Systemic approaches using single cell transcriptome reveal that C/EBPγ regulates autophagy under amino acid starved condition
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Systemic approaches using single cell transcriptome reveal that C/EBPγ regulates autophagy under amino acid starved condition. / Kim, Dongha; Kim, Junil; Yu, Young Suk; Kim, Yong Ryoul; Baek, Sung Hee; Won, Kyoung Jae.
I: Nucleic Acids Research, Bind 50, Nr. 13, 2022, s. 7298-7309.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Systemic approaches using single cell transcriptome reveal that C/EBPγ regulates autophagy under amino acid starved condition
AU - Kim, Dongha
AU - Kim, Junil
AU - Yu, Young Suk
AU - Kim, Yong Ryoul
AU - Baek, Sung Hee
AU - Won, Kyoung Jae
N1 - Publisher Copyright: © The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.
PY - 2022
Y1 - 2022
N2 - Autophagy, a catabolic process to remove unnecessary or dysfunctional organelles, is triggered by various signals including nutrient starvation. Depending on the types of the nutrient deficiency, diverse sensing mechanisms and signaling pathways orchestrate for transcriptional and epigenetic regulation of autophagy. However, our knowledge about nutrient type-specific transcriptional regulation during autophagy is limited. To understand nutrient type-dependent transcriptional mechanisms during autophagy, we performed single cell RNA sequencing (scRNAseq) in the mouse embryonic fibroblasts (MEFs) with or without glucose starvation (GS) as well as amino acid starvation (AAS). Trajectory analysis using scRNAseq identified sequential induction of potential transcriptional regulators for each condition. Gene regulatory rules inferred using TENET newly identified CCAAT/enhancer binding protein γ (C/EBPγ) as a regulator of autophagy in AAS, but not GS, condition, and knockdown experiment confirmed the TENET result. Cell biological and biochemical studies validated that activating transcription factor 4 (ATF4) is responsible for conferring specificity to C/EBPγ for the activation of autophagy genes under AAS, but not under GS condition. Together, our data identified C/EBPγ as a previously unidentified key regulator under AAS-induced autophagy.
AB - Autophagy, a catabolic process to remove unnecessary or dysfunctional organelles, is triggered by various signals including nutrient starvation. Depending on the types of the nutrient deficiency, diverse sensing mechanisms and signaling pathways orchestrate for transcriptional and epigenetic regulation of autophagy. However, our knowledge about nutrient type-specific transcriptional regulation during autophagy is limited. To understand nutrient type-dependent transcriptional mechanisms during autophagy, we performed single cell RNA sequencing (scRNAseq) in the mouse embryonic fibroblasts (MEFs) with or without glucose starvation (GS) as well as amino acid starvation (AAS). Trajectory analysis using scRNAseq identified sequential induction of potential transcriptional regulators for each condition. Gene regulatory rules inferred using TENET newly identified CCAAT/enhancer binding protein γ (C/EBPγ) as a regulator of autophagy in AAS, but not GS, condition, and knockdown experiment confirmed the TENET result. Cell biological and biochemical studies validated that activating transcription factor 4 (ATF4) is responsible for conferring specificity to C/EBPγ for the activation of autophagy genes under AAS, but not under GS condition. Together, our data identified C/EBPγ as a previously unidentified key regulator under AAS-induced autophagy.
U2 - 10.1093/nar/gkac593
DO - 10.1093/nar/gkac593
M3 - Journal article
C2 - 35801910
AN - SCOPUS:85134855306
VL - 50
SP - 7298
EP - 7309
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 13
ER -
ID: 315389047