Growth characteristics of fibroblasts stably expressing AGAT and GAMT.

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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Bibliographic Details
Main Author: Chloe Wells (17231887) (author)
Other Authors: Jon Sorgenfrei (21273708) (author), Sadie L. Johnson (21273711) (author), Devin Albertson (21273714) (author), Jared Rutter (2128906) (author), Steven Andrew Baker (10150952) (author)
Published: 2025
Subjects:
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
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Summary:<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>

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