Journal: Nature Genetics

Article Title: Transposable elements shape stemness in normal and leukemic hematopoiesis

doi: 10.1038/s41588-026-02585-z

Figure Lengend Snippet: a – c ) Heatmap showing differential accessibility Z-scores for LSC TEs (q < 0.01 LSC+ vs LSC-) between ATAC-seq profiles of LSC + , LSC- fractions and bulk AML tumors (cohort1 in a , cohort2 in b and cohort3 in c ), clustered based on correlation. Note that 20, 40 and 41 samples cluster with LSC+ fractions in cohort1, cohort2 and cohort3 bulk AML patients, respectively. d ) Boxplot of LSCTE121 Z-score in LSC fractions (LSC+, n = 11; LSC-, n = 24). Boxplots show the median and upper and lower quartiles; whiskers represent 1.5× interquartile range (IQR). P-value results of Benjamini-Hochberg corrected two-sided Wilcoxon test are showcased. e ) Pearson correlation between LSCTE121 Z-score and blast count in peripheral blood for cohort1 bulk AML patients. The linear regression line is shown in blue and the confidence interval is shown in gray. P-value results of null-hypothesis testing are showcased on the plots. f ) Same as panel e but for cohort2 bulk AML patients. The linear regression line is shown in blue and the confidence interval is shown in gray. P-value results of null-hypothesis testing are showcased on the plots. g ) Same as panel e but for cohort3 bulk AML patients. The linear regression line is shown in blue and the confidence interval is shown in gray. P-value results of null-hypothesis testing are showcased on the plots. h ) Kaplan–Meier estimates using overall survival as a clinical endpoint for LSCTE121 Z-score top vs bottom 25 percentile in cohort1 (n = 8/group). log rank (Mantel–Cox) p-values are shown on the Kaplan–Meier curves. i ) Kaplan-Meier estimates using overall survival as a clinical endpoint, patient division based on LSC17-high vs low scores in cohort1 bulk AML patients; LSC17-high: n = 12, LSC17-low: n = 17. log rank (Mantel–Cox) p-values are shown on the Kaplan–Meier curves. j ) Violin plots for the ATAC-seq signal over TE elements around (+/-2kb) LSC17 genes in LSC+ and LSC- fractions. P-value results of the Wilcoxon test are showcased. k ) Violin plots for the ATAC-seq signal over TE elements around (+/-2kb) LSC17 genes compared to all other genes in the human genome. P-value results of the Wilcoxon test are showcased. l ) Violin plots for the ATAC-seq signal over TE elements around (+/-2kb) LSC17 genes and around 100 independent groups of 17 size-matched, randomly selected genes. p-value results of Benjamini-Hochberg corrected pairwise Wilcoxon test are showcased. m ) UpSet plot showing the intersection of REACTOME pathways with increased chromatin accessibility in LSC17-high or LSCTE121-high patients (cohort1). n ) Volcano plot showing the log2 fold-change chromatin accessibility for each cell cycle gene promoter (TSS) between LSCTE121-high and LSCTE121-low patients (cohort1) versus the −log10, resulted from Wald test, p-value for that fold-change. o ) Volcano plot showing the log2 fold-change chromatin accessibility for each IL10 signaling gene promoter (TSS) between LSC17-high and LSC17-low patients (cohort1) versus the −log10 p-value for that fold-change. p ) Same as panel h but for cohort2 patients (LSCTE121-high: n = 15; LSCTE121-low: n = 45). q ) Same as panel h but for cohort3 patients (LSCTE121-high: n = 35; LSCTE121-low: n = 42).

Article Snippet: We next computed a single LSCTE121 z score by combining enrichment of LSC+ TE subfamilies and depletion of LSC− TE subfamilies using Stouffer’s method ( ).

Techniques:

Journal: Nature Genetics

Article Title: Transposable elements shape stemness in normal and leukemic hematopoiesis

doi: 10.1038/s41588-026-02585-z

Figure Lengend Snippet: a , Heatmap showing differential accessibility z scores for LSCTE121 ( q < 0.01 LSC+ versus LSC−) in bulk cohort1 AML tumors. Please note that bulk tumors do not cluster according to their LSC17 scores with LSC+ or LSC− fractions. b , Boxplot displaying the LSCTE121 z score in cohort1 patients ( n = 29). Patients were divided into LSCTE121-high or low based on the heatmaps in a . Boxplots show the median and upper and lower quartiles; whiskers represent 1.5× IQR. P- value results of the two-sided Wilcoxon test are showcased on the boxplots. c , Kaplan–Meier estimates using disease-free interval as a clinical endpoint for LSCTE121 z score top versus bottom 25 percentile in cohort1 ( n = 8 per group). The log-rank (Mantel–Cox) P values are shown on the Kaplan–Meier curves. d , Pearson correlation between LSC17 score and LSCTE121 z score in cohort1 bulk AML patients. The linear regression line is shown in blue and the confidence interval is shown in gray. P -value results of null-hypothesis testing are showcased on the plots. e , GSEA enrichment plots showcasing significantly increased chromatin accessibility at cell cycle gene promoters (TSS) in LSC17-high patients (cohort1). P -value results of two-sided weighted Kolmogorov–Smirnov test are showcased on the plots. f , Volcano plot showing the log2 fold change chromatin accessibility for each cell cycle gene promoter (TSS) between LSC17-high and LSC17-low patients (cohort1) versus the −log 10 ( P ), resulting from the Wald test, for that fold change. g , GSEA enrichment plots showcasing significant increased chromatin accessibility at IL10 signaling gene promoters (TSS) in LSCTE121-high patients (cohort1). P values results of weighted Kolmogorov–Smirnov test are showcased on the plots. h , Volcano plot showing the log2 fold change chromatin accessibility for each IL10 signaling gene promoter (TSS) between LSCTE121-high and LSCTE121-low patients (cohort1) versus the −log 10 , resulting from the Wald test, P values for that fold change. i , Boxplot of LSCTE121 z score in LSC fractions ( n = 35; high, n = 1; med, n = 6; low, n = 4; NE, n = 24). Please note that engrafting fractions show a higher LSCTE121 z score than nonengrafting fractions. Boxplots show the median and upper and lower quartiles; whiskers represent 1.5× IQR. P values results of two-sided paired Wilcoxon test are showcased. j , Same as a , but for cohort2 patients (LSCTE121-high, n = 15; LSCTE121-low, n = 45). k , Same as b , but for cohort2 patients (LSCTE121-high, n = 15; LSCTE121-low, n = 45). Boxplots show the median and upper and lower quartiles; whiskers represent 1.5× IQR. P- value results of the two-sided Wilcoxon test are shown in the boxplots. l , Same as c , but for cohort2 patients (LSCTE121-high, n = 15; LSCTE121-low, n = 45). The log-rank (Mantel–Cox) P values are shown on the Kaplan–Meier curves. m , Same as a , but for cohort3 patients (LSCTE121-high, n = 35; LSCTE121-low, n = 42). n , Same as b , but for cohort3 patients (LSCTE121-high, n = 35; LSCTE121-low, n = 42). Boxplots show the median and upper and lower quartiles; whiskers represent 1.5× IQR. P- value results of the two-sided Wilcoxon test are showcased on the boxplots. o , Same as c , but for cohort3 patients (LSCTE121-high, n = 35; LSCTE121-low, n = 42). The log-rank (Mantel–Cox) P values are shown on the Kaplan–Meier curves. GSEA, gene set enrichment analysis.

Article Snippet: We next computed a single LSCTE121 z score by combining enrichment of LSC+ TE subfamilies and depletion of LSC− TE subfamilies using Stouffer’s method ( ).

Techniques:

Journal: Nature Genetics

Article Title: Transposable elements shape stemness in normal and leukemic hematopoiesis

doi: 10.1038/s41588-026-02585-z

Figure Lengend Snippet: a ) Boxplot displaying the LSCTE121 Z-score in LSCs (n = 35), OCI-AML22 fractions (n = 8), OCI-AML3 (n = 3) and MOLM13 (n = 3) cell lines. Boxplots show the median and upper and lower quartiles; whiskers represent 1.5× interquartile range (IQR). p-values results of the two-sided Wilcoxon test are showcased. b ) Violin plot for the difference of ATAC-seq signal between LSC+ and LSC- fractions over LTR12C elements (each dot corresponds to one LTR12C element). c ) Boxplot displaying the L1PA7 accessibility Z-scores in LSC+ (n = 11) and LSC− (n = 24). Boxplots show the median and upper and lower quartiles; whiskers represent 1.5× interquartile range (IQR). q-value corresponding to Benjamini-Hochberg corrected two-sided Wilcoxon signed rank test is showcased. d ) ATAC-seq signal profile across all L1PA7 elements accessible in LSC+ and/or LSC- fractions. e ) Violin plot for the ATAC-seq signal over L1PA7 elements accessible in LSC+ (n = 11) and/or LSC- (n = 24) fractions (left). Violin plot for the difference of ATAC-seq signal between LSC+ and LSC- fractions over L1PA7 elements (each dot corresponds to one L1PA7 element—right). Violin plots show the median value of the distributions. p-value results of paired samples Wilcoxon test are showcased. f ) Number of LTR12C (left) and L1PA7 (right) elements accessible in LSC+ (n = 11) and LSC- (n = 24) fractions. p-value results of two-sided Student’s t-test are showcased. g ) Boxplot displaying the LTR12C accessibility Z-scores in OCI-AML22 fractions (n = 8). Boxplots show the median and upper and lower quartiles; whiskers represent 1.5× interquartile range (IQR). h ) Boxplot displaying the L1PA7 accessibility Z-scores in OCI-AML22 fractions (n = 8). Boxplots show the median and upper and lower quartiles; whiskers represent 1.5× interquartile range (IQR). i ) Boxplot displaying the LTR12C accessibility Z-scores in OCI-AML3 (n = 3) and MOLM13 (n = 3) cell lines. Boxplots show the median and upper and lower quartiles; whiskers represent 1.5 × interquartile range (IQR). j ) Violin plots showcasing the chromatin accessibility signal distribution in OCI-AML3 stably expressing both CRISPRi and scramble (control in gray) or LTR12C (purple) guide RNA combos, over LTR12C or LTR12D. Every dot represents an individual TE element. Note that the loss of chromatin accessibility is specific to LTR12C elements only. p-values results of two-sided paired Wilcoxon test are showcased. k ) Violin plots showcasing the chromatin accessibility signal distribution in OCI-AML3 stably expressing both CRISPRi and scramble (control in gray) or LTR12C (purple) guide RNA combos over all LTR12 TE subfamilies, except LTR12C and LTR12D (in I ). Every dot represents an individual TE element. Violin plots show the median value of the distributions. p-values results of two-sided paired Wilcoxon test are showcased. l ) ATAC signal over LTR12C elements in CRISPRi OCI-AML3. Every dot corresponds to one LTR12C element; the x-axis represents the log2 of the normalized ATAC signal intensity in OCI-AML22-LSC+ stably expressing both CRISPRi and scramble guide RNA combo, while the y-axis represents the log2 normalized ATAC signal intensity in OCI-AML22-LSC+ stably expressing both CRISPRi and LTR12C guide RNA combo. m ) Same as panel k but for H3K27ac signal. LTR12C and LTR12D subfamilies are shown in Fig. . Violin plots show the median value of the distributions. P-values results of two-sided paired Wilcoxon test are showcased. n ) Same as panel l but for H3K27ac signal. o ) Same as panel k but for H3K9me3 signal. LTR12C and LTR12D subfamilies are shown in Fig. . Violin plots show the median value of the distributions. P-values results of two-sided paired Wilcoxon test are showcased. p ) Same as panel l but for H3K9me3 signal.

Article Snippet: We next computed a single LSCTE121 z score by combining enrichment of LSC+ TE subfamilies and depletion of LSC− TE subfamilies using Stouffer’s method ( ).

Techniques: Stable Transfection, Expressing, Control