Page 40 - M. Immunology

[M. Immunology-26]

Phc2 regulates the migration of hematopoietic stem and

progenitor cell by suppressing Vcam1 expression from bone

marrow niche

June Yang¹, Taehoon Chun¹˙*

¹College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea

To provide hematopoietic and tissue-resident leukocyte homeostasis, efficient recruitment of hematopoietic stem
and progenitor cells (HSPCs) is of utmost importance. Mechanisms on migration of HSPCs between bone marrow
and peripheral tissue is not well understood and is of great interest in the clinical field because controlling the

mobility of immune cells impacts the clinical results. Here we show an epigenetic factor, Phc2, as a modulator of
HSPC migration. Phc2 gene deficiency in mice leads to malfunction of HSPC trafficking through suppressed Vcam1

gene expression in bone marrow stromal cells (BMSCs), ultimately culminate with a overall immunodeficiency.
Moreover, the pharmacological inhibition of VCAM-1 in Phc2 knockout mice reverses the symptoms. We also showed

that inhibition of Vcam1 gene in a Phc2-dependent manner in BMSCs is controlled by other epigenetic factors
H2AK119ub and H3K27me3. In total, our results suggest a critical role for Phc2 in controlling the migration of

HSPCs by regulating bone marrow microenvironment.