Aspartate Is Limiting for Hematopoietic Stem Cell Function in vivo

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dc.contributor.advisorXu, Jianen
dc.contributor.committeeMemberMorrison, Sean J.en
dc.contributor.committeeMemberHill, Joseph A.en
dc.contributor.committeeMemberThomas, Philip J.en
dc.creatorQi, Leen
dc.creator.orcid0000-0003-4832-2271
dc.date.accessioned2023-09-14T22:29:15Z
dc.date.available2023-09-14T22:29:15Z
dc.date.created2021-08
dc.date.issuedAugust 2021
dc.date.submittedAugust 2021
dc.date.updated2023-09-14T22:29:16Z
dc.description.abstractA key function of the electron transport chain is to promote aspartate synthesis, which is required for cancer cell proliferation. However, it is unclear whether aspartate is also limiting in normal stem cells, which divide intermittently. We found that hematopoietic stem cells (HSCs) do not take up exogenous aspartate. To test if aspartate limits HSC function, we over-expressed the glutamate/aspartate transporter, Glast, or deleted glutamic-oxaloacetic transaminase 1 (Got1). Each increased aspartate levels in hematopoietic stem/progenitor cells, increasing the function of HSCs but not colony-forming progenitors. Conversely, deletion of glutamic-oxaloacetic transaminase 2 (Got2) reduced aspartate levels and HSC function but not colony-forming progenitors. Isotope tracing showed aspartate was used to synthesize asparagine and purines. Both contributed to increased HSC function as deletion of asparagine synthetase (Asns) or treatment with 6-mercaptopurine attenuated the increased function of GLAST over-expressing HSCs. Stem cell function is thus limited by aspartate in some contexts.en
dc.format.mimetypeapplication/pdfen
dc.identifier.urihttps://hdl.handle.net/2152.5/10202
dc.language.isoenen
dc.subjectAspartic Aciden
dc.subjectHematopoietic Stem Cellsen
dc.titleAspartate Is Limiting for Hematopoietic Stem Cell Function in vivoen
dc.typeThesisen
dc.type.materialtexten
thesis.degree.departmentGraduate School of Biomedical Sciencesen
thesis.degree.disciplineCancer Biologyen
thesis.degree.grantorUT Southwestern Medical Centeren
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen

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