Apr 21, 2017

iPSC-Derived Human Microglia-like Cells to Study Neurological Diseases

Neuron
Edsel M AbudMathew Blurton-Jones

Abstract

Microglia play critical roles in brain development, homeostasis, and neurological disorders. Here, we report that human microglial-like cells (iMGLs) can be differentiated from iPSCs to study their function in neurological diseases, like Alzheimer's disease (AD). We find that iMGLs develop in vitro similarly to microglia in vivo, and whole-transcriptome analysis demonstrates that they are highly similar to cultured adult and fetal human microglia. Functional assessment of iMGLs reveals that they secrete cytokines in response to inflammatory stimuli, migrate and undergo calcium transients, and robustly phagocytose CNS substrates. iMGLs were used to examine the effects of Aβ fibrils and brain-derived tau oligomers on AD-related gene expression and to interrogate mechanisms involved in synaptic pruning. Furthermore, iMGLs transplanted into transgenic mice and human brain organoids resemble microglia in vivo. Together, these findings demonstrate that iMGLs can be used to study microglial function, providing important new insight into human neurological disease.

  • References
  • Citations43

References

  • We're still populating references for this paper, please check back later.

Mentioned in this Paper

Study
Familial Alzheimer Disease (FAD)
In Vivo
Calcium [EPC]
Calcium
Brain
Human Induced Pluripotent Stem Cells
House mice
Alzheimer's Disease
Gene Expression

Related Feeds

Brain Organoids in Disease Modeling

Brain organoids are used to represent an in vitro model of the human brain. These brain organoids are derived from three-dimensional human pluripotent stem cells and can be used to help study brain biology, early brain development and different brain diseases. Discover the latest research on brain organoids in disease modeling here.

Alzheimer's Disease: APP

Amyloid precursor protein proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques. Here is the latest research.

Cell Adhesion Molecules in the Brain

Cell adhesion molecules found on cell surface help cells bind with other cells or the extracellular matrix to maintain structure and function. Here is the latest research on their role in the brain.

Alzheimer's Disease: Transcription

Transcription involves copying (transcribing) the gene's DNA sequence into RNA. Impaired transcription is associated with the pathogenesis and progression of conditions such as Alzheimer's disease (AD). Here are the latest discoveries pertaining to transcription and this disease.

Alzheimer's Disease: Animal models

Alzheimer's disease is a chronic neurodegenerative disease which can be studied using various experimental systems. This feed focuses on animal models used for Alzheimer's disease research.

Alzheimer's Disease: Tau & TDP-43

Alzheimer's disease is a chronic neurodegenerative disease. This feed focuses on the underlying role of Tau proteins and TAR DNA-binding protein 43, as well as other genetic factors, in Alzheimer's.

Alzheimer's Disease: Abeta

Alzheimer's disease (AD) is a chronic neurodegenerative disease associated with accumulation of amyloid plaques, which are comprised of amyloid beta. Here is the latest research in this field.

Alzheimer's Disease: Genes&Microglia

Genes and microglia are associated with the risk of developing and the progression of conditions such as Alzheimer's Disease (AD). Here are the latest discoveries pertaining to this disease.

Brain developing: Influences & Outcomes

This feed focuses on influences that affect the developing brain including genetics, fetal development, prenatal care, and gene-environment interactions. Here is the latest research in this field.