Pollen lab and Kriegstein lab publish cover article describing the potential to compare human and ape brain development using stem cell derived organoid models

Chimpanzee ‘mini-brains’ hint at secrets of human evolution

February 8, 2019

By Nicholas Weiler | UCSF

At some point during human evolution, a handful of genetic changes triggered a dramatic threefold expansion of the brain’s neocortex, the wrinkly outermost layer of brain tissue responsible for everything from language to self-awareness to abstract thought. Identifying what drove this evolutionary shift is fundamental to understanding what makes us human, but has been particularly challenging for scientists because of ethical prohibitions against studying the developing brains of our closest living relative, the chimpanzee, in the lab.

“By birth, the human cortex is already twice as large as in the chimpanzee, so we need to go back much earlier into embryonic development to understand the events that drive this incredible growth,” said Arnold Kriegstein, MD, Ph.D., the John Bowes Distinguished Professor in Stem Cell and Tissue Biology, founding director of the Eli and Edyth Broad Center of Regenerative Medicine and Stem Cell Research at UC San Francisco, and member of the UCSF Weill Institute for Neurosciences.

In a study published February 7, 2019, in Cell, Kriegstein and collaborators have gotten around this impasse by creating chimpanzee brain “organoids”—small clusters of brain cells grown from stem cells in a laboratory dish that mimic the development and organization of full-size brains.

Kriegstein’s group was among the early pioneers of growing human brain organoids from so-called induced pluripotent stem cells (iPSCs)—adult cells (usually skin cells) reprogrammed into stem cells that can become any tissue in the body. Organoids have since become a valuable tool for studying human tissue development and disease in a controlled laboratory setting, but the new study, in which the researchers generated 56 organoids from stem cells derived from the skin of eight chimpanzees and 10 humans, marks the first time researchers have been able to produce and study chimpanzee brain organoids en masse.

“Our ability to take skin cells from an adult chimpanzee, turn them into iPSCs, and then study their development in laboratory dishes is astounding,” said Kriegstein. “It’s a ‘science fiction’ experiment that couldn’t have happened 10 years ago.”

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