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ZNF423/Zfp423 is aberrantly upregulated in both human and genetically engineered mouse models (GEMM) of MPNST compared to PNF and normal nerves. (A) Bar plot showing Zfp423 transcript expression (RPKM) across embryonic (E13.5, E17.5) and postnatal (P1, P5, P14, P24, and P60) murine developmental timepoints. (B) Merged tSNE plot generated from scRNAseq data of murine Schwann cells at P1, P5, P14, and P60 showing Zfp423 expression restricted to the immature Schwann cells (iSC) postnatally. The color gradient of grey to red indicates relative transcript abundance of Zfp423 per cell, with grey representing no detectable expression and dark red indicating high expression. Data were obtained from the Sciatic Nerve ATlas (SNAT). Cell populations include: proliferating Schwann cells (prol. SC), immature Schwann cells (iSC), pro-myelinating Schwann cells (pmSCs), transition SCs (tSC), mature non-myelinating SCs (nm(R)SC) and myelinating SCs (mSC). (C) Dot plot comparing log 2 -normalized ZNF423 gene expression between PNF ( n =32), and MPNST ( n =14). P-values represent two-tailed unpaired t-test with Welch’s correction. (D) Dot plot comparing ZNF423 mRNA levels in normal nerve ( n =3), PNF ( n =26), and MPNST ( n =6) (GEO accession: GSE41747). Error bars reflect standard error of the mean (SEM). P-values represent two-tailed unpaired t-test with Welch’s correction. (E) Dot plot depicting log 2 -normalized counts of Zfp423 for each sample ( n =3 per group). Error bars reflect standard error of the mean (SEM). P-values represent unpaired, two-tailed t-test with Welch’s correction. (F) Dot plot depicting log 2 -normalized counts of Zfp423 following CRISPR-mediated knockout of <t>Suz12</t> compared to control ( n =3 per group). Error bars reflect standard error of the mean (SEM). P-values represent two-tailed unpaired t-test with Welch’s correction. ****=p-value≤0.0001, ***=p-value≤0.001, *=p-value≤0.05, ns=not significant.
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ZNF423/Zfp423 is aberrantly upregulated in both human and genetically engineered mouse models (GEMM) of MPNST compared to PNF and normal nerves. (A) Bar plot showing Zfp423 transcript expression (RPKM) across embryonic (E13.5, E17.5) and postnatal (P1, P5, P14, P24, and P60) murine developmental timepoints. (B) Merged tSNE plot generated from scRNAseq data of murine Schwann cells at P1, P5, P14, and P60 showing Zfp423 expression restricted to the immature Schwann cells (iSC) postnatally. The color gradient of grey to red indicates relative transcript abundance of Zfp423 per cell, with grey representing no detectable expression and dark red indicating high expression. Data were obtained from the Sciatic Nerve ATlas (SNAT). Cell populations include: proliferating Schwann cells (prol. SC), immature Schwann cells (iSC), pro-myelinating Schwann cells (pmSCs), transition SCs (tSC), mature non-myelinating SCs (nm(R)SC) and myelinating SCs (mSC). (C) Dot plot comparing log 2 -normalized ZNF423 gene expression between PNF ( n =32), and MPNST ( n =14). P-values represent two-tailed unpaired t-test with Welch’s correction. (D) Dot plot comparing ZNF423 mRNA levels in normal nerve ( n =3), PNF ( n =26), and MPNST ( n =6) (GEO accession: GSE41747). Error bars reflect standard error of the mean (SEM). P-values represent two-tailed unpaired t-test with Welch’s correction. (E) Dot plot depicting log 2 -normalized counts of Zfp423 for each sample ( n =3 per group). Error bars reflect standard error of the mean (SEM). P-values represent unpaired, two-tailed t-test with Welch’s correction. (F) Dot plot depicting log 2 -normalized counts of Zfp423 following CRISPR-mediated knockout of <t>Suz12</t> compared to control ( n =3 per group). Error bars reflect standard error of the mean (SEM). P-values represent two-tailed unpaired t-test with Welch’s correction. ****=p-value≤0.0001, ***=p-value≤0.001, *=p-value≤0.05, ns=not significant.
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ZNF423/Zfp423 is aberrantly upregulated in both human and genetically engineered mouse models (GEMM) of MPNST compared to PNF and normal nerves. (A) Bar plot showing Zfp423 transcript expression (RPKM) across embryonic (E13.5, E17.5) and postnatal (P1, P5, P14, P24, and P60) murine developmental timepoints. (B) Merged tSNE plot generated from scRNAseq data of murine Schwann cells at P1, P5, P14, and P60 showing Zfp423 expression restricted to the immature Schwann cells (iSC) postnatally. The color gradient of grey to red indicates relative transcript abundance of Zfp423 per cell, with grey representing no detectable expression and dark red indicating high expression. Data were obtained from the Sciatic Nerve ATlas (SNAT). Cell populations include: proliferating Schwann cells (prol. SC), immature Schwann cells (iSC), pro-myelinating Schwann cells (pmSCs), transition SCs (tSC), mature non-myelinating SCs (nm(R)SC) and myelinating SCs (mSC). (C) Dot plot comparing log 2 -normalized ZNF423 gene expression between PNF ( n =32), and MPNST ( n =14). P-values represent two-tailed unpaired t-test with Welch’s correction. (D) Dot plot comparing ZNF423 mRNA levels in normal nerve ( n =3), PNF ( n =26), and MPNST ( n =6) (GEO accession: GSE41747). Error bars reflect standard error of the mean (SEM). P-values represent two-tailed unpaired t-test with Welch’s correction. (E) Dot plot depicting log 2 -normalized counts of Zfp423 for each sample ( n =3 per group). Error bars reflect standard error of the mean (SEM). P-values represent unpaired, two-tailed t-test with Welch’s correction. (F) Dot plot depicting log 2 -normalized counts of Zfp423 following CRISPR-mediated knockout of <t>Suz12</t> compared to control ( n =3 per group). Error bars reflect standard error of the mean (SEM). P-values represent two-tailed unpaired t-test with Welch’s correction. ****=p-value≤0.0001, ***=p-value≤0.001, *=p-value≤0.05, ns=not significant.
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ZNF423/Zfp423 is aberrantly upregulated in both human and genetically engineered mouse models (GEMM) of MPNST compared to PNF and normal nerves. (A) Bar plot showing Zfp423 transcript expression (RPKM) across embryonic (E13.5, E17.5) and postnatal (P1, P5, P14, P24, and P60) murine developmental timepoints. (B) Merged tSNE plot generated from scRNAseq data of murine Schwann cells at P1, P5, P14, and P60 showing Zfp423 expression restricted to the immature Schwann cells (iSC) postnatally. The color gradient of grey to red indicates relative transcript abundance of Zfp423 per cell, with grey representing no detectable expression and dark red indicating high expression. Data were obtained from the Sciatic Nerve ATlas (SNAT). Cell populations include: proliferating Schwann cells (prol. SC), immature Schwann cells (iSC), pro-myelinating Schwann cells (pmSCs), transition SCs (tSC), mature non-myelinating SCs (nm(R)SC) and myelinating SCs (mSC). (C) Dot plot comparing log 2 -normalized ZNF423 gene expression between PNF ( n =32), and MPNST ( n =14). P-values represent two-tailed unpaired t-test with Welch’s correction. (D) Dot plot comparing ZNF423 mRNA levels in normal nerve ( n =3), PNF ( n =26), and MPNST ( n =6) (GEO accession: GSE41747). Error bars reflect standard error of the mean (SEM). P-values represent two-tailed unpaired t-test with Welch’s correction. (E) Dot plot depicting log 2 -normalized counts of Zfp423 for each sample ( n =3 per group). Error bars reflect standard error of the mean (SEM). P-values represent unpaired, two-tailed t-test with Welch’s correction. (F) Dot plot depicting log 2 -normalized counts of Zfp423 following CRISPR-mediated knockout of <t>Suz12</t> compared to control ( n =3 per group). Error bars reflect standard error of the mean (SEM). P-values represent two-tailed unpaired t-test with Welch’s correction. ****=p-value≤0.0001, ***=p-value≤0.001, *=p-value≤0.05, ns=not significant.
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ZNF423/Zfp423 is aberrantly upregulated in both human and genetically engineered mouse models (GEMM) of MPNST compared to PNF and normal nerves. (A) Bar plot showing Zfp423 transcript expression (RPKM) across embryonic (E13.5, E17.5) and postnatal (P1, P5, P14, P24, and P60) murine developmental timepoints. (B) Merged tSNE plot generated from scRNAseq data of murine Schwann cells at P1, P5, P14, and P60 showing Zfp423 expression restricted to the immature Schwann cells (iSC) postnatally. The color gradient of grey to red indicates relative transcript abundance of Zfp423 per cell, with grey representing no detectable expression and dark red indicating high expression. Data were obtained from the Sciatic Nerve ATlas (SNAT). Cell populations include: proliferating Schwann cells (prol. SC), immature Schwann cells (iSC), pro-myelinating Schwann cells (pmSCs), transition SCs (tSC), mature non-myelinating SCs (nm(R)SC) and myelinating SCs (mSC). (C) Dot plot comparing log 2 -normalized ZNF423 gene expression between PNF ( n =32), and MPNST ( n =14). P-values represent two-tailed unpaired t-test with Welch’s correction. (D) Dot plot comparing ZNF423 mRNA levels in normal nerve ( n =3), PNF ( n =26), and MPNST ( n =6) (GEO accession: GSE41747). Error bars reflect standard error of the mean (SEM). P-values represent two-tailed unpaired t-test with Welch’s correction. (E) Dot plot depicting log 2 -normalized counts of Zfp423 for each sample ( n =3 per group). Error bars reflect standard error of the mean (SEM). P-values represent unpaired, two-tailed t-test with Welch’s correction. (F) Dot plot depicting log 2 -normalized counts of Zfp423 following CRISPR-mediated knockout of <t>Suz12</t> compared to control ( n =3 per group). Error bars reflect standard error of the mean (SEM). P-values represent two-tailed unpaired t-test with Welch’s correction. ****=p-value≤0.0001, ***=p-value≤0.001, *=p-value≤0.05, ns=not significant.
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ZNF423/Zfp423 is aberrantly upregulated in both human and genetically engineered mouse models (GEMM) of MPNST compared to PNF and normal nerves. (A) Bar plot showing Zfp423 transcript expression (RPKM) across embryonic (E13.5, E17.5) and postnatal (P1, P5, P14, P24, and P60) murine developmental timepoints. (B) Merged tSNE plot generated from scRNAseq data of murine Schwann cells at P1, P5, P14, and P60 showing Zfp423 expression restricted to the immature Schwann cells (iSC) postnatally. The color gradient of grey to red indicates relative transcript abundance of Zfp423 per cell, with grey representing no detectable expression and dark red indicating high expression. Data were obtained from the Sciatic Nerve ATlas (SNAT). Cell populations include: proliferating Schwann cells (prol. SC), immature Schwann cells (iSC), pro-myelinating Schwann cells (pmSCs), transition SCs (tSC), mature non-myelinating SCs (nm(R)SC) and myelinating SCs (mSC). (C) Dot plot comparing log 2 -normalized ZNF423 gene expression between PNF ( n =32), and MPNST ( n =14). P-values represent two-tailed unpaired t-test with Welch’s correction. (D) Dot plot comparing ZNF423 mRNA levels in normal nerve ( n =3), PNF ( n =26), and MPNST ( n =6) (GEO accession: GSE41747). Error bars reflect standard error of the mean (SEM). P-values represent two-tailed unpaired t-test with Welch’s correction. (E) Dot plot depicting log 2 -normalized counts of Zfp423 for each sample ( n =3 per group). Error bars reflect standard error of the mean (SEM). P-values represent unpaired, two-tailed t-test with Welch’s correction. (F) Dot plot depicting log 2 -normalized counts of Zfp423 following CRISPR-mediated knockout of <t>Suz12</t> compared to control ( n =3 per group). Error bars reflect standard error of the mean (SEM). P-values represent two-tailed unpaired t-test with Welch’s correction. ****=p-value≤0.0001, ***=p-value≤0.001, *=p-value≤0.05, ns=not significant.
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ZNF423/Zfp423 is aberrantly upregulated in both human and genetically engineered mouse models (GEMM) of MPNST compared to PNF and normal nerves. (A) Bar plot showing Zfp423 transcript expression (RPKM) across embryonic (E13.5, E17.5) and postnatal (P1, P5, P14, P24, and P60) murine developmental timepoints. (B) Merged tSNE plot generated from scRNAseq data of murine Schwann cells at P1, P5, P14, and P60 showing Zfp423 expression restricted to the immature Schwann cells (iSC) postnatally. The color gradient of grey to red indicates relative transcript abundance of Zfp423 per cell, with grey representing no detectable expression and dark red indicating high expression. Data were obtained from the Sciatic Nerve ATlas (SNAT). Cell populations include: proliferating Schwann cells (prol. SC), immature Schwann cells (iSC), pro-myelinating Schwann cells (pmSCs), transition SCs (tSC), mature non-myelinating SCs (nm(R)SC) and myelinating SCs (mSC). (C) Dot plot comparing log 2 -normalized ZNF423 gene expression between PNF ( n =32), and MPNST ( n =14). P-values represent two-tailed unpaired t-test with Welch’s correction. (D) Dot plot comparing ZNF423 mRNA levels in normal nerve ( n =3), PNF ( n =26), and MPNST ( n =6) (GEO accession: GSE41747). Error bars reflect standard error of the mean (SEM). P-values represent two-tailed unpaired t-test with Welch’s correction. (E) Dot plot depicting log 2 -normalized counts of Zfp423 for each sample ( n =3 per group). Error bars reflect standard error of the mean (SEM). P-values represent unpaired, two-tailed t-test with Welch’s correction. (F) Dot plot depicting log 2 -normalized counts of Zfp423 following CRISPR-mediated knockout of Suz12 compared to control ( n =3 per group). Error bars reflect standard error of the mean (SEM). P-values represent two-tailed unpaired t-test with Welch’s correction. ****=p-value≤0.0001, ***=p-value≤0.001, *=p-value≤0.05, ns=not significant.

Journal: bioRxiv

Article Title: ZNF423 depletion induces the integrated stress response and represents a potential vulnerability in NF1-associated MPNST

doi: 10.64898/2026.03.03.709360

Figure Lengend Snippet: ZNF423/Zfp423 is aberrantly upregulated in both human and genetically engineered mouse models (GEMM) of MPNST compared to PNF and normal nerves. (A) Bar plot showing Zfp423 transcript expression (RPKM) across embryonic (E13.5, E17.5) and postnatal (P1, P5, P14, P24, and P60) murine developmental timepoints. (B) Merged tSNE plot generated from scRNAseq data of murine Schwann cells at P1, P5, P14, and P60 showing Zfp423 expression restricted to the immature Schwann cells (iSC) postnatally. The color gradient of grey to red indicates relative transcript abundance of Zfp423 per cell, with grey representing no detectable expression and dark red indicating high expression. Data were obtained from the Sciatic Nerve ATlas (SNAT). Cell populations include: proliferating Schwann cells (prol. SC), immature Schwann cells (iSC), pro-myelinating Schwann cells (pmSCs), transition SCs (tSC), mature non-myelinating SCs (nm(R)SC) and myelinating SCs (mSC). (C) Dot plot comparing log 2 -normalized ZNF423 gene expression between PNF ( n =32), and MPNST ( n =14). P-values represent two-tailed unpaired t-test with Welch’s correction. (D) Dot plot comparing ZNF423 mRNA levels in normal nerve ( n =3), PNF ( n =26), and MPNST ( n =6) (GEO accession: GSE41747). Error bars reflect standard error of the mean (SEM). P-values represent two-tailed unpaired t-test with Welch’s correction. (E) Dot plot depicting log 2 -normalized counts of Zfp423 for each sample ( n =3 per group). Error bars reflect standard error of the mean (SEM). P-values represent unpaired, two-tailed t-test with Welch’s correction. (F) Dot plot depicting log 2 -normalized counts of Zfp423 following CRISPR-mediated knockout of Suz12 compared to control ( n =3 per group). Error bars reflect standard error of the mean (SEM). P-values represent two-tailed unpaired t-test with Welch’s correction. ****=p-value≤0.0001, ***=p-value≤0.001, *=p-value≤0.05, ns=not significant.

Article Snippet: Immunoblots were performed using primary antibodies against ZNF423 (ABN410, Sigma-Aldrich), GAPDH (sc-365062, Santa Cruz Biotechnology), SUZ12 (3737S, Cell Signaling Technology), ATF3 (18665S, Cell Signaling Technology), ATF4 (11815S, Cell Signaling Technology), PARP (9542S, Cell Signaling Technology), and γH2A.x (9718S, Cell Signaling Technology).

Techniques: Expressing, Generated, Gene Expression, Two Tailed Test, CRISPR, Knock-Out, Control