Syndecan-2 Enriches for Hematopoietic Stem Cells and Regulates Stem Cell Repopulating Capacity

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2021 Nov 12

PMID 34767029

Citations 10

Authors

Christina M Termini

Amara Pang

Michelle Li

Tiancheng Fang

Vivian Y Chang

John P Chute

Affiliations

Soon will be listed here.

Abstract

The discovery of novel hematopoietic stem cell (HSC) surface markers can enhance understanding of HSC identity and function. We have discovered a population of primitive bone marrow (BM) HSCs distinguished by their expression of the heparan sulfate proteoglycan Syndecan-2, which serves as both a marker and a regulator of HSC function. Syndecan-2 expression was increased 10-fold in CD150+CD48-CD34-c-Kit+Sca-1+Lineage- cells (long-term HSCs [LT-HSCs]) compared with differentiated hematopoietic cells. Isolation of BM cells based solely on syndecan-2 surface expression produced a 24-fold enrichment for LT-HSCs and sixfold enrichment for α-catulin+c-kit+ HSCs, and yielded HSCs with superior in vivo repopulating capacity compared with CD150+ cells. Competitive repopulation assays revealed the HSC frequency to be 17-fold higher in syndecan-2+CD34-KSL cells compared with syndecan-2-CD34-KSL cells and indistinguishable from CD150+CD34-KSL cells. Syndecan-2 expression also identified nearly all repopulating HSCs within the CD150+CD34-KSL population. Mechanistically, syndecan-2 regulates HSC repopulating capacity through control of expression of Cdkn1c (p57) and HSC quiescence. Loss of syndecan-2 expression caused increased HSC cell cycle entry, downregulation of Cdkn1c, and loss of HSC long-term repopulating capacity. Syndecan-2 is a novel marker of HSCs that regulates HSC repopulating capacity via control of HSC quiescence.

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