Important role of PDGF-B discovered in placental niche
By Rachel Ventura
A human’s life in the womb is a strange and unknown yet vital part of the human’s entire life. None of us remember our time in the womb which doesn’t help our understanding. Yet even if we did remember, we wouldn’t have been aware of the molecular processes happening. Fortunately for future foetuses, researchers at the University of California have recently discovered one more thing to assist in our understanding of molecular life in the womb.
To start with, we need to expand our vocabulary.
A placental niche is essentially a niche in the placenta that creates an ideal environment for stem cell expansion and generation but not differentiation. So if a stem cell – or in this case, a blood precursor – differentiates in this placental niche, it is considered premature differentiation (University of California, 2012).
Trophoblasts are the cells on the outermost layer of a blastocyst as seen in Figure 1. The fertilised egg attaches to the uterine wall via these cells (Dorland's Medical Dictionary for Health Consumers, 2007), they later become the placenta and they regularly signal the protein PDGF-B.
Erythropoietin is a hormone that initiates the production of haemoglobin but more importantly, promotes the differentiation of blood precursors to red blood cells (MedicineNet, 2001). If you put all the pieces together, you will come to the conclusion that if this hormone is secreted too early, premature differentiation will occur.
But what did the team at the University of California do? The purpose of the study was to determine which signalling pathways in the placental niche were important for development. Basically they disrupted the placental structure in mice and observed the outcome as a result of this disruption (University of California, 2012). It was already known that the placenta is a place for a significant number of undifferentiated blood cells. What was unknown, however, was the signalling pathway responsible for maintaining the blood cells in their undifferentiated state. It was found that the signalling of PDGF-B in trophoblasts directly correlates to the suppression of EPO (University of California, 2012). Once again, you should have made the connection that if the protein doesn’t get signalled, the hormone will not be suppressed and premature differentiation will occur, resulting in unwanted production of blood cells in the placenta.
The real question is now, what is so important about when red blood cells differentiate, anyway? I mean, they’ve got to differentiate eventually, don’t they? Well, yes but not in the placental niche. As I said before, the placental niche is a place for stem cell expansion and generation only. The time of blood precursor differentiation is essential for ensuring the required blood supply for the foetus’ whole life both in and outside of the womb. Not much more is known about how the premature differentiation affects the foetus however it is suggested that it has a large contribution to developmental defects.
Now that we know the protein responsible for the suppression of the hormone that differentiates these blood precursors, we are closer to understanding and possibly fixing some issues that occur during the developmental stage of the foetus.
Dorland's Medical Dictionary for Health Consumers. (2007). Trophoblast. Retrieved March 14, 2012, from http://medical-dictionary.thefreedictionary.com/Trophoblasts
MedicineNet. (2001). Definition of Erythropoietin (EPO). Retrieved March 14, 2012, from http://www.medterms.com/script/main/art.asp?articlekey=7032
University of California. (2012, March 1). Study reveals crucia cell and signaling pathway that regulate the placental hematopoietic niche. Retrieved March 13, 2012, from https://stemcell.ucla.edu/sites/default/files/MikkolaDevelopmenCellNR.pdf
University of Leeds. (n.d.). Female Reproductive System: Early embryonic development. Retrieved Month 15, 2012, from http://www.histology.leeds.ac.uk/female/embryo.php
Ventura, R. (2012). Flow Chart