Accession |
PRJCA000384 |
Title |
Human NOTCH4 Is a Key Target of RUNX1 in Megakaryocytic Differentiation |
Relevance |
Medical |
Data types |
Epigenomics
|
Organisms |
Homo sapiens
|
Description |
Megakaryocytes (MKs) in adult marrow produce platelets that play important roles in blood coagulation and hemostasis. Mono-allelic mutations of the master transcription factor RUNX1 lead to familial platelet disorder (FPD) characterized by defective MK and platelet development. However, the molecular mechanisms in FPD remain unclear. Previously, we generated human induced pluripotent stem cells (iPSCs) from FPD patients containing a RUNX1 nonsense mutation: Indeed MKs developed from FPD-iPSCs was reduced and targeted correction of the RUNX1 mutation restored MK production. In this study, we took advantage of isogenic pairs of FPD-iPSCs and MK differentiation system to identify RUNX1 direct target genes. Using integrative genomic and bioinformatic analysis of hematopoietic progenitor cells generated from FPD iPSCs and mutation-corrected isogenic control, we identified two gene sets whose transcription are either up- or down-regulated by RUNX1 binding in mutation-corrected and normal iPSCs. |
Sample scope |
Monoisolate |
Release date |
2018-01-01 |
Publication |
|
Submitter |
Chen
Jin (jinchen@big.ac.cn)
|
Organization |
Beijing Institute of Genomics, Chinese Academy of Sciences |
Submission date |
2017-03-21 |