Erin L. Davies, Ph.D.
Dr. Davies is investigating the embryonic origin and regulation of adult pluripotent stem cells required for tissue maintenance, whole-body regeneration, and reproduction in planarian flatworms. By studying pluripotency and regeneration as emergent developmental properties, her laboratory will determine how embryonic developmental programs are adapted postnatally for tissue replacement and repair, how these programs may be co-opted to promote cancer initiation or progression.
1) embryogenesis, 2) stem cells, 3) regeneration, 4) reproduction, 5) planaria
Research in the Davies laboratory aims to determine the mechanisms underlying establishment of sustained pluripotency and regeneration competence during planarian embryogenesis. These studies will provide paradigms for manipulating potency and will reveal how embryonic developmental programs are adapted postnatally for tissue maintenance and regeneration.
Dr. Davies is soliciting applications from post-baccalaureate and post-doctoral candidates for full-time, fully funded research positions in the lab. Interested scientists should contact Dr. Davies directly to discuss training opportunities and research projects.
How are adult pluripotent stem cells established during embryogenesis?
Like mammalian epiblast cells, planarian embryonic pluripotent stem cells (PSCs) give rise to all adult tissues. While potency of epiblast descendants diminishes rapidly following uterine implantation, embryonic pluripotency networks remain active in adult PSCs throughout life, fueling tissue homeostasis and regeneration.
We are working to decipher the molecular mechanisms underlying the embryonic to adult pluripotency transition during planarian embryogenesis. As a first step towards this goal, we are defining embryonic and adult PSCs in Schmidtea mediterranea embryos using molecular and functional criteria. My published data strongly indicate that cycling, piwi-1+ embryonic PSCs give rise to adult PSCs as organogenesis begins. Adult PSCs are functionally defined by the ability of a single transplanted cell to rescue a lethally irradiated adult host devoid of stem cells. To determine whether, and when, embryonic piwi-1+ cells begin to function as adult PSCs, we are performing bulk and single cell transplantation using prospectively isolated piwi-1+ donor cells from staged embryos and irradiated adult hosts.
To determine how gene expression signatures for PSC and progenitor populations change during development, we are generating a single cell RNA-Seq atlas using sorted embryonic cells from stages bookending the embryonic to adult pluripotency transition. Differential gene expression among cells from the same stage will identify biomarkers and candidate regulators of pluripotent cell states and progenitors embarking on tissue-specific differentiation programs. Cross-stage comparisons will identify candidate cell-intrinsic regulators of the embryonic to adult pluripotency transition and will reveal changes in the PSC lineage repertoire during embryogenesis. Importantly, this expression resource will facilitate comparison of pluripotent cell populations across species, a first step in determining whether homologous genes and pathways regulate potency in planarians and mammals.
What steps in somatic tissue development are necessary for regeneration competence?
Regeneration emerges through interactions between adult PSCs and surrounding tissues. The Davies lab will determine aspects of somatic tissue development required for niche formation and non-cell autonomous regulation of adult PSC behavior. Through comparison of regeneration-incompetent versus regeneration-competent embryos, we are identifying the tissues, signaling pathways and gene regulatory networks necessary for regeneration. At present, we are testing whether somatic tissue maturation limits establishment of head regeneration ability. These experiments will suggest strategies for reconstituting self-organizing regenerative responses in vitro, and for reverse-engineering regeneration in systems maintained by adult stem cells.
View Dr. Davies' Google Scholar Bibliography.
Selected Recent Publications
- eLife. 10.7554/eLife.21052: 2017. [ Journal Article ]
Sustained pluripotency underlies extreme developmental and reproductive plasticity.In: Deferring Development: Setting Aside Cells for Future Use in Development and Evolution. CRC Press/Taylor & Francis Group 185-196, 2019. [ Journal Article ]
Prospectively isolated Tetraspanin+ neoblasts are adult pluripotent stem cells underlying planaria regeneration.Cell. 173: 1593 -1608, 2018. [ Journal Article ]
Dr. Davies is a developmental biologist with expertise in genetics, stem cells, germ cell and reproductive biology, and tissue regeneration. As a graduate student in Dr. Margaret Fuller’s lab at Stanford University, she studied how non-cell autonomous signals and cell-intrinsic determinants coordinate adult stem cell behavior in the Drosophila testis stem cell niche.
As a postdoctoral researcher with Dr. Alejandro Sánchez Alvarado at the Stowers Institute for Medical Research, Dr. Davies pioneered molecular and functional studies of embryogenesis in the planarian flatworm, Schmidtea mediterranea, a long-lived animal with seemingly unlimited regenerative potential. Unique among well-established research organisms, planarians possess adult pluripotent stem cells required for tissue homeostasis, whole-body regeneration, and reproduction. Planarian stem cells are highly proliferative, yet planarians neither senesce nor develop cancer. As a Stadtman Investigator, Dr. Davies will leverage the understudied context of planarian embryogenesis to determine the mechanisms underlying establishment of sustained pluripotency and regeneration competence. Her lab’s work will broaden our understanding of potency regulation, growth control, tumor suppression, aging, and tissue regeneration.