1021 – SYNDECAN-2 EXPRESSION MARKS HEMATOPOIETIC STEM CELLS AND REGULATES STEM CELL REPOPULATING CAPACITY

• Published in: Experimental hematology Vol. 100; p. S24
• Main Authors: Termini, Christina, Pang, Amara, Li, Michelle, Fang, Tiancheng, Chang, Vivian, Chute, John
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.08.2021
• ISSN: 0301-472X; 1873-2399
• DOI: 10.1016/j.exphem.2021.12.015

The discovery of hematopoietic stem cell (HSC) surface markers can enhance understanding of HSC identity and function. We discovered a population of murine bone marrow (BM) HSCs distinguished by their expression of the heparan sulfate proteoglycan, Syndecan-2, which serves as both a marker and regulator of HSC function. We first quantified Syndecan-2 expression on murine BM HSCs and multipotent progenitors (MPP), determining that Syndecan-2 is enriched ten-fold on the surface of HSCs compared to MPPs. Using competitive repopulation assays, we determined that Syndecan-2+ CD34−c-Kit+Sca-1+Lineage− HSCs exhibited significantly increased hematopoietic repopulating capacity compared to Syndecan-2− HSCs, suggesting that Syndecan-2 marks HSCs with enhanced functional ability. We next analyzed the role of Syndecan-2 in HSC function using a lentiviral shRNA knockdown approach, demonstrating that Syndecan-2 knockdown significantly reduced HSC self-renewal compared to control HSCs. Given the role of Syndecan-2 in cellular proliferation, we tested whether Syndecan-2 might affect HSC function through regulation of HSC cycling. We detected significantly decreased G0 HSCs upon Syndecan-2 knockdown compared to control HSCs, concomitant with decreased Cdkn1c expression. We next used a double knockdown system to reduce the expression of both Sdc2 and Cdkn1c. We determined that knockdown of both Sdc2 and Cdkn1c did not further reduce the proportion of G0 quiescent HSCs compared to Sdc2 knockdown alone, suggesting that Syndecan-2 regulates HSC cycling through Cdkn1c. Quantification of hematopoietic colony formation demonstrated that knockdown of Sdc2, Cdkn1c or both similarly diminished colony formation compared to control conditions, underscoring the importance of Syndecan-2 in regulating hematopoietic differentiation. Taken together, our studies reveal that Syndecan-2 is a novel marker of HSCs which regulates HSC function through cell cycle regulation by Cdkn1c.