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Strict lineage tracing crucial to nerve cell regeneration research, study says

DALLAS, TX (US), October 2021 – University of Texas Southwestern stem cell scientists find that stringent lineage tracing is crucial for studies of nerve cell regeneration. Their results 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. The two corresponding authors are Chun-Li Zhang, Ph.D., a professor of molecular biology, and Lei-Lei Wang, Ph.D., an instructor of molecular biology and member of the Zhang lab, which studies nerve cell regeneration in the brain and spinal cord.

“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 Dr. Zhang.

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,” Dr. Zhang 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.

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DOI: 10.1016/j.cell.2021.09.005