Neuropathy of the haematopoietic stem cell niche is essential for myeloproliferative neoplasms [RNA-seq]

ABSTRACT: Myeloproliferative neoplasms (MPNs) are diseases caused by mutations in the haematopoietic stem cell (HSC) compartment. Most MPN patients have a common acquired mutation of Janus kinase 2 (JAK2) gene in HSCs that renders this kinase constitutively active, leading to uncontrolled cell expansion. The bone marrow (BM) microenvironment might contribute to the clinical outcomes of this common event. We previously showed that BM nestin+ mesenchymal stem cells (MSCs) innervated by sympathetic nerve fibres regulate normal HSCs. Here we demonstrate that abrogation of this regulatory circuit is essential for MPN pathogenesis. Sympathetic nerve fibres, supporting Schwann cells and nestin+ MSCs are consistently reduced in the BM of MPN patients and mice expressing the human JAK2V617F mutation in HSCs.

ORGANISM(S): Mus musculus

SUBMITTER: Simón Méndez-Ferrer 

PROVIDER: E-GEOD-55798 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress