The hematopoietic system is responsible for the formation of all blood cell types from hematopoietic stem cells (immature cells that are able to mature into any type of blood cell). This is a key process for the immune system because it produces white blood cells (along with red blood cells and platelets). With this in mind, Rosental and colleagues set out to examine the hematopoietic system of a marine invertebrate, Botryllus schlosseri, also known as the golden star tunicate. Why? Tunicates are the closest living relative to vertebrates, meaning that we may be able to uncover secrets regarding how immune systems have changed and stayed the same throughout evolution, and even understand our own immune systems better!
An interesting feature of B. schlosseri tunicates is that genetically compatible organisms can fuse together and share a circulatory system (forming a parabiont). However, genetically dissimilar organisms will not recognize one another and will reject one another. This recognition is controlled by the gene bhf (Botryllus histocompatibility factor). The manner is which fusion (or rejection) of tunicate colonies takes place is still being investigated. Understanding the mechanism and details of fusion or rejection can, for example, aid our understanding of how human transplant organs are rejected by the immune system, hopefully leading to fewer organ rejections in the future.
In the Rosental et al., 2018 paper, the first step undertaken by researchers was understanding individual gene expression profiles of hematopoietic stem cell populations and comparing them to gene expression profiles of various mouse cell populations (specifically those with important immune system implications). As tunicates are the closest living relative to vertebrates, researchers wanted to understand if their hematopoietic stem cell populations are similar to those in mammals. If they are similar then tunicates may be used as a model to further understand mammalian hematopoietic stem cell populations. This would provide scientists with a relatively inexpensive model with many fewer research restrictions than using human subjects (since tunicates are invertebrates). Researchers uncovered that there was significant overlap in gene expression between three B. schlosseri hematopoietic stem cell populations (CP25, CP33, and CP34) and several mammalian cell populations with known importance to immune functions. This means that these three tunicate stem cell populations are worth investigating further, as these stem cell populations may be able to serve as a model in helping us understand more about our own immune systems.
The next step was to determine if certain B. schlosseri hematopoietic stem cell populations (again: CP25, CP33, and CP34) can differentiate into other cell types and to determine if they can undergo multilineage differentiation. In other words, aside from the gene signature, do they share other stem cell properties with mammalian cells? Through experimentation (transplanting cells from donor colonies to recipient colonies) it was determined that these stem cell populations can differentiate into other cell types and they can also undergo multilineage differentiation, just like mammalian cells!
The self-recognition abilities of this tunicate (whereby similar colonies can fuse and form parabionts while dissimilar colonies reject one another), are fascinating and have potential implications for increasing human transplant successes. Rosental and colleagues, therefore, wanted to investigate the effector mechanism behind this self-recognition. The immune effector mechanism of this cellular allogeneic (rejection to non-self tissues) response in B. schlosseri was shown to be cytotoxicity. This means that when one B. schlosseri tunicate colony comes into contact with a non-self colony, it initiates an immune response that damages and kills cells from the non-self colony. Interestingly, blocking bhf (the previously known “recognition” component of the Botryllus immune system) was shown to impact this cytotoxic reaction. Therefore, bhf was determined to be a major histocompatibility factor (way of recognizing particles from foreign/non-self bodies) essential to the process of self-recognition in these tunicates. Again, this process is similar to what we see in mammals.
What does it all mean? As it turns out, the immune system and hematopoietic system of golden star tunicates have some overlap with what we see in human immune and hematopoietic systems. But can knowledge of a colonial tunicate’s immune system really contribute to our understanding of human immunology, health, and disease? Absolutely! Information discovered in these tunicates (such as the research highlighted by Rosental and colleagues) can deepen our understanding of organ transplantation (to help reduce rejections) and can even aid in uncovering new ways to eliminate cancer cells. Official petition to start a “Tunicate Appreciation Day,” anyone?