Toll-Like Receptor 5 Promotes the Neurogenesis From Embryonic Stem Cells and Adult Hippocampal Neural Stem Cells in Mice

Kyung-Joo Seong; Seungho Choi; Hyun-Gwan Lee; Joon Haeng Rhee; Jin Ho Lee; Jeong-Tae Koh; Sun-Hun Kim; Won-Seok Choi; Ji-Yeon Jung; Won-Jae Kim

doi:10.1093/stmcls/sxab025

Toll-Like Receptor 5 Promotes the Neurogenesis From Embryonic Stem Cells and Adult Hippocampal Neural Stem Cells in Mice

Stem Cells. 2022 Mar 31;40(3):303-317. doi: 10.1093/stmcls/sxab025.

Authors

Affiliations

¹ Dental Science Research Institute, Hard-tissue Biointerface Research Center, Department of Oral Physiology, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.
² Department of Oceanography, Marine Ecological Disturbing and Harmful Organisms Research Center, BK21+ Climate Change and Coastal Ecosystem Prediction Research Center, Chonnam National University, Gwangju, Republic of Korea.
³ National Research Laboratory of Molecular Microbial Pathogenesis, Research Institute of Vibrio Infection and Genome Research Center for Enteropathogenic Bacteria, Department of Microbiology, Chonnam National University Medical School, Gwangju, Republic of Korea.
⁴ School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea.
⁵ Dental Science Research Institute, Hard-tissue Biointerface Research Center, Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.
⁶ Dental Science Research Institute, Hard-tissue Biointerface Research Center, Department of Oral Anatomy, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.

PMID: 35304896
DOI: 10.1093/stmcls/sxab025

Abstract

Toll-like receptors (TLRs) make a crucial contribution to the innate immune response. TLR5 was expressed in embryoid body derived from mouse embryonic stem cells (mESCs) and βIII-tubulin-positive cells under all-trans retinoic acid-treated condition. TLR5 was upregulated during neural differentiation from mESCs and augmented the neural differentiation of mESCs via nuclear factor-κB and interleukin 6/CREB pathways. Besides, TLR5 was expressed in SOX2- or doublecortin-positive cells in the subgranular zone of the hippocampal dentate gyrus where adult neurogenesis occurs. TLR5 inhibited the proliferation of adult hippocampal neural stem cells (NSCs) by regulating the cell cycle and facilitated the neural differentiation from the adult hippocampal NSCs via JNK pathway. Also, TLR5 deficiency impaired fear memory performance in mice. Our data suggest that TLR5 is a crucial modulator of neurogenesis from mESCs and adult hippocampal NSCs in mice and represents a new therapeutic target in neurological disorders related to cognitive function.

Keywords: adult stem cells; animal models; cell culture; nervous system; neural differentiation; neural stem cells (NSCs); neuron.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Proliferation
Embryonic Stem Cells / metabolism
Hippocampus
Mice
Mice, Inbred C57BL
Neural Stem Cells* / metabolism
Neurogenesis / physiology
Toll-Like Receptor 5* / metabolism

Substances

Tlr5 protein, mouse
Toll-Like Receptor 5