TY - JOUR
T1 - Adult neural stem cells have latent inflammatory potential that is kept suppressed by Tcf4 to facilitate adult neurogenesis
AU - Shariq, Mohammad
AU - Sahasrabuddhe, Vinaya
AU - Krishna, Sreevatsan
AU - Radha, Swathi
AU - Nruthyathi,
AU - Bellampalli, Ravishankara
AU - Dwivedi, Anukriti
AU - Cheramangalam, Rajit
AU - Reizis, Boris
AU - Hébert, Jean
AU - Ghosh, Hiyaa S.
N1 - Publisher Copyright:
Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
PY - 2021/5
Y1 - 2021/5
N2 - 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.
AB - 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.
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U2 - 10.1126/sciadv.abf5606
DO - 10.1126/sciadv.abf5606
M3 - Article
C2 - 34020954
AN - SCOPUS:85106515705
SN - 2375-2548
VL - 7
JO - Science Advances
JF - Science Advances
IS - 21
M1 - eabf5606
ER -