Adult neural stem cells have latent inflammatory potential that is kept suppressed by Tcf4 to facilitate adult neurogenesis

Mohammad Shariq, Vinaya Sahasrabuddhe, Sreevatsan Krishna, Swathi Radha, Nruthyathi, Ravishankara Bellampalli, Anukriti Dwivedi, Rajit Cheramangalam, Boris Reizis, Jean Hébert, Hiyaa S. Ghosh

Research output: Contribution to journalArticlepeer-review

Abstract

Inflammation is known to adversely affect adult neurogenesis, wherein the source of inflammation is largely thought to be extraneous to the neurogenic niche. Here, we demonstrate that the adult hippocampal neural progenitors harbor an inflammatory potential that is proactively suppressed by transcription factor 4 (Tcf4). Deletion of Tcf4 in hippocampal nestin-expressing progenitors causes loss of proliferative capacity and acquisition of myeloid inflammatory properties. This transformation abolishes their differentiation potential and causes production of detrimental factors that adversely affect niche cells, causing inflammation in the dentate gyrus. Thus, on one hand, Tcf4 deletion causes abrogation of proliferative progenitors leading to reduction of adult neurogenesis, while on the other, their accompanying inflammatory transformation inflicts inflammation in the niche. Taken together, we provide the first evidence for a latent inflammatory potential of adult hippocampal neural progenitors and identify Tcf4 as a critical regulator that facilitates adult neurogenesis via proactive suppression of this detrimental potential.

Original languageEnglish (US)
Article numbereabf5606
JournalScience Advances
Volume7
Issue number21
DOIs
StatePublished - May 2021

ASJC Scopus subject areas

  • General

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