HMGA1 chromatin regulators drive transcriptional networks involved in megakaryocyte expansion, fibrosis, and sensitivity to interferon signaling in JAK2-V617F MPN
Experiments reveal HMGA1's role in thrombocytosis and inflammation in myeloproliferative neoplasms, indicating potential for targeted interferon therapy.
Key Points
This research aims to define the mechanisms by which HMGA1 influences myeloproliferative neoplasms and sensitivity to interferon.
Compared transcriptomes via single cell RNA sequencing in HSCs and progenitor cells from mice.
Assessed responses to IFNα in various HSPC phenotypes and patient blood samples.
Utilized gene set enrichment analysis to define cellular pathways.
Hmga1 haploinsufficiency reduces expansion of hematopoietic stem cells and megakaryocyte-biased HSCs.
IFNα therapy normalizes blood counts in JAK2V617F mice with intact Hmga1.
HSPC with intact Hmga1 show increased differentiation and sensitivity to IFNα.