Shintaro Watanuki, Hiroshi Kobayashi, Yuki Sugiura, Masamichi Yamamoto, Daiki Karigane, Kohei Shiroshita, Yuriko Sorimachi, Shinya Fujita, Takayuki Morikawa, Shuhei Koide, Motohiko Oshima, Akira Nishiyama, Koichi Murakami, Miho Haraguchi, Shinpei Tamaki, Takehiro Yamamoto, Tomohiro Yabushita, Yosuke Tanaka, Go Nagamatsu, Hiroaki Honda, Shinichiro Okamoto, Nobuhito Goda, Tomohiko Tamura, Ayako Nakamura-Ishizu, Makoto Suematsu, Atsushi Iwama, Toshio Suda, Keiyo Takubo
Metabolic pathways are plastic and rapidly change in response to stress or perturbation. Current metabolic profiling techniques require lysis of many cells, complicating the tracking of metabolic changes over time after stress in rare cells such as hematopoietic stem cells (HSCs). Here, we aimed to identify the key metabolic enzymes that define differences in glycolytic metabolism between steady-state and stress conditions in murine HSCs and elucidate their regulatory mechanisms. Through quantitative 13 C metabolic flux analysis of glucose metabolism using high-sensitivity glucose tracing and mathematical modeling, we found that HSCs activate the glycolytic rate-limiting enzyme phosphofructokinase (PFK) during proliferation and oxidative phosphorylation (OXPHOS) inhibition...
April 4, 2024: ELife