Strict lineage tracing is crucial for research into nerve cell regeneration, according to one study:

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in vivo converted into functional mouse neurons (red). The image is from a previous study by the Chun-Li Zhang lab at UT Southwestern.” title=”Strict line tracing”/>

Using strict lineage tracing, researchers at UT Southwestern showed that glial cells could be in vivo converted into functional mouse neurons (red). The image is from a previous study by the Chun-Li Zhang lab at UT Southwestern.

DALLAS – September 27, 2021 – Southwestern UT stem cell scientists discover that rigorous lineage tracing is crucial for studies of nerve cell regeneration. Their results, published in Cell, show that this tracing is far from routine in the field and suggest that previous studies reporting “striking” regeneration results need to be re-examined.

Lineage tracing, which is a fundamental approach in developmental biology, refers to the tests used to map the progeny – or progeny – 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 these tests were missed, the authors write in the study recently published in Cell, one of the most reputable scientific journals in the world. The two corresponding authors are Chun-Li Zhang, Ph.D., professor of molecular biology and WW Caruth, Jr. Scholar in biomedical research; and Lei-Lei Wang, Ph.D., molecular biology instructor and member of the Zhang lab, who studies nerve cell regeneration in the brain and spinal cord.

Drs.  Carolina Serrano Garcia, Chun-Li Zhang and Lei-Lei Wang

Drs. Carolina Serrano Garcia, Chun-Li Zhang and Lei-Lei Wang

“From the start, we have used the strictest methods to analyze the regeneration of nerve cells. So it was amazing to read a number of other articles – including some that make phenomenal claims – that did not do careful analysis, ”said Dr Zhang, member of the Hamon Center for Regenerative Science and Medicine. at UT Southwestern.

After conducting dozens of experiments using a range of protocols, the researchers identified the specific lineage-tracing tests that appeared to be the most robust and reliable – the so-called benchmark tests. “We used the line tracing tests currently available. No new has been developed, ”said Dr Zhang. Scientists have also identified tests that are less likely to provide accurate results.

The study concludes by listing reliable traceability tests and strongly recommending that these tests be used in all laboratories researching nerve cell regeneration. “The methods we list are easy to set up in a lab and we believe they should always be used,” he said.

Dr Zhang obtained his doctorate. in Genetics and Development from UT Southwestern Medical Center, where he worked on muscle development and heart disease. He conducted postdoctoral research on neural stem cells as a fellow of the Howard Hughes Medical Institute of the Life Sciences Research Foundation at the Salk Institute in La Jolla, California.

At UT Southwestern, Dr. Zhang’s lab reported several advances in neural stem cell biology, such as brain and spinal cord regeneration in mice after injury. The scientist recognized his lab’s work on reprogramming cell fate in living animals as one of the great scientific breakthroughs of 2014. He won the prestigious New Innovator Award from the National Institutes of Health Director in 2009.

Using rigorous lineage tracing, the team at Drs. Wang and Zhang reported in 2018 that while trying to turn 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 the disease. of Parkinson’s. Their study found that neurons in the brain were more malleable in adulthood than previously thought.

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

UTSW co-authors are: Carolina Serrano Garcia, Xiaoling Zhong, Shuaipeng Ma and Yuhua Zou.

The Welch Foundation supported the study (I-1724), as did the Decherd Foundation, the Kent Waldrep Foundation Center for Basic Research on Nerve Growth and Regeneration, the Texas Alzheimer’s Research and Care Consortium (TARCC2020) and the NIH (NS099073, NS092616, NS111776, NS117065 and NS088095).

The authors declare no competing interests.

About UT Southwestern Medical Center

UT Southwestern, one of the nation’s leading academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has been awarded six Nobel Prizes and includes 25 members of the National Academy of Sciences, 16 members of the National Academy of Medicine and 14 researchers of the Howard Hughes Medical Institute. The full-time faculty of over 2,800 is responsible for revolutionary medical advancements and is committed to rapidly translating science-driven research into new clinical treatments. Doctors at UT Southwestern provide care in approximately 80 specialties to more than 117,000 inpatients, more than 360,000 emergency room cases and supervise nearly 3 million outpatient visits per year.




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