Deficiency of Antioxidative Paraoxonase 2 (Pon2) Leads to Increased Number of Phenotypic LT-HSCs and Disturbed Erythropoiesis.

ABSTRACT:

Background

Long-term hematopoietic stem cells (LT-HSCs) reside in bone marrow niches with tightly controlled reactive oxygen species (ROS) levels. ROS increase results into LT-HSC differentiation and stem cell exhaustion. Paraoxonase 2 (PON2) has been shown to be important for ROS control.

Objectives

We investigate the effects of inactivation of the PON2 gene on hematopoietic cell differentiation and activity.

Methods and results

In young mice with inactivated Pon2 gene (Pon2 ^-/-, <3 months), we observed an increase of LT-HSCs and a reduced frequency of progenitor cells. In competitive transplantations, young Pon2^-/- BM outcompeted WT BM at early time points. ROS levels were significantly increased in Pon2^-/-</

SUBMITTER: Spiecker L 

PROVIDER: S-EPMC8253644 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature