Scientists have devised a mouse model that lets researchers track every cell in the body, from the embryonic stage until adulthood. Using a "barcoding" technique and CRISPR gene editing technology, the model can identify different cell types as they emerge and what genes each is turning on. Described in the journal Cell, the system is the first of its kind and should yield a greater understanding of development, aging, and disease.
"The dream that many developmental biologists have had for decades is a way to reconstruct every single cell lineage, cell-by-cell, as an embryo develops, or as a tissue is built up," says the co-senior author on the paper. "We could use this mouse model to follow its entire development."
The authors created the mouse model using a method they call CRISPR Array Repair Lineage tracing, or CARLIN. The model can reveal cell lineages -- the "family tree" in which parent cells create different types of daughter cells -- as well as what genes are turned on or off in every cell over time.
Previously, scientists have only been able to trace small groups of cells in mice using dyes or fluorescent markers. Tags or barcodes have also been used, but previous approaches required prior knowledge of markers to isolate different cell types, or required time-consuming extraction and manipulation of cells, which could affect their properties. The advent of CRISPR has enabled researchers to barcode cells without perturbing the cells and to follow the lineage of thousands of cells simultaneously.
Using an inducible form of CRISPR, the researchers can create up to 44,000 different identifying barcodes at any time point in a mouse's lifespan. The scientists can then read out the barcodes using another technology called single cell RNA sequencing, enabling collection of information on thousands of genes that are turned on in each barcoded cell. This, in turn, provides information about the cells' identity and function.
As a test case, the researchers used the new system to reveal unknown aspects of blood development during embryonic development, and to observe the dynamics of blood replenishment after chemotherapy in adult mice.
But the researchers believe their system could also be used to understand the changes in cellular lineage trees during disease and aging. Additionally, the system could be used to record the response to environmental stimuli like pathogen exposure and nutrient intake.
"Being able to create single-cell lineage maps of mammalian tissues is unprecedented," says the co-senior author. "Besides its many applications to studying developmental biology, our model will provide important insight on the cell types and hierarchies that are affected as organisms respond to injury and disease."
https://www.cell.com/cell/pdf/S0092-8674(20)30554-7.pdf?
CRISPR barcoding of cells to track an organism's development
- 1,661 views
- Added
Edited
Latest News
Abusive drugs hijack natura…
By newseditor
Posted 23 Apr
Mechanism of action of the…
By newseditor
Posted 23 Apr
Role of fat in rare neurolo…
By newseditor
Posted 23 Apr
How protein synthesis in de…
By newseditor
Posted 22 Apr
Atlas of mRNA variants in d…
By newseditor
Posted 22 Apr
Other Top Stories
New SARS-like virus can jump directly from bats to humans, no treat…
Read more
Developing universal antibody for alphaviruses
Read more
Mutation in coronavirus protein reduces its neurovirulence
Read more
Using copper to prevent the spread of respiratory viruses
Read more
How does human enterovirus D68 enters the cell?
Read more
Protocols
A programmable targeted pro…
By newseditor
Posted 23 Apr
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Publications
Exploiting pancreatic cance…
By newseditor
Posted 23 Apr
Structure of antiviral drug…
By newseditor
Posted 23 Apr
Type-I-interferon-responsiv…
By newseditor
Posted 23 Apr
Selenium, diabetes, and the…
By newseditor
Posted 23 Apr
Long-term neuropsychologica…
By newseditor
Posted 23 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar