Using organoids to find out what sets apart the human brainGroup Leader Page
The human brain is greatly expanded compared to that of other apes. The molecular mechanisms underlying this unique anatomy, which is at the root of our advanced cognition, are still unknown. This is largely due to a lack of appropriate model systems to accurately recapitulate the human developing brain, until now. With the recent development of 3D neural tissues in a dish, called brain organoids, it is now possible to study development of human brain tissue and compare it with our closest living relatives. In the Lancaster lab we have done just that, and very recent findings have identified a key developmental transition that takes longer in humans compared with other apes. The result of this protracted transition is an increased number of founder stem cells that set up the blueprint of the cerebral cortex, leading to its enlargement. However, while we have a solid understanding of the cell biological mechanisms, we still lack a molecular understanding, namely, what are the genetic changes responsible for this human-specific increase in neural stem cells? This project will aim to answer this question through a combination of comparative genomics, transcriptomics, and epigenomics in brain organoids of various primate species. The project will include state-of-the-art techniques, in a collaborative and fun atmosphere, with excellent resources and support, to seek to answer one of the oldest questions in human biology: what makes us human?
Benito-Kwiecinski S, Giandomenico SL, Sutcliffe M, Riis ES, Freire-Pritchett P, Kelava I, Wunderlich S, Martin U, Wray G, McDole K, Lancaster MA. (2021)
An early cell shape transition drives evolutionary expansion of human forebrain.
Kelava I, Chiaradia I, Pellegrini L, Kalinka AT, Lancaster MA. (2022)
Androgens increase excitatory neurogenic potential in human brain organoids.
Nature. 602(7895), 112-116.
Chiaradia I, Lancaster MA. (2020)
Brain organoids for the study of human neurobiology at the interface of in vitro and in vivo.
Nat Neurosci. (12):1496-1508.
Pellegrini L, Bonfio C, Chadwick J, Begum F, Skehel M, Lancaster MA. (2020)
Human CNS barrier-forming organoids with cerebrospinal fluid production.
Giandomenico SL, Mierau SB, Gibbons GM, Wenger LMD, Masullo L, Sit T, Sutcliffe M, Boulanger J, Tripodi M, Derivery E, Paulsen O, Lakatos A, Lancaster MA. (2019)
Cerebral organoids at the air-liquid interface generate diverse nerve tracts with functional output.
Nat Neurosci. (4):669-679.
Lancaster MA, Renner M, Martin C-A, Wenzel D, Bicknell LS, Hurles ME, Homfray T, Penninger JM, Jackson AP, Knoblich JA. (2013)
Cerebral organoids model human brain development and microcephaly.