Lyssiotis Lab
@lyssiotislab.bsky.social
Cancer and Immune Metabolism Research Laboratory, University of Michigan
Reposted by Lyssiotis Lab
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October 15, 2025 at 12:22 PM
🔗 Check out the full preprint for details & beautiful figures:
www.biorxiv.org/content/10.1...
👏 Congrats to Narges and teams!
🙏 To our awesome collaborators!
cc: @UMPhysiology
www.biorxiv.org/content/10.1...
👏 Congrats to Narges and teams!
🙏 To our awesome collaborators!
cc: @UMPhysiology
https://biorxiv.org/content/10.110…
September 25, 2025 at 1:14 PM
🔗 Check out the full preprint for details & beautiful figures:
www.biorxiv.org/content/10.1...
👏 Congrats to Narges and teams!
🙏 To our awesome collaborators!
cc: @UMPhysiology
www.biorxiv.org/content/10.1...
👏 Congrats to Narges and teams!
🙏 To our awesome collaborators!
cc: @UMPhysiology
10/ Key message
Aspartate aminotransferases (GOT1 & GOT2) are essential for red cell development—primarily through their link to chromatin modification (epigenetic regulation), not just metabolism or aspartate pools!
Aspartate aminotransferases (GOT1 & GOT2) are essential for red cell development—primarily through their link to chromatin modification (epigenetic regulation), not just metabolism or aspartate pools!
September 25, 2025 at 1:14 PM
10/ Key message
Aspartate aminotransferases (GOT1 & GOT2) are essential for red cell development—primarily through their link to chromatin modification (epigenetic regulation), not just metabolism or aspartate pools!
Aspartate aminotransferases (GOT1 & GOT2) are essential for red cell development—primarily through their link to chromatin modification (epigenetic regulation), not just metabolism or aspartate pools!
9/ Human cell relevance
In primary human blood progenitors, knocking out GOT1/2 also blocked RBC formation & increased cell death, mirroring mouse results.
In primary human blood progenitors, knocking out GOT1/2 also blocked RBC formation & increased cell death, mirroring mouse results.
September 25, 2025 at 1:14 PM
9/ Human cell relevance
In primary human blood progenitors, knocking out GOT1/2 also blocked RBC formation & increased cell death, mirroring mouse results.
In primary human blood progenitors, knocking out GOT1/2 also blocked RBC formation & increased cell death, mirroring mouse results.
8/ Clue: Epigenetics! 🧬
GOT1/2 deletion caused abnormal chromatin histone methylation in erythroid cells, suggesting an epigenetic block to development. Loss of GOT1/2 activates apoptosis & cell cycle arrest genes.
GOT1/2 deletion caused abnormal chromatin histone methylation in erythroid cells, suggesting an epigenetic block to development. Loss of GOT1/2 activates apoptosis & cell cycle arrest genes.
September 25, 2025 at 1:14 PM
8/ Clue: Epigenetics! 🧬
GOT1/2 deletion caused abnormal chromatin histone methylation in erythroid cells, suggesting an epigenetic block to development. Loss of GOT1/2 activates apoptosis & cell cycle arrest genes.
GOT1/2 deletion caused abnormal chromatin histone methylation in erythroid cells, suggesting an epigenetic block to development. Loss of GOT1/2 activates apoptosis & cell cycle arrest genes.
7/ Bringing in a tissue-specific, LbNOX mouse model, we then demonstrated that correcting NADH reductive stress didn’t rescue the anemia. So MAS/redox was not the mechanism!
September 25, 2025 at 1:14 PM
7/ Bringing in a tissue-specific, LbNOX mouse model, we then demonstrated that correcting NADH reductive stress didn’t rescue the anemia. So MAS/redox was not the mechanism!
6/ Is it about redox? 🔴⚫
GOT1/2 are part of the malate-aspartate shuttle (MAS), which balances NAD+ and NADH. But deleting another MAS enzyme, MDH1, didn't cause anemia. 🤔
GOT1/2 are part of the malate-aspartate shuttle (MAS), which balances NAD+ and NADH. But deleting another MAS enzyme, MDH1, didn't cause anemia. 🤔
September 25, 2025 at 1:14 PM
6/ Is it about redox? 🔴⚫
GOT1/2 are part of the malate-aspartate shuttle (MAS), which balances NAD+ and NADH. But deleting another MAS enzyme, MDH1, didn't cause anemia. 🤔
GOT1/2 are part of the malate-aspartate shuttle (MAS), which balances NAD+ and NADH. But deleting another MAS enzyme, MDH1, didn't cause anemia. 🤔
5/ Got1 vs. Got2
Surprisingly, Got1 or Got2 loss both caused anemia, but altered aspartate in opposite directions:
GOT2 loss: ↓ aspartate
GOT1 loss: ↑ aspartate
Both led to a block in red blood cell maturation—so, not just about aspartate levels!
Surprisingly, Got1 or Got2 loss both caused anemia, but altered aspartate in opposite directions:
GOT2 loss: ↓ aspartate
GOT1 loss: ↑ aspartate
Both led to a block in red blood cell maturation—so, not just about aspartate levels!
September 25, 2025 at 1:14 PM
5/ Got1 vs. Got2
Surprisingly, Got1 or Got2 loss both caused anemia, but altered aspartate in opposite directions:
GOT2 loss: ↓ aspartate
GOT1 loss: ↑ aspartate
Both led to a block in red blood cell maturation—so, not just about aspartate levels!
Surprisingly, Got1 or Got2 loss both caused anemia, but altered aspartate in opposite directions:
GOT2 loss: ↓ aspartate
GOT1 loss: ↑ aspartate
Both led to a block in red blood cell maturation—so, not just about aspartate levels!
4/ Approach
Narges, et al. deleted GOT1 or GOT2 globally or in erythroid cells in mice. Loss of either enzyme — or both — led to anemia and blocked red cell development at early progenitor stages.
Narges, et al. deleted GOT1 or GOT2 globally or in erythroid cells in mice. Loss of either enzyme — or both — led to anemia and blocked red cell development at early progenitor stages.
September 25, 2025 at 1:14 PM
4/ Approach
Narges, et al. deleted GOT1 or GOT2 globally or in erythroid cells in mice. Loss of either enzyme — or both — led to anemia and blocked red cell development at early progenitor stages.
Narges, et al. deleted GOT1 or GOT2 globally or in erythroid cells in mice. Loss of either enzyme — or both — led to anemia and blocked red cell development at early progenitor stages.
3/ Background
RBCs are constantly replenished (~200B/day), but the metabolic needs of this process are unclear. Profiling shows: Aspartate rises during erythropoiesis. Does aspartate metabolism drive red cell formation? 🤔
RBCs are constantly replenished (~200B/day), but the metabolic needs of this process are unclear. Profiling shows: Aspartate rises during erythropoiesis. Does aspartate metabolism drive red cell formation? 🤔
September 25, 2025 at 1:14 PM
3/ Background
RBCs are constantly replenished (~200B/day), but the metabolic needs of this process are unclear. Profiling shows: Aspartate rises during erythropoiesis. Does aspartate metabolism drive red cell formation? 🤔
RBCs are constantly replenished (~200B/day), but the metabolic needs of this process are unclear. Profiling shows: Aspartate rises during erythropoiesis. Does aspartate metabolism drive red cell formation? 🤔
2/ Working with the @YatrikShahLab and Khoriaty labs, Narges discovered a previously unrecognized, critical role for aspartate aminotransferases (GOT1 & GOT2) in red blood cell (RBC) production, with implications for anemia therapy.
September 25, 2025 at 1:14 PM
2/ Working with the @YatrikShahLab and Khoriaty labs, Narges discovered a previously unrecognized, critical role for aspartate aminotransferases (GOT1 & GOT2) in red blood cell (RBC) production, with implications for anemia therapy.
Thanks for the hype! 🙏🏼
September 5, 2025 at 3:02 PM
Thanks for the hype! 🙏🏼