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C4 Pathway and CAM

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Most plants use the C3 pathway for carbon fixation. However, some plants, such as sugar cane, corn, and cacti that grow in hot conditions, use alternative pathways to fix carbon and conserve energy loss due to photorespiration. Photorespiration is the process that occurs when the oxygen concentration is high. Under such conditions, the rubisco enzyme in the Calvin cycle binds O2 instead of CO2, which halts photosynthesis and consumes energy.
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Flow Cytometry-based Drug Screening System for the Identification of Small Molecules That Promote Cellular Differentiation of Glioblastoma Stem Cells

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Published on: January 10, 2018

Small-molecule screen reveals pathways that regulate C4 secretion in stem cell-derived astrocytes.

Francesca Rapino¹, Ted Natoli², Francesco Limone³

¹Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Stem Cell Reports

|December 23, 2022

Summary

Researchers identified pathways regulating complement component 4 (C4) production in astrocytes, crucial for brain immune responses and linked to schizophrenia risk. This discovery aids developing new therapies for central nervous system (CNS) diseases.

Keywords:

C4 CMap ELISA-based screen ESCs L1000 astrocytes complement component C4 complement system connectivity map disease modeling human embryonic stem cells human induced pluripotent stem cells iPSCs screen stem cell-derived astrocytes

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Visualizing and Analyzing Intracellular Transport of Organelles and Other Cargos in Astrocytes

Visualizing and Analyzing Intracellular Transport of Organelles and Other Cargos in Astrocytes

Published on: August 28, 2019

Area of Science:

Neuroscience
Immunology
Genetics

Background:

The brain's complement system is vital for immune response and synaptic pruning in development and disease.
Complement component 4 (C4) is implicated in schizophrenia risk, highlighting the need to understand its regulation.

Purpose of the Study:

To identify pathways that modulate the production of complement component 4 (C4) in astrocytes.
To develop a disease-relevant assay for screening small molecules affecting C4 secretion.

Main Methods:

Developed a 3D protocol for generating large numbers of astrocytes from pluripotent cells.
Performed transcriptional profiling to characterize astrocyte populations.
Utilized an ELISA-based small-molecule screen to identify modulators of C4 secretion.
Constructed a connectivity map to predict and validate regulatory pathways, including c-Jun-kinase.

Main Results:

Successfully generated homogeneous populations of dorsal fetal-like astrocytes.
Identified epigenetic regulators and intracellular signaling pathway inhibitors that modulate astrocyte C4 secretion.
Validated key regulatory pathways, notably one involving c-Jun-kinase.

Conclusions:

This study establishes a foundation for understanding and targeting complement cascade pathways in CNS diseases.
Findings pave the way for developing novel therapeutic strategies for conditions involving C4 dysregulation, such as schizophrenia.