Rare cells, transiently activate cell regeneration

People who often fish with earthworms as bait may be familiar with the regenerative ability of earthworms after cutting their heads or tails in half

How did this happen? What cell type contributes to this amazing ability to regenerate? In addition to stem cells, this is obviously important.

The latest research published by members of the Sánchez Alvarado laboratory of the Stowers Institute of Medical Research in Nature Cell Biology on September 2, 2021 provides some early answers to these complex questions

“We already know that wound-induced epidermis and wound-induced muscle play different roles in the regeneration process, but we want to understand the big picture,” explained lead author Dr.

"Before we know some important genes, regeneration is a bit like a black box.

Benham Pyle described the "dream experiment" and the task they ultimately accomplished to "characterize gene expression over time in all the different cell types of a regenerative animal at the single-cell level

At first, researchers considered using large-scale RNA sequencing for experiments.

But in early 2017, Sánchez Alvarado discovered a preprint that had just been released to bioRxiv and reported on a new single-cell sequencing method SplitSeq

After making it work, Benham Pyle and colleagues captured nearly 300,000 single-cell transcriptomes in 8 different tissues and stem cell compartments, and compared animals that were able to regenerate and animals that had lost the ability to regenerate

Benham Pyle explained: "This allows us to look at all the different types of cells in the entire animal body to see which cells respond to amputation and which genes mark these cells when these cells change and respond to regeneration

The researchers discovered and described five different cell types from three germ layers, which changed the transcription output instantaneously after amputation

Some of their findings were more unexpected than others

However, the researchers were surprised to find a rare cell, a state induced during systemic regeneration, called the transient regeneration activated cell state (TRACS), and found that the intestine seems to regulate stem cell maintenance and tissue remodeling after amputation All are important

Benham Pyle said: "I didn't expect that the intestine would completely change its output and reshape its function after injury

Obtaining and understanding data is a team work
.

"During the epidemic, we revised the manuscript while losing 50% of our research capabilities," Benham-Pyle said
.
"Sean McKinney and the Microscopy Center have found a way to automate imaging.
We have developed a system in which I can give them 40 to 80 slides at a time, including all the different samples and RNAi conditions, to image during the night operation.

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They can generate terabytes of imaging data for us on a scanning confocal microscope, which helps us get the huge improvement needed to accept papers
.
They set a very high standard for microscope equipment
.
"

The other co-author of the study was Carolyn E.
Brewster, a bioinformatics expert, who helped analyze the data generated by the experiment and helped create a website related to the paper; Aubrey M.
Kent, who helped describe the first from the data set Batch RNAi phenotype (she is now tracking and discovering some epidermal genes that affect the stem cell compartment); Dr.
Frederick G.
Mann helped clone many genes screened and identified by Benham-Pyle in the paper;

Taking a step back and saying, "What this paper does is to look at what kind of cells need to be in a signal environment from a global perspective to stimulate stem cells to create new tissues and replace missing tissues," Benham Pyle reflects
.

"It turns out that some of the genes we identified, such as in the intestine, are also related to immune evasion or wound healing in cancer
.
Many of the mechanisms that stem cells use to escape the immune system and promote proliferation and growth during the regeneration process may be related to the tumor's choice.
The mechanism is the same
.
By understanding which non-stem cell states and tissue types help create this signal environment, we may finally find new targets to stimulate healthy and normal wound healing with limited regenerative capacity, or limit our unwilling growth The growth capacity of things (such as tumors)
.
"

"Now that we have a map, we can figure out how these cells communicate with each other, what they are doing, and how they do it
.
"