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Cell Stem Cell

Gene silencing lasts and partly reverses in human blood stem cells

Silencing of a platelet-related gene remained stable four months after human stem cells were transplanted into mice.

Paper by Tianyi Ye, Wanying Xu, Maria N. Barrachina, +18 more authorsVijay G. Sankaran
Graphical abstract from Cell Stem Cell
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Graphical abstract. Ye et al., CC BY

Our read

Interventions
Studied:
Experiments in primary human hematopoietic stem cells, 4 months
What changed:
ITGB3 silencing persisted for 4 months after transplantation and partly reversed with targeted demethylation
The catch:
Silencing stability after transplantation was followed for only 4 months
Why it’s aging research:
It studies how the body can be repaired or renewed.

Editor of record: Boris Djordjevic · AgingResearch.News

Paper
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Primary human hematopoietic stem cells, which give rise to blood cells, received RNA-delivered tools for controlling gene activity in a laboratory experiment. These tools used DNA methylation—chemical marks on DNA—to silence genes without changing the DNA sequence.

Targeting ITGB3, a gene for a platelet surface protein, produced silencing that persisted as the stem cells renewed themselves and developed into platelet-producing cells. Platelets made in the lab showed reduced aggregation, or clumping together. Targeted removal of DNA methylation partly reversed the silencing. Silencing also remained stable in human stem cells four months after transplantation into mice. Targeting other platelet-associated genes showed that the approach could work beyond ITGB3.

Why it matters

Stem-cell renewal is one process studied in aging biology. The platform offers a way to explore lasting but adjustable changes in the function of blood cells produced by these stem cells.

Caveats

The platelet-function result came from platelets made in the lab. Stability after transplantation was tested in mice, not in people.

Where the evidence stands

DNA methylation

Cells, mice and humans: replicated by independent labs. Worms or flies: a single group.

C, W, M, H: cells, worms or flies, mice, humans. Dark: independent labs found the same change there. Light: one lab or one study. Outline: nothing yet.

Labs are independent when their papers share no last author and no institution.

Against: findings that point the other way from most findings on the same outcome.

Company ties: findings with an author at a company, or from a paper whose competing-interests statement declares ties to one.

Includes the processes named after it and trials of drugs aimed at it.

  • 196 independent labs in 38 countries
  • 18 findings against
  • Funders: National Institutes of Health and others
  • 42 of 393 findings with company ties

ITGB3

Cells: replicated by independent labs. Mice: a single group. Worms or flies and humans: nothing yet.

C, W, M, H: cells, worms or flies, mice, humans. Dark: independent labs found the same change there. Light: one lab or one study. Outline: nothing yet.

Labs are independent when their papers share no last author and no institution.

Company ties: findings with an author at a company, or from a paper whose competing-interests statement declares ties to one.

Includes the processes named after it and trials of drugs aimed at it.

  • 13 independent labs in 4 countries
  • 1 trial
  • Funders: National Institutes of Health and others
  • 1 of 20 findings with company ties
  • 1 of 1 trial sponsored by developers of drugs aimed at it

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