A Nuclear factor I-X mediated regulatory network governs the balance of hematopoietic stem and progenitor cells during hematopoiesis
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ABSTRACT:
PROVIDER: PRJNA702429 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13730529.fastq.gz | Fastqsanger.gz | |||
| SRR13730530.fastq.gz | Fastqsanger.gz | |||
| SRR13730531.fastq.gz | Fastqsanger.gz | |||
| SRR13730532.fastq.gz | Fastqsanger.gz | |||
| SRR13730533.fastq.gz | Fastqsanger.gz |
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Project description:The transcription factor (TF), nuclear factor I-X (NFIX), is a positive regulator of hematopoietic stem and progenitor cell (HSPC) transplantation. Nfix-deficient HSPC exhibit a severe loss of repopulating activity, increased apoptosis and a loss of colony forming potential. However, the underlying mechanism remains elusive. Here, we performed cellular indexing of transcriptomes and epitopes by high-throughput sequencing (CITE-seq) on Nfix-deficient HSPC and observed loss of long-term hematopoietic stem cells (LT-HSC) and an accumulation of megakaryocyte and myelo-erythroid progenitors. The genome-wide binding profile of NFIX in primitive murine hematopoietic cells revealed its co-localization with other hematopoietic TFs such as PU.1. We confirmed the physical interaction between NFIX and PU.1 and unveiled that the two TFs co-occupy super-enhancers and regulate genes implicated in cellular respiration and hematopoietic differentiation. Our data support a model in which NFIX collaborates with PU.1 at super-enhancers to promote the differentiation of hematopoietic progenitors.
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Project description:Long non-coding RNAs (lncRNAs) exert regulatory functions in a wide spectrum of biological contexts, and certain regulatory functions involve the formation of RNA-protein complexes. Discovering the structure/function of these complexes may unveil important functional insights. The DDX41 gene encoding the DEAD-box RNA helicase 41 protein (DDX41) is subject to extensive germline genetic variation, and certain variants create a predisposition to develop myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). While the importance of DDX41 for the control of hematopoiesis is established, many questions remain regarding the mechanisms of how DDX41 functions in hematopoietic stem and progenitor cells. Previously, we identified a DDX41-regulated lncRNA, growth arrest-specific 5 (Gas5) (Kim et al.). As Gas5 function in hematopoiesis is unknown, we analyzed protein interactors of Gas5 lncRNA using HyPR-MS (Hybridization Purification of RNA-Protein complexes followed by Mass Spectrometry). 28 proteins were identified as Gas5 lncRNA interactors, five of which were experimentally validated as Gas5 lncRNA interactors by RNA Immunoprecipitation qPCR (RIP-qPCR) analysis. The identification of protein interactors with a DDX41-regulated lncRNA establishes a foundation to guide future mechanistic and biological studies.c
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Project description:Long non-coding RNAs (lncRNAs) exert regulatory functions in a wide spectrum of biological contexts, and certain regulatory functions involve the formation of RNA-protein complexes. Discovering the structure/function of these complexes may unveil important functional insights. The DDX41 gene encoding the DEAD-box RNA helicase 41 protein (DDX41) is subject to extensive germline genetic variation, and certain variants create a predisposition to develop myelodysplastic syndrome and acute myeloid leukemia. While the importance of DDX41 for the control of hematopoiesis is established, many questions remain regarding the mechanisms of how DDX41 functions in hematopoietic stem and progenitor cells. Previously, we identified a DDX41-regulated lncRNA, growth arrest-specific 5 (Gas5). As Gas5 function in hematopoiesis is unknown, we analyzed protein interactors of Gas5 lncRNA using HyPR-MS (Hybridization Purification of RNA-Protein complexes followed by Mass Spectrometry). 303 proteins were identified as Gas5 lncRNA interactors, five of which were experimentally validated as Gas5 lncRNA interactors by RNA Immunoprecipitation qPCR (RIP-qPCR) analysis. The identification of protein interactors with a DDX41-regulated lncRNA establishes a foundation to guide future mechanistic and biological studies.
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