The stem cell scientists find that stringent lineage tracing is crucial for studies of nerve cell regeneration. Their results, which are published in Cell, show that this tracing is far from routine in the field and suggest that earlier studies reporting “striking” regeneration results must be reexamined.

Lineage tracing, which is a fundamental approach in developmental biology, refers to tests used to map out the progeny – or descendants – of a given cell in an organism.

Lineage tracing is also central to the field of stem cell biology, so it was surprising to learn how often such testing had been omitted, the authors write in the newly published study in Cell, one of the world’s most highly regarded scientific journals.

“We have from the start employed the most stringent methods to analyze nerve cell regeneration. It was therefore astonishing to read a number of other papers – including some that make phenomenal claims – that failed to do careful analyses,” said one of the corresponding authors.

After running dozens of experiments using a range of protocols, the researchers identified which specific lineage tracing assays appeared most robust and reliable – the so-called gold standard tests. “We employed the currently available lineage tracing assays. No new ones were developed,” the author said. The scientists also identified tests that were less likely to provide precise results.

The study concludes by listing reliable lineage tracing tests and strongly recommending these assays be used in all laboratories doing nerve cell regeneration research. “The methods we list are straightforward to establish in a laboratory, and we believe they should always be used,” the author said.

Using rigorous lineage tracing, the team reported in 2018 that while attempting to transform a type of brain cell known as a glial cell into a neuron, they instead reprogrammed mature inhibitory neurons into a different type of neuron that produces the neurotransmitter lost in Parkinson’s disease. Their study indicated that the brain’s neurons were more malleable in adulthood than previously thought. 

Earlier this year, they reported in Cell Stem Cell that the latent neurogenic potential of glial cells can be leveraged to produce new neurons and lead to functional recovery after spinal cord injury in mice.

https://www.utsouthwestern.edu/newsroom/articles/year-2021/strict-lineage-tracing.html

https://www.cell.com/cell/fulltext/S0092-8674(21)01052-7