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Related Concept Videos

Organization of the Nervous System01:13

Organization of the Nervous System

The nervous system is one of the most complex systems in our body. It is organized into two main divisions: the central nervous system (CNS) and the peripheral nervous system (PNS).
The CNS, comprising the brain and spinal cord, houses billions of neurons. The brain is housed in the skull, while the spinal cord is linked to the brain through the foramen magnum of the occipital bone and is surrounded by the protective structure of the vertebral column. It is responsible for processing various...
Anatomy of the Brain: Major Regions01:20

Anatomy of the Brain: Major Regions

The brain is the most complex organ in the human body. It consists of four main parts: the cerebrum, diencephalon, cerebellum, and brainstem.
The cerebrum is the largest section of the brain and divides into left and right hemispheres, separated by a deep fissure. The cerebral outer layer of grey matter — the cerebral cortex — comprises elevations called gyri and shallow groves called sulci. The inner portion of white matter includes long nerve fibers known as axons, which connect various areas...
Cerebrum: Anatomical Overview II01:11

Cerebrum: Anatomical Overview II

Each cerebral hemisphere can be divided into three main regions. The outermost region, the cerebral cortex, is a thin layer (2 to 4 millimeters thick) made up of gray matter, consisting of neuron cell bodies, dendrites, glial cells, and blood vessels. The middle region, or white matter, is primarily composed of myelinated nerve fibers organized into three types of large tracts: association fibers, commissures, and projection fibers. Association fibers connect different areas within the same...
Functional Brain Systems: Limbic System01:15

Functional Brain Systems: Limbic System

The limbic system, often called the "emotional brain," is a complex set of structures located deep within the brain. The intricate network of the limbic system supports a wide range of psychological functions, from emotional regulation to memory formation and sensory processing. This functional brain region encompasses specific parts of the diencephalon and the cerebrum, integrating the higher mental functions of the cerebral cortex with the primitive emotional responses of the deep brain...
Functional Brain Systems: Reticular Formation01:13

Functional Brain Systems: Reticular Formation

The reticular formation is a complex network of gray and white matter located within the brainstem extending from the medulla to the midbrain.
Within the reticular formation, there are several distinct nuclei that can be classified into three broad categories. The Raphe nuclei are located along the midline of the brainstem. They are primarily known for their role in synthesizing and releasing serotonin, a neurotransmitter involved in regulating mood, appetite, sleep, and circadian rhythms. The...
Organization of the Brain01:30

Organization of the Brain

The brain is an integral component of the nervous system and serves as the center for processing sensory inputs, making decisions, and directing bodily actions. This complex organ is organized into three primary sections: the hindbrain, midbrain, and forebrain, each responsible for a range of vital functions.
Hindbrain
The hindbrain, located at the base of the brain, plays a vital role in regulating automatic processes that sustain life. It includes the medulla oblongata, which is essential for...

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Updated: Jun 15, 2026

Lineage Tracing and Clonal Analysis in Developing Cerebral Cortex Using Mosaic Analysis with Double Markers MADM
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Lineage Tracing and Clonal Analysis in Developing Cerebral Cortex Using Mosaic Analysis with Double Markers MADM

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Defined human tri-lineage brain microtissues.

Takeshi Uenaka1,2, Sascha Jung3, Ishan Kumar1,2

  • 1Institute for Stem Cell Biology & Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.

Biorxiv : the Preprint Server for Biology
|August 13, 2025
PubMed
Summary
This summary is machine-generated.

Human iPSC-derived microglia were co-cultured with neurons and astrocytes in novel brain microtissues. These microtissues promote homeostatic microglia phenotypes and model neurodegenerative diseases.

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Area of Science:

  • Neuroscience
  • Stem Cell Biology
  • Immunology

Background:

  • Microglia are central nervous system immune cells crucial for brain health and disease.
  • Human and mouse microglia differ significantly, necessitating human-specific models.
  • Existing models struggle to replicate human microglia's in vivo environment and interactions.

Purpose of the Study:

  • To develop a robust human iPSC-based brain microtissue model for studying microglia-neuron-astrocyte interactions.
  • To establish a system that supports homeostatic microglial phenotypes in vitro.
  • To investigate cell-cell communication networks and model neurodegenerative processes.

Main Methods:

  • Co-culture of human induced pluripotent stem cell (iPSC)-derived neurons, astrocytes, and microglia in 2D and 3D microtissues.
  • Cultivation in fully defined media without exogenous cytokines.
  • Analysis of cell morphology, function, survival, maturation, and gene expression via scRNA-seq and snRNA-seq.
  • Modeling of alpha-synuclein seeding and aggregation.

Main Results:

  • Developed stable, self-sufficient brain microtissues with characteristic cell morphologies and functions.
  • Co-cultured microglia exhibited homeostatic phenotypes, unlike those with exogenous cytokines.
  • Astrocytes, not neurons, were sufficient for microglial survival and maturation, with M-CSF being essential.
  • Identified reciprocal cell communication networks via multi-omic analyses.
  • Successfully recapitulated alpha-synuclein pathology in the microtissues.

Conclusions:

  • Human iPSC-derived brain microtissues provide a powerful platform for studying microglia in a homeostatic and disease context.
  • Astrocytes play a critical role in supporting microglial development and function.
  • These microtissues serve as valuable human cell models for neurodegenerative disease research.