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The Cutting Edge

From a Single Blood Stem Cell, Millions of Diverse T Cells

T cells (outlined in green)

A section of an artificial thymic organoid showing T cells (outlined in green) created from blood stem cells.Image: UCLA Broad Stem Cell Research Center/Cell Reports

UCLA scientists have managed to generate a large number of T cells of different subtypes and with different functions from just a single blood cell using a novel approach: lab-grown mouse thymus organoids. Their research furthers the understanding of how T cells arise, which is critical to their potential use in future therapies for certain diseases.

“You need T cells to be able to respond to vaccines, to fight viruses and to control cancerous changes in the body, so there’s a lot of interest in understanding how T cells are made,” says Gay Crooks, MBBS, co-director of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research and Rebecca Smith Professor of Pathology and Laboratory Medicine. “This is a great system to help us study that basic biology.”

All T cells are formed from blood stem cells in the thymus. However, research into how blood stem cells differentiate into T cells has been stymied, because the cells rely on complex chemical signals from the thymus, a process that cannot be replicated easily in a lab dish or in isolated stem cells. After successfully creating lab-grown human thymus organoids — clusters of cells that mimic the thymus — in 2017, Dr. Crooks and her team adapted their work to also make mouse thymus organoids in the lab. This allows a different set of observations on T-cell formation than previously possible, since some types of experiments are possible in mice but not humans. “The main novelty with this mouse system is that we could start with one single stem cell,” says Amélie Montel-Hagen, PhD, associate project scientist in Dr. Crooks’ lab. “It’s amazing that from just one cell you can generate millions of diverse T cells.”

The researchers, who include UCLA MD/PhD candidate Victoria Sun, envision future experiments in which researchers remove or change genes thought to be important for generating T cells and use the thymus organoid to study the effect on mature T cells. While such experiments currently are possible inside genetically engineered mice, following the precise developmental paths of distinct groups of T cells is easier in an isolated laboratory system than in a living animal.

“For us to be healthy, the exquisite balance of immune cells and molecules in our bodies has to be just right,” says Dr. Crooks, who also is director of the Cancer and Stem Cell Biology Program at the UCLA Jonsson Comprehensive Cancer Center. “This will let us study how that balance is regulated.”

— Tiare Dunlap

“In Vitro Recapitulation of Murine Thymopoiesis from Single Hematopoietic Stem Cells,” Cell Reports, October 27, 2020


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IN THIS ISSUE
  • The Year that Was
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  • A Pioneer, a President and a Legacy
  • Team Player
  • Awards and Honors
  • A Special Connection Leads to $29 Million Gift to Advance Genomic Medicine
  • Medical Student Commits to Increasing Opportunities for Minority Students
  • Max Gray Salon Offers Timely Mental Health Tips
  • New Endowed Chair Advances Pediatric Orthopaedics
  • Changing the Paradigm for the Treatment of Sports Concussion
  • Gifts
  • From Russia, with Love
  • The Long Haul
  • How COVID-19 Punished Latinos for Their Hard Work
  • The Natural
  • From a Single Blood Stem Cell, Millions of Diverse T Cells
  • Brain Organoids Grown in Lab Mature on Human Timelines
  • A Method to More Efficiently Isolate and Identify Rare T Cells
  • More Women Embrace “Going Flat” after Mastectomy
  • Brick By Brick
  • Do We Really Want to Return to Normal?
  • Safe Harbor
  • High Percentage of California Youth Struggle with Mental Health Issues
  • Mother and Daughter Send Health Care Workers Virtual Hugs
  • UCLA Donors Join Together to Honor Esteemed Orthopaedic Surgeon
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