This glycolytic shift represents an early reprogramming event, preceding the expression of genes controlling pluripotency and self-renewal. Thus, metabolic transformation might control cell fate identity. Modulation of bioenergetics is particular important for the development of the nervous systems, which consumes almost half of the whole-organism basal metabolic rate. However, the regulatory role of mitochondria and energy metabolism in dictating neural commitment and orchestrating its epigenetic rewiring remains to be investigated.
In this project, we seek to dissect the potentially instructive role of bioenergetic restructuring for cell fate conversion and neural specification in particular. We will first focus on defined cellular states (fibroblasts, iPSCs, neural progenitors, neurons, and astrocytes) to map their mitochondrial/metabolic signature and the downstream effects on the epigenetic landscape. We will then analyze the mechanistic function of mitochondria and energy metabolism during reprogramming to iPSCs and upon glial and neuronal differentiation, by altering nutrient availability and by chemical and genetic manipulation of critical mitochondrial and metabolic regulators. Finally, we wish to integrate the obtained data to computationally build a metabolic map of cell identities. This will be coupled to mitochondrial-related high throughput assays to possibly identify enablers of metabolic-driven cellular conversions. Overall, these studies may lead to a better understanding of the importance of mitochondria and metabolism for brain development and for the control of cell fate plasticity and specification.
Mlody B, Prigione A.
Cell Stem Cell. 2016 Oct;19(4):419-420. doi: 10.1016/j.stem.2016.09.005.
Prigione A, Rohwer N, Hoffmann S, Mlody B, Drews K, Bukowiecki R, Blümlein K, Wanker EE, Ralser M, Cramer T, Adjaye J.
Stem Cells. 2014 Feb;32(2):364-76. doi: 10.1002/stem.1552.
Bukowiecki R, Adjaye J, Prigione A.
Gerontology. 2014;60(2):174-82. doi: 10.1159/000355050. Epub 2013 Nov 19. Review.
Prigione A, Lichtner B, Kuhl H, Struys EA, Wamelink M, Lehrach H, Ralser M, Timmermann B, Adjaye J.
Stem Cells. 2011 Sep;29(9):1338-48. doi: 10.1002/stem.683.
Prigione A, Adjaye J.
Int J Dev Biol. 2010;54(11-12):1729-41. doi: 10.1387/ijdb.103198ap.
Prigione A, Fauler B, Lurz R, Lehrach H, Adjaye J.
Stem Cells. 2010 Apr;28(4):721-33. doi: 10.1002/stem.404.
- PMID: 20201066