In this episode of the Epigenetics Podcast, we caught up with Margaret (“Peggy”) Goodell from Baylor College of Medicine in Houston, Texas to talk about her work on the epigenetic regulation of stem cell self-renewal and differentiation.

Dr. Margret Goodell's laboratory focuses on how differentiation and self-renewal is regulated in hematopoietic stem cells (HSC). In the early stages of her research career, however, Dr. Goodell was able to develop a new method to purify stem cells. This method was based on the characteristic of stem cells to pump out the Hoechst dye that was used for the purification.

In recent years, the focus of the lab has been to identify how HSCs decide whether to self-renew or differentiate. To get an answer to this question, the lab has performed genome-wide screens to find differentially expressed genes during the decision process. By doing that, they recently found that the DNA methyltransferase 3A (DNMT3A) was highly and specifically expressed in HSCs and that it is required for differentiation. When DNMT3A was knocked out in HSCs, the cell population expanded dramatically and the ability to differentiate was impaired. This finding led to further experiments in this area and to the discovery of so-called DNA methylation canyons in the genome, which are large regions of very low DNA methylation that harbor highly conserved regulator genes.

In this episode we discuss how Dr. Peggy Goodell described a new approach to isolate hematopoietic stem cells even though she was not looking for that, how she discovered DNMT3A as an important factor in stem cell decision making, and how she entered and approached new fields of research along the path of her research career. 

 

References

  • M. A. Goodell, K. Brose, … R. C. Mulligan (1996) Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo (The Journal of Experimental Medicine) DOI: 10.1084/jem.183.4.1797
  • Shannon McKinney-Freeman, Margaret A. Goodell (2004) Circulating hematopoietic stem cells do not efficiently home to bone marrow during homeostasis (Experimental Hematology) DOI: 10.1016/j.exphem.2004.06.010
  • Stuart M. Chambers, Chad A. Shaw, … Margaret A. Goodell (2007) Aging hematopoietic stem cells decline in function and exhibit epigenetic dysregulation (PLoS biology) DOI: 10.1371/journal.pbio.0050201
  • Grant A. Challen, Deqiang Sun, … Margaret A. Goodell (2011) Dnmt3a is essential for hematopoietic stem cell differentiation (Nature Genetics) DOI: 10.1038/ng.1009

 

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