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BACH1 changes microglial metabolism and affects astrogenesis during mouse brain development

Yanyan Wang1, Wenwen Wang2, Libo Su1

  • 1State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Beijing Institute for Stem Cell and Regenerative Medicine, Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China.

Developmental Cell
|December 15, 2023
PubMed

Insights

Microglia metabolism impacts brain development. Bach1 maintains microglial metabolic homeostasis, influencing astrogenesis and neuronal differentiation, crucial for preventing neurodevelopmental disorders.

Area of Science:

  • Neuroscience
  • Immunology
  • Developmental Biology

Background:

  • Microglia, the resident immune cells of the central nervous system, exhibit significant heterogeneity.
  • Microglial metabolic reprogramming is linked to proinflammatory states in disease, but its role in embryonic development and influence on astrogenesis remain unclear.

Purpose of the Study:

  • To elucidate the communication between microglial metabolism and astrogenesis during embryonic brain development.
  • To investigate the role of the transcription factor Bach1 in regulating microglial metabolism and its downstream effects.

Main Methods:

  • Analysis of microglial glycolysis and lactate production, focusing on enzymes HK2 and GAPDH.
  • Investigation of the interaction between microglia-derived LRRC15 and CD248 in the JAK/STAT pathway.
  • Utilizing Bach1 conditional knockout (cKO) mice (Bach1cKO-Cx3) to assess in vivo effects.

Main Results:

  • Bach1 inhibits glycolysis by suppressing HK2 and GAPDH, reducing microglial lactate production.
  • Metabolic changes in microglia alter histone modifications at the Lrrc15 promoter.
  • Microglia-derived LRRC15, via CD248 and the JAK/STAT pathway, influences astrogenesis.
  • Bach1 deficiency in microglia leads to abnormal neuronal differentiation and anxiety-like behaviors in mice.

Conclusions:

  • Microglial metabolic homeostasis is critical for proper astrogenesis during early brain development.
  • Dysregulation of microglial metabolism can impact neuronal development and behavior.
  • This study provides novel insights into the interplay between microglia and astrocytes, relevant to neurodevelopmental disorders.
Keywords:
BACH1LRRC15astrogenesishistone lactylationmicroglia metabolism

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