Mitochondrial dynamics in postmitotic cells regulate neurogenesis
Authors: Pierre Vanderhaeghen
Ryohei Iwata
Pierre Casimir
Journal: Science (2020)
Discipline: Multidisciplinary
Keywords: neural stem cells; neurons; organelles; fate change; mitochondrial dynamics
Affiliations: VIB Center for Brain and Disease Research, 3000 Leuven, Belgium., Department of Neurosciences, Katholieke Universiteit (KU) Leuven, 3000 Leuven, Belgium., Leuven Brain Institute, KU Leuven, 3000 Leuven, Belgium., Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium., ULB Neuroscience Institute (UNI), ULB, 1070 Brussels, Belgium., VIB Center for Brain and Disease Research, 3000 Leuven, Belgium. .

Abstract:  The conversion of neural stem cells into neurons is associated with the remodeling of organelles, but whether and how this is causally linked to fate change is poorly understood. We examined and manipulated mitochondrial dynamics during mouse and human cortical neurogenesis. We reveal that shortly after cortical stem cells have divided, daughter cells destined to self-renew undergo mitochondrial fusion, whereas those that retain high levels of mitochondria fission become neurons. Increased mitochondria fission promotes neuronal fate, whereas induction of mitochondria fusion after mitosis redirects daughter cells toward self-renewal. This occurs during a restricted time window that is doubled in human cells, in line with their increased self-renewal capacity. Our data reveal a postmitotic period of fate plasticity in which mitochondrial dynamics are linked with cell fate. 

Retracted: No

PubPeer comments:
 Readers should be aware that some of the statistical analyses in this article may suffer from pseudoreplication. Examples are found in Fig. 1E and 1G, which plot the lengths of mitochondria per cell. There are tens of cells drawn from  three biological replicate experiments . The groups appear to be different and are worth four stars of significant difference (p 0.0001). But how many degrees of freedom did the authors use in their test? I can t find that information, but I m going to guess that means they used tens and not the number of biological replicates. (This seems to be a very common loophole in journal instructions: to require the number of replicates without ever mandating their use in the statistical tests.) Maybe the  reproducibility checklist can help? Well, according to that biological replicates are  n a (despite being mentioned in the legends), so oops for the reproducibility procedures at Science. Maybe we can deduce what happened from the data and analysis code? No analysis code seems to be available. Oh well, lets just try to reconstitute a sensible analysis from the data ourselves. Fortunately, the paper says this:  Data and materials availability: All data are available in the manuscript or the supplementary materials . Unfortunately, I can t find it. Apologies if I missed it. Now I m wondering whether the authors have a different definition of  data to mine. This is of course sadly normal, even (particularly?) in glamour journals: tiny sample sizes, incomplete statistical description, probably invalid test, incorrect checklist, incorrect data availability statement, data unavailable, no analysis code. Note that these issues may not change the conclusions (if you are inclined to believe n = 3 experiments). Nevertheless, these gain-of-function experiments are absolutely key to the paper. This is because loss-of-function experiments have little value for studies of organelles as essential as the mitochondria. ,