.
“Along with providing new insights into the way stem cells control their fate and their role in controlling inflammation, our findings may help understand the impact of cancer treatments that work by inhibiting RNA methylation.”
Luo H, Cortés-López M, Tam CL, Xiao M, Wakiro I, Chu KL, Pierson A, Chan M, Chang K, Yang X, Fecko D, Han G, Ahn EE, Morris QD, Landau DA, Kharas MG. (2023) “SON is an essential m6A target for hematopoietic stem cell fate.” Cell Stem Cell, doi: 10.1016/j.stem.2023.11.006.
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