Fate Mapping with CRISPR
Last Wednesday I attended a talk on Fate Mapping, which in the study of genomics means finding out the cell lineage of every adult organ which makes up an organism. What is the cell lineage? It is about tracking which cells split to form other cells to discover how all the organs are interrelated.
This is done by creating a cell tree, much like a family tree if you wanted to discover your ancestry. In ye olden days of science, this meant sitting in a lab, staring into a microscope for hours, tracking the cell divisions, while writing out the chart by hand. You would spend hours watching the cells as they divided, then divided again. Of course, this is easiest when the organism you are observing is transparent. It was decidedly more difficult to observe organism which were opaque.
Which is where CRISPR comes in. CRISPR is being used to shed some light on those hard to trace divisions in opaque creatures, such as zebrafish. CRISPR and CAS9 is something which exists in nature – primarily it is the immune system in bacteria which cuts up invading DNA. Scientists have repurposed CAS9 as a scissors to snip the DNA in say, a zebrafish. But, CAS9 is useless without something telling it to make the cuts – in this case guide RNA which targets specific areas of the DNA.
CAS9 is just a tool, like any other. It cannot add anything to the genome, just cut it, over and over and over at the same place. Much like a broken record will play the same notes over and over and over again. And this constant cutting is actually what the scientists want.
As CAS9 cuts the DNA, the cell's RNA will fix it, but sometimes, it makes mistakes - what you'd think of as mutations. And those mutations are important, but not for the reasons you'd think. There are two types of mutations, one is the insertion of base pairs, sort of like if the RNA forgot where it was in a book and ended up reading a paragraph over, the other is the deletion of base pairs, where the RNA will skip a bit before it continues making copies. The pattern of these mutations in the cells' DNA acts as a barcode, letting the scientists know when certain cells split off to form different organs, and by tracing these mutations back, they can build a cell tree.
So far I only know of zebrafish which have been mapped this way. And it is illegal to use CRISPR and CAS9 on humans.
This is done by creating a cell tree, much like a family tree if you wanted to discover your ancestry. In ye olden days of science, this meant sitting in a lab, staring into a microscope for hours, tracking the cell divisions, while writing out the chart by hand. You would spend hours watching the cells as they divided, then divided again. Of course, this is easiest when the organism you are observing is transparent. It was decidedly more difficult to observe organism which were opaque.
Which is where CRISPR comes in. CRISPR is being used to shed some light on those hard to trace divisions in opaque creatures, such as zebrafish. CRISPR and CAS9 is something which exists in nature – primarily it is the immune system in bacteria which cuts up invading DNA. Scientists have repurposed CAS9 as a scissors to snip the DNA in say, a zebrafish. But, CAS9 is useless without something telling it to make the cuts – in this case guide RNA which targets specific areas of the DNA.
CAS9 is just a tool, like any other. It cannot add anything to the genome, just cut it, over and over and over at the same place. Much like a broken record will play the same notes over and over and over again. And this constant cutting is actually what the scientists want.
As CAS9 cuts the DNA, the cell's RNA will fix it, but sometimes, it makes mistakes - what you'd think of as mutations. And those mutations are important, but not for the reasons you'd think. There are two types of mutations, one is the insertion of base pairs, sort of like if the RNA forgot where it was in a book and ended up reading a paragraph over, the other is the deletion of base pairs, where the RNA will skip a bit before it continues making copies. The pattern of these mutations in the cells' DNA acts as a barcode, letting the scientists know when certain cells split off to form different organs, and by tracing these mutations back, they can build a cell tree.
So far I only know of zebrafish which have been mapped this way. And it is illegal to use CRISPR and CAS9 on humans.
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Enduring Ephemera
I collect random historical facts and obscure bits of information like a dragon collects gold. Here is where I dispense those nuggets of wisdom.
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