The thrombin receptor restricts subventricular zone neural stem cell expansion and differentiation

Chan Il Choi, Hyesook Yoon, Kristen L. Drucker, Monica R. Langley, Laurel Kleppe, Isobel A Scarisbrick

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Thrombin is frequently increased in the CNS after injury yet little is known regarding its effects on neural stem cells. Here we show that the subventricular zone (SVZ) of adult mice lacking the high affinity receptor for thrombin, proteinase activated receptor 1 (PAR1), show increased numbers of Sox2+ and Ki-67+ self-renewing neural stem cells (NSCs) and Olig2+ oligodendrocyte progenitors. SVZ NSCs derived from PAR1-knockout mice, or treated with a PAR1 small molecule inhibitor (SCH79797), exhibited enhanced capacity for self-renewal in vitro, including increases in neurosphere formation and BrdU incorporation. PAR1-knockout SVZ monolayer cultures contained more Nestin, NG2+ and Olig2+ cells indicative of enhancements in expansion and differentiation towards the oligodendrocyte lineage. Cultures of NSCs lacking PAR1 also expressed higher levels of myelin basic protein, proteolipid protein and glial fibrillary acidic protein upon differentiation. Complementing these findings, the corpus callosum and anterior commissure of adult PAR1-knockout mice contained greater numbers of Olig2+ progenitors and CC1+ mature oligodendrocytes. Together these findings highlight PAR1 inhibition as a means to expand adult SVZ NSCs and to promote an increased number of mature myelinating oligodendrocytes in vivo that may be of particular benefit in the context of neural injury where PAR1 agonists such as thrombin are deregulated.

Original languageEnglish (US)
Article number9360
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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PAR-1 Receptor
Thrombin Receptors
Neural Stem Cells
Lateral Ventricles
Cell Differentiation
Oligodendroglia
Knockout Mice
Thrombin
Proteolipids
Nestin
Myelin Basic Protein
Corpus Callosum
Glial Fibrillary Acidic Protein
Wounds and Injuries
Bromodeoxyuridine

ASJC Scopus subject areas

  • General

Cite this

The thrombin receptor restricts subventricular zone neural stem cell expansion and differentiation. / Choi, Chan Il; Yoon, Hyesook; Drucker, Kristen L.; Langley, Monica R.; Kleppe, Laurel; Scarisbrick, Isobel A.

In: Scientific Reports, Vol. 8, No. 1, 9360, 01.12.2018.

Research output: Contribution to journalArticle

Choi, Chan Il ; Yoon, Hyesook ; Drucker, Kristen L. ; Langley, Monica R. ; Kleppe, Laurel ; Scarisbrick, Isobel A. / The thrombin receptor restricts subventricular zone neural stem cell expansion and differentiation. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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