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HMGA1 Chromatin Regulators Drive MPN Progression [RNA-Seq]

GSE183374 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2023/10/05 Platform GPL11154
At a glance

RNA-seq (gene expression) · human · 12 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Topic
Myeloproliferative neoplasmsThis series is part of our curated briefing on it.
Samples
12 samples
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Summary (written by the submitters)
Myeloproliferative neoplasms (MPN) transform to myelofibrosis (MF) and highly lethal acute myeloid leukemia (AML), although actionable mechanisms driving progression remain elusive. The HMGA1 chromatin regulator is up-regulated during MPN progression with highest levels after transformation. HMGA1 depletion in JAK2V617F MPN AML cell lines disrupts proliferation, clonogenicity, and leukemic engraftment.
Read the full summary ↓
Surprisingly, loss of just a single Hmga1 allele prevents progression to MF in JAK2V617F transgenic mice, decreasing blood counts and expansion in stem and myeloid progenitors while preventing splenomegaly and fibrosis within the spleen and bone marrow. RNA sequencing revealed HMGA1-dependent transcriptional networks that govern proliferation (E2F, G2M, mitosis, MYC targets) and cell fate, including the GATA2 master regulatory gene. Silencing GATA2 recapitulates phenotypes observed with HMGA1 depletion whereas GATA2 re-expression partially rescues leukemogenesis. HMGA1 transactivates GATA2 through sequences near the developmental enhancer (+9.5), increasing chromatin accessibility and recruiting active histone marks. Further, HMGA1 transcriptional networks, including GATA2, are activated in human MF after leukemic transformation. Further, HMGA1 depletion synergizes with the JAK2 inhibitor, ruxolitinib, to prolong survival in murine MPN AML. These findings illuminate HMGA1 as a key epigenetic switch required for MPN transformation and promising therapeutic target to treat or prevent disease progression.
This dataset
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE183374_RAW.tar (it can run to tens of gigabytes).

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA760443 and SRA study SRP335549. Searching any of these in the dataset finder brings you back here.

Samples in this study

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+ 12 more — browse all 12 samples with per-sample file links →

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