Transcriptional networks controlling stromal cell differentiation
Alexander Rauch and Susanne Mandrup highlight recent advances made by in vitro and in vivo studies that expand our current understanding of the differentiation of stromal cells from single factor and pathways to a systems level.
When Alexander Rauch is asked to describe his research to a complete outsider, he uses words such as ‘How can I build new bones? Can you build new fat tissue that is insulin sensitive? Can you control the process so that you can replace old components in the body with new ones that are better than the old ones? In other words, can you become a better version of yourself?’.
When he has to explain his research to fellow scientists, he can start from an article he has just written for Nature Reviews Molecular Cell Biology with Professor Susanne Mandrup, his mentor and former postdoc supervisor: ‘Transcriptional networks controlling stromal cell differentiation’ - an article in which the authors conclude that knowledge now exists that is helping to better understand stromal progenitor biology and its implication in human diseases and the decline of tissue integrity, and to improve clinical therapies aimed at restoring endogenous stromal cell function and cell-based regenerative therapies.
Alexander Rauch is a former DDA postdoc and now Assistant Professor, Institute of Clinical Research, Molecular Endocrinology and Stem Cell Research Unit, Department of Endocrinology at Odense University Hospital.
Giving rise to cells of connective tissues such as bone, fat or cartilage
In the article, he and Susanne Mandrup establish that stromal progenitors, formally known as mesenchymal stem/stromal cells (MSCs), are progenitors that give rise to cells of connective tissues such as bone, fat or cartilage. These progenitors are found in many different tissues, where they play an important role in the maintenance of tissue homeostasis and tissue repair upon injury, owing to their ability to differentiate into parenchymal cells.
‘This differentiation process is characterized by a gradual reduction in expression of genes important for the undifferentiated state and the de novo expression of genes that are characteristic of the function of the differentiated cell, such as collagen deposition and matrix mineralization for osteoblasts and chondrocytes, lipid synthesis and storage for adipocytes, or contractile fibre formation for muscle cells’, says Alexander Rauch. Defects in the differentiation contribute to developmental diseases such as lipodystrophy, muscular dystrophy or osteogenesis imperfecta as well as to ageing-related decline in tissue integrity in patients with osteoporosis, arthritis and sarcopenia.
"Can you build new fat tissue that is insulin sensitive? Can you control the process so that you can replace old components in the body with new ones that are better than the old ones? In other words, can you become a better version of yourself?" |
Clinical outcome highly variable
Due to the ease of isolating, propagating and differentiating stromal progenitors in culture, these cells have gained huge momentum for use in regenerative therapies, as reflected in thousands of ongoing clinical trials. Despite promising outcomes in animal studies and the approval of 10 cell-based therapies, the clinical outcome is highly variable, which emphasizes the importance of improving the molecular understanding of mechanisms regulating stromal cell differentiation.
Alexander Rauch and Susanne Mandrup highlight recent advances made by in vitro and in vivo studies that expand our current understanding of the differentiation of stromal cells from single factor and pathways to a systems level. They discuss the transcriptional networks that drive differentiation into adipocytes, chondrocytes and osteoblasts as well as muscle cells and compare these processes to highlight general principles of cellular differentiation and the ways in which environmental as well as tissue-specific signals shape, interfere with and disrupt commitment during health and disease.
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Read the article here: Nat Rev
Article published: 9 April 2021
Alexander Rauch
Assistant Professor
Institute of Clinical Research
Molecular Endocrinology and Stem Cell Research Unit
Department of Endocrinology
Odense University Hospital
Steno Diabetes Center Odense
Phone: +45 65 50 79 77
arauch@health.sdu.dk
http://www.sdu.dk/ansat/arauch.aspx
University of Southern Denmark
