TY - JOUR
T1 - Lack of a site-specific phosphorylation of Presenilin 1 disrupts microglial gene networks and progenitors during development
AU - Ledo, Jose Henrique
AU - Zhang, Ran
AU - Mesin, Luka
AU - Mourão-Sá, Diego
AU - Azevedo, Estefania P.
AU - Troyanskaya, Olga G.
AU - Bustos, Victor
AU - Greengard, Paul
PY - 2020/8
Y1 - 2020/8
N2 - Microglial cells play a key role in brain homeostasis from development to adulthood. Here we show the involvement of a site-specific phosphorylation of Presenilin 1 (PS1) in microglial development. Profiles of microglia-specific transcripts in different temporal stages of development, combined with multiple systematic transcriptomic analysis and quantitative determination of microglia progenitors, indicate that the phosphorylation of PS1 at serine 367 is involved in the temporal dynamics of microglial development, specifically in the developing brain rudiment during embryonic microgliogenesis. We constructed a developing brain-specific microglial network to identify transcription factors linked to PS1 during development. Our data showed that PS1 functional connections appear through interaction hubs at Pu.1, Irf8 and Rela-p65 transcription factors. Finally, we showed that the total number of microglia progenitors was markedly reduced in the developing brain rudiment of embryos lacking PS1 phosphorylation compared to WT. Our work identifies a novel role for PS1 in microglial development.
AB - Microglial cells play a key role in brain homeostasis from development to adulthood. Here we show the involvement of a site-specific phosphorylation of Presenilin 1 (PS1) in microglial development. Profiles of microglia-specific transcripts in different temporal stages of development, combined with multiple systematic transcriptomic analysis and quantitative determination of microglia progenitors, indicate that the phosphorylation of PS1 at serine 367 is involved in the temporal dynamics of microglial development, specifically in the developing brain rudiment during embryonic microgliogenesis. We constructed a developing brain-specific microglial network to identify transcription factors linked to PS1 during development. Our data showed that PS1 functional connections appear through interaction hubs at Pu.1, Irf8 and Rela-p65 transcription factors. Finally, we showed that the total number of microglia progenitors was markedly reduced in the developing brain rudiment of embryos lacking PS1 phosphorylation compared to WT. Our work identifies a novel role for PS1 in microglial development.
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U2 - 10.1371/journal.pone.0237773
DO - 10.1371/journal.pone.0237773
M3 - Article
C2 - 32822378
AN - SCOPUS:85089799174
VL - 15
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 8 August 2020
M1 - e0237773
ER -