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BACH1 changes microglial metabolism and affects astrogenesis during mouse brain development.

Yanyan Wang | Wenwen Wang | Libo Su | Fen Ji | Mengtian Zhang | Yanzhen Xie | Tianyu Zhang | Jianwei Jiao
Developmental cell | 2024

Microglia are highly heterogeneous as resident immune cells in the central nervous system. Although the proinflammatory phenotype of microglia is driven by the metabolic transformation in the disease state, the mechanism of metabolic reprogramming in microglia and whether it affects surrounding astrocyte progenitors have not been well elucidated. Here, we illustrate the communication between microglial metabolism and astrogenesis during embryonic development. The transcription factor BTB and CNC homology 1 (Bach1) reduces lactate production by inhibiting two key enzymes, HK2 and GAPDH, during glycolysis. Metabolic perturbation of microglia reduces lactate-dependent histone modification enrichment at the Lrrc15 promoter. The microglia-derived LRRC15 interacts with CD248 to participate in the JAK/STAT pathway and influence astrogenesis. In addition, Bach1cKO-Cx3 mice exhibit abnormal neuronal differentiation and anxiety-like behaviors. Altogether, this work suggests that the maintenance of microglia metabolic homeostasis during early brain development is closely related to astrogenesis, providing insights into astrogenesis and related diseases.

Pubmed ID: 38101413 RIS Download

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PE anti-mouse CD45 (antibody)

RRID:AB_312970

This monoclonal targets CD45

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Stat3 (79D7) Rabbit mAb (antibody)

RRID:AB_331269

This recombinant monoclonal targets Stat3

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Phospho-Stat3 (Tyr705) (D3A7) XP Rabbit mAb (antibody)

RRID:AB_2491009

This monoclonal targets Phospho-Stat3 (Tyr705)

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Lactyl-Histone H3 (Lys18) Rabbit mAb (antibody)

RRID:AB_2909438

This recombinant monoclonal targets Lactyl-Histone H3 (Lys18)

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Anti-L-lactyllysine rabbit pAb (antibody)

RRID:AB_2868521

This polyclonal targets lactyllysine

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HA-Tag (C29F4) Rabbit mAb (antibody)

RRID:AB_1549585

This monoclonal targets HA-Tag

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Beta Actin antibody (antibody)

RRID:AB_10700003

This polyclonal targets Beta Actin

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Beta Actin antibody (antibody)

RRID:AB_2289225

This monoclonal targets Beta Actin

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P2Y12/P2RY12 Antibody (antibody)

RRID:AB_2810254

This polyclonal targets P2Y12/P2RY12

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CX3CR1 antibody (antibody)

RRID:AB_306203

This polyclonal targets CX3CR1

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GLAST antibody (antibody)

RRID:AB_2878738

This polyclonal targets GLAST

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BACH1 (F-9) (antibody)

RRID:AB_10608972

This monoclonal targets BACH1 (F-9)

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BACH1 Polyclonal Antibody (antibody)

RRID:AB_2766202

This polyclonal targets BACH1

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Rabbit Anti-BLBP Polyclonal Antibody, Unconjugated (antibody)

RRID:AB_880078

This polyclonal targets BLBP - Neuronal Marker

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Anti Iba1, Rabbit antibody (antibody)

RRID:AB_839504

This polyclonal targets Iba1

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Iba1 antibody (antibody)

RRID:AB_2224402

This polyclonal targets AIF1

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FVB-Tg(GFAP-cre)25Mes/J (organism)

RRID:IMSR_JAX:004600

Mus musculus with name FVB-Tg(GFAP-cre)25Mes/J from IMSR.

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B6.129P2(Cg)-Cx3cr1tm1Litt/J (organism)

RRID:IMSR_JAX:005582

Mus musculus with name B6.129P2(Cg)-Cx3cr1tm1Litt/J from IMSR.

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B6J.B6N(Cg)-Cx3cr1tm1.1(cre)Jung/J (organism)

RRID:IMSR_JAX:025524

Mus musculus with name B6J.B6N(Cg)-Cx3cr1tm1.1(cre)Jung/J from IMSR.

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Neuro-2a (cell line)

RRID:CVCL_0470

Cell line Neuro-2a is a Cancer cell line with a species of origin Mus musculus

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HEK293 (cell line)

RRID:CVCL_0045

Cell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)

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