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| Status |
Public on Dec 02, 2022 |
| Title |
A Nuclear factor I-X mediated regulatory network governs the balance of hematopoietic stem and progenitor cells during hematopoiesis |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Other
|
| Summary |
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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| |
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| Overall design |
scRNA-seq of NFIX WT and KO bone marrow cells, NFIX,PU.1 CHIP-seq, ATAC-seq, and H3K27ac ChIP-seq in HPC5 cells.
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| |
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| Contributor(s) |
Walker M, Li Y, Cheng Y, McKinney-Freeman S |
| Citation(s) |
36478187 |
| |
| Submission date |
Feb 17, 2021 |
| Last update date |
Mar 03, 2023 |
| Contact name |
Shannon McKinney-Freeman |
| E-mail(s) |
Shannon.McKinney-Freeman@STJUDE.ORG
|
| Organization name |
St. Jude Children’s Research Hospital
|
| Department |
Department of Hematology
|
| Street address |
262 Danny Thomas Place
|
| City |
Memphis |
| State/province |
TN |
| ZIP/Postal code |
38018 |
| Country |
USA |
| |
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| Platforms (2) |
| GPL21626 |
NextSeq 550 (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (24)
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| Relations |
| BioProject |
PRJNA702429 |
| SRA |
SRP306824 |
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