Many tissues including the brain contain quiescent stem cell populations, which are activated upon damage. We study recently discovered damage-responsive neural stem cells in the fruit fly, which start proliferating after traumatic brain injury and efficiently produce new neurons in the injured brain region. We want to uncover the injury signals and molecular mechanisms that activate neural stem cells and control regenerative neurogenesis. We are also interested in understanding how altered stem cell plasticity (hyperactivation or adult neural stem cell loss) impacts on tissue regeneration, aging and cancer.
To uncover regulators of stem cell activation and neural differentiation, we use highly sensitive lineage tracing tools, in combination with whole genome expression profiling, functional genetics and high-end confocal microscopy.
Moreover, we complement current efforts to understand brain regeneration at the cellular level with behavioral assays to answer fundamental questions such as how adult-born neurons integrate into pre-existing circuits and how they may contribute to recovery of impaired brain functions after injury. This setup allows us to interrogate brain restorative processes in a holistic fashion.

Overview

We are interested in understanding the molecular mechanisms that drive and stop the activation, proliferation and differentiation of quiescent stem cells with implications for tissue homeostasis, cancer and regeneration.

Stem cell control

Many mammalian tissues contain pools of quiescent adult stem cells, which are only activated in pathological conditions or upon injury and have been proposed to act as a backup population. Regulation of stem cell quiescence and the intrinsic mechanisms by which cells sense and respond to injury-related signals are not well understood.
To unravel such mechanisms, we study recently discovered quiescent adult neural stem cell in the genetically accessible model organism Drosophila, which are activated upon traumatic brain injury by stab lesion (Fernandez-Hernandez et al., 2013)
To reach this goal, we perform whole genome expression profiling (microarrays and RNAseq) in combination with powerful functional RNAi assays and expression studies to validate candidate genes, followed by detailed characterization of conserved components.

Regenerative neurogenesis and function

We also seek to answer fundamental questions such as how adult-born neurons integrate into the mature brain and if their integration contributes to recovery of brain function after injury. To this end, we apply high-end microscopy, electrophysiology and behavioral assays to monitor performance after injury.

Christa Rhiner, PhD
Principal Investigator
christa.rhiner@research.fchampalimaud.org

Biography

Carolina Alves
Research Technician
carolina.alves@research.fchampalimaud.org

Margarida Caio
PhD Student
margarida.caio@research.fchampalimaud.org

Marta Neto, PhD
Postdoctoral Researcher
marta.neto@research.fchampalimaud.org

Lab Administration

Vesna Petojevic
Lab Administrator
vesna.petojevic@neuro.fchampalimaud.org

PhD Student

Anabel Rodriguez Simões
PhD Student
anabel.rodriguez@neuro.fchampalimaud.org

Bosch PS, Makhijani K, Herboso L, Gold KS, Baginsky R, Alexander B, Woodcock KJ, Kukar K, Corcoran S, Ouyang D, Wong C, Ramond EJV, Rhiner C, Moreno E, Lemaitre B, Geissmann F and Brückner K. Adult Drosophila lack signs of hematopoiesis, but are a model (2020) Adult Drosophila lack signs of hematopoiesis, but are a model for organismal immunity centered at the blood cell reservoir of the respiratory epithelia Nature

Dina S. Coelho, Silvia Schwartz, Marisa M. Merino, Barbara Hauert, Barbara Topfel, Christa Rhiner and Eduardo Moreno (2018) Culling less fit neurons protects against amyloid-Beta-induced brain damage and cognitive and motor decline Cell Rep (doi:10.1016/j.celrep.2018.11.098)

Schwartz S and Rhiner C (2018) Reservoirs for Repair? Damage-responsive stem cells and adult tissue regeneration in Drosophila Int. J. Dev. Biol.

Simões AR, Rhiner C (2017) A Cold-Blooded View on Adult Neurogenesis Front Neurosci (doi:10.3389/fnins.2017.00327)

Moreno E., Fernandez-Marrero, Y., Meyer, P., and Rhiner, C (2015) Brain regeneration in Drosophila involves comparison of neuronal fitness Curr. Biol. (doi:10.1016/j.cub.2015.02.014)

Merino MM, Rhiner C, Lopez-Gay JM, Buechel D, Hauert B, Moreno E (2015) Elimination of unfit cells maintains tissue health and prolongs lifespan Cell (doi:10.1016/j.cell.2014.12.017)

Moreno E, Fernandez-Marrero Y, Meyer P, Rhiner C. (2015) Brain regeneration in Drosophila involves comparison of neuronal fitness. Curr. Biol. (doi:doi: 10.1016/j.cub.2015.02.014)

Moreno, E. and Rhiner, C (2014) Darwin`s multicellularity: From neurotrophic theories and cell competition to fitness fingerprints Curr Op Cell Bio (doi:10.1016/j.ceb.2014.06.011)

Merino MM, Rhiner C, Portela M, Moreno E (2013) "Fitness fingerprints" mediate physiological culling of unwanted neurons in Drosophila Curr. Biol. (doi:10.1016/j.cub.2013.05.053)

Rhiner C, López-Gay JM, Soldini D, Casas-Tinto S, Martín FA, Lombardía L, Moreno E (2010) Flower Forms an Extracellular Code that Reveals the Fitness of a Cell to its Neighbors in Drosophila Dev. Cell

Portela M, Casas-Tinto S, Rhiner C, López-Gay JM, Domínguez O, Soldini D, Moreno E (2010) Drosophila SPARC is a self-protective signal expressed by loser cells during cell competition Dev. Cell