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Differential DNA methylation occurs in RUNX1 heterozygous mutations harboring hematopoietic progenitor cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below

ORGANISM(S): Homo sapiens

PROVIDER: GSE245771 | GEO | 2024/02/26

REPOSITORIES: GEO

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Differential DNA methylation occurs in RUNX1 heterozygous mutations harboring hematopoietic progenitor cells [EM]

Project description:Background: Familial platelet disorder (FPD) is an autosomal dominant disease caused by a heterozygous germline mutation inRUNX1. FPD patients show not only thrombocytopenia with platelet dysfunction, but also a high level of developing hematological malignancies, strongly suggesting that FPD is in a precancerous state. However, the DNA methylation status of FPD has not yet been elucidated due to no animal models for FPD and the difficulty in obtaining FPD patient-derived samples. Results: We found that differentiation efficiencies into HPCs and megakaryocytes was reduced in the FPD-mimicking cells, which were established by genome editing for human iPS cells as a FPD-model, compared with those of wild-type cells. The FPD-mimicking HPCs were subjected to DNA methylation analysis, and the HPCs showed the distinct DNA methylation patterns compared to wild-type HPCs. Furthermore, we demonstrated a putative causative transcription factor of the differential DNA hypermethylation, which are involved in both promoting the binding site-directed DNA demethylation and regulating megakaryopoiesis.

2024-02-26 | GSE245765 | GEO

Differential DNA methylation occurs in RUNX1 heterozygous mutations harboring hematopoietic progenitor cells [FLI1_EM]

2024-02-26 | GSE245769 | GEO

Differential DNA methylation occurs in RUNX1 heterozygous mutations harboring hematopoietic progenitor cells [WES]

2024-02-26 | GSE245770 | GEO

Differential DNA methylation occurs in RUNX1 heterozygous mutations harboring hematopoietic progenitor cells [YX-FLI1_EM]

2024-02-26 | GSE249049 | GEO

Aberrant DNA methylation occurs in RUNX1 heterozygous mutations harboring hematopoietic progenitor cells [CUT&RUN]

Project description:Background: Familial platelet disorder with associated myeloid malignancies (FPDMM) is an autosomal dominant disease caused by a heterozygous germline mutation inRUNX1. The patients with FPDMM show not only thrombocytopenia with platelet dysfunction, but also a high level of developing hematological malignancies, strongly suggesting that FPDMM is in a precancerous state. However, the DNA methylation status of FPDMM has not yet been elucidated due to no animal models for FPDMM and the difficulty in obtaining the patient-derived samples. Results: We found that differentiation efficiencies into HPCs and megakaryocytes was reduced in the FPDMM-mimicking cells, which were established by genome editing for human iPS cells as a FPDMM-model, compared with those of wild-type cells. The FPDMM-mimicking HPCs were subjected to DNA methylation analysis, and the HPCs showed the distinct DNA methylation patterns compared to wild-type HPCs. Furthermore, we identified FLI1 as a putative causative transcription factor of the differential DNA hypermethylation involved in both promoting the binding site-directed DNA demethylation and regulating megakaryopoiesis.

2024-07-01 | GSE270829 | GEO

Differential DNA methylation occurs in RUNX1 heterozygous mutations harboring hematopoietic progenitor cells

Project description:Differential DNA methylation occurs in RUNX1 heterozygous mutations harboring hematopoietic progenitor cells

| PRJNA1029939 | ENA

Differential DNA methylation occurs in RUNX1 heterozygous mutations harboring hematopoietic progenitor cells [EM]

Project description:Differential DNA methylation occurs in RUNX1 heterozygous mutations harboring hematopoietic progenitor cells [EM]

| PRJNA1029948 | ENA

Differential DNA methylation occurs in RUNX1 heterozygous mutations harboring hematopoietic progenitor cells [FLI1_EM]

Project description:Differential DNA methylation occurs in RUNX1 heterozygous mutations harboring hematopoietic progenitor cells [FLI1_EM]

| PRJNA1029949 | ENA

Differential DNA methylation occurs in RUNX1 heterozygous mutations harboring hematopoietic progenitor cells [WES]

Project description:Differential DNA methylation occurs in RUNX1 heterozygous mutations harboring hematopoietic progenitor cells [WES]