I’m interning in the Department of Totipotency at the Max Planck Institute of Biochemistry - here’s an introduction to what stem cells and totipotency are!
Types of stem cells
You might remember from biology in school that stem cells are undifferentiated or unspecialised cells, which can divide and differentiate to produce the specialised cells of the body, like neurons, red blood cells, and muscle cells, among many others. There are over 200 different types of specialised cells in the human body! In the news, you might have seen ethical issues regarding embryonic stem cells, or stem cells as therapies to cure disease. There are several different types of stem cells: the main classes (from least to most undifferentiated) are multipotent, pluripotent, and totipotent. All stem cells have 2 key properties: the ability to self-renew (divide and replace themselves), and the ability to differentiate into different types of specialised cells (i.e. potency). This self-renewal capacity of stem cells is important because it gives us a continuous supply of stem cells which we can use to grow, replace, and repair our tissues.
Multipotent stem cells can only differentiate into a select few different cell types, e.g. haematopoietic stem cells which make all the different blood cells; neural stem cells which generate the neurones and glia; and mesenchymal stem cells which give rise to our bone, cartilage, fat, and muscle cells. These are the stem cells present in adults, e.g. in the bone marrow. Pluripotent stem cells can differentiate to generate all of the body's cell types and make up the inner cell mass of the blastocyst. The blastocyst is a ball of cells formed in early mammalian embryonic development, and this inner cell mass will form the embryo.
Totipotent cells are only found very early on in development, and they are special because they have the potential to differentiate into all of the embryonic cell types (like pluripotent stem cells) as well as the extraembryonic cell types (unlike pluripotent stem cells), which includes the placenta and amniotic membrane. This means that a totipotent cell can divide and differentiate to produce an entire viable organism. When a sperm and egg cell fuse during fertilisation, a zygote is formed - a single-cell embryo. This is a totipotent cell which undergoes division, to form 2, then 4, then 8 cells, and up until the 8 cell stage, all of these cells are totipotent. As they divide further (to eventually form the blastocyst), they will become pluripotent, or form extraembryonic structures.
My lab’s research
I’m interning at Kikuë Tachibana’s lab which researches totipotency, and they are finding factors which reprogram the genetic information from being part of very specialised cells (i.e. sperm and egg) to being part of a totipotent cell, which can differentiate into any cell type. These factors reprogram the chromatin, which is the term for the DNA and the histones associated with it (i.e. the proteins which DNA is wrapped around and can be modified to encode extra information) in the nucleus. One type of factor which could be responsible for this reprogramming is pioneer transcription factors. Transcription factors are proteins which bind to DNA and lead to the expression of specific genes, which affect what a cell will become, e.g. only red blood cells express the genes for haemoglobin, which is the protein that binds oxygen and carries it around the body. However, sometimes transcription factors can’t bind because the DNA is tightly wrapped around histones. Pioneer transcription factors can bind to DNA in this highly compacted state, and open it up, allowing other transcription factors to come in and bind the DNA, leading to a change in gene expression.
In 2012 Shinya Yamanaka was a recipient of the Nobel Prize for Physiology or Medicine discovering that adult differentiated cells can be converted to pluripotent stem cells (known as induced pluripotent stem cells, or iPSCs.), and the factors required to do this are called Yamanaka factors. iPSCs have huge potential in the fields of regenerative medicine because we can take a sample of blood or skin cells from a patient, turn them into iPSCs, grow these cells, and then expose them to different factors which cause them to differentiate into specific cell types, and then study how they act when exposed to different conditions or drugs. This has been done using cells from amyotrophic lateral sclerosis (ALS) patients, which is a motor neuron disease, and scientists generated iPSCs from patient samples, and then differentiated them into different cells including motor neurons (Richard and Maragakis, 2015), which has the potential for us to gain insight into the disease mechanism and do drug screens, identifying medicines which can then go to clinical trials. If we can discover the equivalent factors for totipotency, this would be a groundbreaking contribution to the field.
If you’d like to learn more about stem cells, there are some great resources on the “Explorer’s Guide to Biology” website under the “Cell Biology” collection tab!