Growth characteristics of fibroblasts stably expressing AGAT and GAMT.
<p>(A) A model depicting the two sources of intracellular creatine. Creatine is either imported via CT1 or synthesized from its amino acid precursors: L-arginine; glycine; and methionine. The latter is converted into SAM via MAT2. Created with BioRender.com. (B) Growth of WT fibroblasts stably...
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2025
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| _version_ | 1852020628567097344 |
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| author | Chloe Wells (17231887) |
| author2 | Jon Sorgenfrei (21273708) Sadie L. Johnson (21273711) Devin Albertson (21273714) Jared Rutter (2128906) Steven Andrew Baker (10150952) |
| author2_role | author author author author author |
| author_facet | Chloe Wells (17231887) Jon Sorgenfrei (21273708) Sadie L. Johnson (21273711) Devin Albertson (21273714) Jared Rutter (2128906) Steven Andrew Baker (10150952) |
| author_role | author |
| dc.creator.none.fl_str_mv | Chloe Wells (17231887) Jon Sorgenfrei (21273708) Sadie L. Johnson (21273711) Devin Albertson (21273714) Jared Rutter (2128906) Steven Andrew Baker (10150952) |
| dc.date.none.fl_str_mv | 2025-05-08T17:50:49Z |
| dc.identifier.none.fl_str_mv | 10.1371/journal.pone.0319350.g007 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/figure/Growth_characteristics_of_fibroblasts_stably_expressing_AGAT_and_GAMT_/28964394 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biochemistry Medicine Cell Biology Genetics Molecular Biology Mental Health target cell types natural cellular compartment highly energetic tissues critical metabolite used affected individuals suffer creatine uptake relies creatine transporter 1 healthy control fibroblasts endogenous creatine synthesis div >< p intracellular creatine concentrations intracellular synthesis transport creatine primary fibroblasts patient fibroblasts intracellular concentration slc6a8 </ selectively expressed protein product proper targeting phenotypes referred linked gene like behaviors intellectual disability hek293t cells genetic defects gene therapy gatm </ function mutations far exceeding effective therapies common set common form |
| dc.title.none.fl_str_mv | Growth characteristics of fibroblasts stably expressing AGAT and GAMT. |
| dc.type.none.fl_str_mv | Image Figure info:eu-repo/semantics/publishedVersion image |
| description | <p>(A) A model depicting the two sources of intracellular creatine. Creatine is either imported via CT1 or synthesized from its amino acid precursors: L-arginine; glycine; and methionine. The latter is converted into SAM via MAT2. Created with BioRender.com. (B) Growth of WT fibroblasts stably expressing the indicated constructs in standard media (DMEM + 15% FBS + P/S). N = 6. Two-sided K-S test n.s. indicates not significant. (C) Growth of CT1 loss-of-function (<i>SLC6A8</i><sup><i>Δex10-11/y</i></sup>) patient fibroblasts stably expressing the indicated constructs in standard media. N = 6. Two-sided K-S test **** indicates <i>P</i> < 0.0001. (D) Similar experiment to (C) except media was supplemented with creatine precursor amino acids to 1 mM above standard media. N = 6. Two-sided K-S test *** indicates <i>P</i> < 0.001. (E) Growth of CT1 loss-of-function (<i>SLC6A8</i><sup><i>W556X/y</i></sup>) patient fibroblasts stably expressing the indicated constructs in standard media. N = 6. Two-sided K-S test * indicates <i>P</i> < 0.05. (F) Similar experiment to (E) except media was supplemented with creatine precursor amino acids. N = 6. Two-sided K-S test **** indicates <i>P</i> < 0.0001. Lines indicate a LOESS curve fit to the mean at each timepoint. Error bars show mean + /- SEM.</p> |
| eu_rights_str_mv | openAccess |
| id | Manara_df06175cfeccd5ae81832fa78e5bf2e2 |
| identifier_str_mv | 10.1371/journal.pone.0319350.g007 |
| network_acronym_str | Manara |
| network_name_str | ManaraRepo |
| oai_identifier_str | oai:figshare.com:article/28964394 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Growth characteristics of fibroblasts stably expressing AGAT and GAMT.Chloe Wells (17231887)Jon Sorgenfrei (21273708)Sadie L. Johnson (21273711)Devin Albertson (21273714)Jared Rutter (2128906)Steven Andrew Baker (10150952)BiochemistryMedicineCell BiologyGeneticsMolecular BiologyMental Healthtarget cell typesnatural cellular compartmenthighly energetic tissuescritical metabolite usedaffected individuals suffercreatine uptake reliescreatine transporter 1healthy control fibroblastsendogenous creatine synthesisdiv >< pintracellular creatine concentrationsintracellular synthesistransport creatineprimary fibroblastspatient fibroblastsintracellular concentrationslc6a8 </selectively expressedprotein productproper targetingphenotypes referredlinked genelike behaviorsintellectual disabilityhek293t cellsgenetic defectsgene therapygatm </function mutationsfar exceedingeffective therapiescommon setcommon form<p>(A) A model depicting the two sources of intracellular creatine. Creatine is either imported via CT1 or synthesized from its amino acid precursors: L-arginine; glycine; and methionine. The latter is converted into SAM via MAT2. Created with BioRender.com. (B) Growth of WT fibroblasts stably expressing the indicated constructs in standard media (DMEM + 15% FBS + P/S). N = 6. Two-sided K-S test n.s. indicates not significant. (C) Growth of CT1 loss-of-function (<i>SLC6A8</i><sup><i>Δex10-11/y</i></sup>) patient fibroblasts stably expressing the indicated constructs in standard media. N = 6. Two-sided K-S test **** indicates <i>P</i> < 0.0001. (D) Similar experiment to (C) except media was supplemented with creatine precursor amino acids to 1 mM above standard media. N = 6. Two-sided K-S test *** indicates <i>P</i> < 0.001. (E) Growth of CT1 loss-of-function (<i>SLC6A8</i><sup><i>W556X/y</i></sup>) patient fibroblasts stably expressing the indicated constructs in standard media. N = 6. Two-sided K-S test * indicates <i>P</i> < 0.05. (F) Similar experiment to (E) except media was supplemented with creatine precursor amino acids. N = 6. Two-sided K-S test **** indicates <i>P</i> < 0.0001. Lines indicate a LOESS curve fit to the mean at each timepoint. Error bars show mean + /- SEM.</p>2025-05-08T17:50:49ZImageFigureinfo:eu-repo/semantics/publishedVersionimage10.1371/journal.pone.0319350.g007https://figshare.com/articles/figure/Growth_characteristics_of_fibroblasts_stably_expressing_AGAT_and_GAMT_/28964394CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/289643942025-05-08T17:50:49Z |
| spellingShingle | Growth characteristics of fibroblasts stably expressing AGAT and GAMT. Chloe Wells (17231887) Biochemistry Medicine Cell Biology Genetics Molecular Biology Mental Health target cell types natural cellular compartment highly energetic tissues critical metabolite used affected individuals suffer creatine uptake relies creatine transporter 1 healthy control fibroblasts endogenous creatine synthesis div >< p intracellular creatine concentrations intracellular synthesis transport creatine primary fibroblasts patient fibroblasts intracellular concentration slc6a8 </ selectively expressed protein product proper targeting phenotypes referred linked gene like behaviors intellectual disability hek293t cells genetic defects gene therapy gatm </ function mutations far exceeding effective therapies common set common form |
| status_str | publishedVersion |
| title | Growth characteristics of fibroblasts stably expressing AGAT and GAMT. |
| title_full | Growth characteristics of fibroblasts stably expressing AGAT and GAMT. |
| title_fullStr | Growth characteristics of fibroblasts stably expressing AGAT and GAMT. |
| title_full_unstemmed | Growth characteristics of fibroblasts stably expressing AGAT and GAMT. |
| title_short | Growth characteristics of fibroblasts stably expressing AGAT and GAMT. |
| title_sort | Growth characteristics of fibroblasts stably expressing AGAT and GAMT. |
| topic | Biochemistry Medicine Cell Biology Genetics Molecular Biology Mental Health target cell types natural cellular compartment highly energetic tissues critical metabolite used affected individuals suffer creatine uptake relies creatine transporter 1 healthy control fibroblasts endogenous creatine synthesis div >< p intracellular creatine concentrations intracellular synthesis transport creatine primary fibroblasts patient fibroblasts intracellular concentration slc6a8 </ selectively expressed protein product proper targeting phenotypes referred linked gene like behaviors intellectual disability hek293t cells genetic defects gene therapy gatm </ function mutations far exceeding effective therapies common set common form |