{"id":{"repo_id":"penn","oai_identifier":"oai:repository.upenn.edu:20.500.14332/60040"},"canonical_url":"https://search.dev.ndltd.org/etd/penn/oai:repository.upenn.edu:20.500.14332/60040","repository":{"repo_id":"penn","name":"University of Pennsylvania","base_url":"https://repository.upenn.edu/server/oai/request"},"display":{"title":"Single-cell NAD(H) levels predict clonal lymphocyte expansion dynamics","abstract":"Adaptive immunity requires the expansion of high affinity lymphocytes from a heterogenous pool. While current models explain this through signal transduction, we hypothesized that antigen affinity tunes discrete metabolic pathways to license clonal lymphocyte dynamics. Herein we identify NAD biosynthesis as a biochemical hub for the TCR affinity-dependent metabolome. Through its’ central anabolic role, NAD biosynthesis governs a quiescence exit checkpoint, pacing proliferation. Normalizing cellular NAD(H) likewise normalizes proliferation across affinities and enhancing NAD biosynthesis permits expansion of lower affinity clones. Furthermore, single-cell differences in NAD(H) predict division potential for both T- and B-cells, prior to the first division, unmixing proliferative heterogeneity. We believe this supports a broader paradigm in which complex signaling networks converge on metabolic pathways to control single-cell behavior.","abstract_html":"Adaptive immunity requires the expansion of high affinity lymphocytes from a heterogenous pool. While current models explain this through signal transduction, we hypothesized that antigen affinity tunes discrete metabolic pathways to license clonal lymphocyte dynamics. Herein we identify NAD biosynthesis as a biochemical hub for the TCR affinity-dependent metabolome. Through its’ central anabolic role, NAD biosynthesis governs a quiescence exit checkpoint, pacing proliferation. Normalizing cellular NAD(H) likewise normalizes proliferation across affinities and enhancing NAD biosynthesis permits expansion of lower affinity clones. Furthermore, single-cell differences in NAD(H) predict division potential for both T- and B-cells, prior to the first division, unmixing proliferative heterogeneity. We believe this supports a broader paradigm in which complex signaling networks converge on metabolic pathways to control single-cell behavior.","abstract_has_math":false,"creators":["Turner, Lucien, Harris"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Bailis, Will"],"committee_chairs":[],"committee_members":[],"year":2024,"date_issued":"2024","date_published":"2024","updated_at":"2026-07-24T03:47:51Z","subjects":["Immunology and Infectious Disease"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://repository.upenn.edu/handle/20.500.14332/60040","outbound_label":"Repository record","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Bailis, Will"]},{"key":"dc:creator","label":"Author","values":["Turner, Lucien, Harris"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2024-06-18T14:16:21Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2024-06-18T14:16:21Z"]},{"key":"dc:date.issued","label":"Date","values":["2024"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation/Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Immunology and Infectious Disease"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://repository.upenn.edu/handle/20.500.14332/60040"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Adaptive immunity requires the expansion of high affinity lymphocytes from a heterogenous pool. While current models explain this through signal transduction, we hypothesized that antigen affinity tunes discrete metabolic pathways to license clonal lymphocyte dynamics. Herein we identify NAD biosynthesis as a biochemical hub for the TCR affinity-dependent metabolome. Through its’ central anabolic role, NAD biosynthesis governs a quiescence exit checkpoint, pacing proliferation. Normalizing cellular NAD(H) likewise normalizes proliferation across affinities and enhancing NAD biosynthesis permits expansion of lower affinity clones. Furthermore, single-cell differences in NAD(H) predict division potential for both T- and B-cells, prior to the first division, unmixing proliferative heterogeneity. We believe this supports a broader paradigm in which complex signaling networks converge on metabolic pathways to control single-cell behavior."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Doctor of Philosophy (PhD)"]},{"key":"dc:title","label":"Title","values":["Single-cell NAD(H) levels predict clonal lymphocyte expansion dynamics"]}]}],"canonical_facts":{"dc:contributor.advisor":["Bailis, Will"],"dc:creator":["Turner, Lucien, Harris"],"dc:date.accessioned":["2024-06-18T14:16:21Z"],"dc:date.available":["2024-06-18T14:16:21Z"],"dc:date.issued":["2024"],"dc:description.abstract":["Adaptive immunity requires the expansion of high affinity lymphocytes from a heterogenous pool. While current models explain this through signal transduction, we hypothesized that antigen affinity tunes discrete metabolic pathways to license clonal lymphocyte dynamics. Herein we identify NAD biosynthesis as a biochemical hub for the TCR affinity-dependent metabolome. Through its’ central anabolic role, NAD biosynthesis governs a quiescence exit checkpoint, pacing proliferation. Normalizing cellular NAD(H) likewise normalizes proliferation across affinities and enhancing NAD biosynthesis permits expansion of lower affinity clones. Furthermore, single-cell differences in NAD(H) predict division potential for both T- and B-cells, prior to the first division, unmixing proliferative heterogeneity. We believe this supports a broader paradigm in which complex signaling networks converge on metabolic pathways to control single-cell behavior."],"dc:description.degree":["Doctor of Philosophy (PhD)"],"dc:identifier.uri":["https://repository.upenn.edu/handle/20.500.14332/60040"],"dc:language.iso":["en"],"dc:subject":["Immunology and Infectious Disease"],"dc:title":["Single-cell NAD(H) levels predict clonal lymphocyte expansion dynamics"],"dc:type":["Dissertation/Thesis"]},"updated_at":"2026-07-24T03:47:51Z"}