Proliferation and Fate Regulation of Stem Cells

Stem cells are required for the embryonic development, growth and regeneration of tissues and organs. 

Stem cells must generate the right type and number of specialized cells to ensure proper tissue and organ formation. Once stem cells have generated their complete set of daughter cells they must disappear.

Stem cells must then be tightly regulated, and if defective this can lead to developmental defects or even to the formation of malignant tumors.

Our group uses the fruit fly Drosophila melanogaster as a model to study the mechanisms that regulate stem cell proliferation and fate during development. We are mainly focused in how temporal and metabolic cues regulate the proliferation and fate of neural stem cells and their daughter cells and consequently brain and animal development.

The understanding of how stem cells are temporally and metabolically regulated is crucial for the understanding of many developmental diseases, tumors and for their use in regenerative medicine.

LOGO_ERC-FLAG_EU__catarina.homem@fcm.u

StemCellHabitat - ERC Starting Grant

Summary:
Stem cells are undifferentiated cells capable of dividing several times to self-renew and to generate more specialized cells essential for tissue, organ and ultimately whole organism formation. Stem cells exist not only in embryos but also in adults, where they are involved in tissue homeostasis and repair. Stem cells harbor a great potential for regenerative medicine since they are potentially great sources of new specialized cells. Although several aspects of stem cell biology are understood it is still not fully known how stem cells are directed to generate specific differentiated cells or how to efficiently regulate stem cell proliferation. Stem cells normally undergo waves of proliferation and quiescence and change the type of differentiated cells they generate throughout animal development. This project aims at studying how stem cells are normally regulated during animal development according to their spatial, temporal and metabolic identity to determine their proliferation and the type of differentiated cells formed. To answer these questions, this project uses Drosophila melanogaster, an animal complex enough to be similar to higher eukaryotes and yet simple enough to dissect the mechanistic details of cell regulation and its impact on the organism. Drosophila has several stem cell populations all dynamically regulated during development and is thus a fantastic model to study stem cells. Using a multidisciplinary approach combining genetics, cell type/age sorting, multi-omics analysis, fixed and 3D-live stem cell imaging and metabolite dynamics, this project proposes an integrative approach to investigate how stem cells are regulated in the developing animal.

This website is part of a project that has received funding from the European Research Council (ERC) under the Horizon 2020 research and innovation programme (Grant agreement No. 759853).

  • 2017 (start date 2018): Metabolic and Timed control of stem cell fate in the developing animal. ERC Starting Grant (European Research Council). 5-year award.
  • 2017: HHMI and Wellcome Trust International Scholar (Howard Hughes Medical Institute). 5-year award.
  • 2016: EMBO Installation Grant. 5-year award.
  • 2015: Starting FCT Investigator Grant and Exploratory project. 5-year award (Fundação para a Ciência e Tecnologia, Portugal.)

Oliveira AC, Rebelo AR, Homem CC (2021) Integrating animal development: How hormones and metabolism regulate developmental transitions and brain formation. Dev Biol 4;S0012-1606(21)00029-4. DOI: 10.1016/j.ydbio.2021.01.016

Garcez M, Branco-Santos J, Gracio PC, Homem CC (2021) Mitochondrial Dynamics in the Drosophila Ovary Regulates Germ Stem Cell Number, Cell Fate, and Female Fertility. Front Cell Dev Biol 28;8:596819. DOI: 10.3389/fcell.2020.596819

Rebelo AR, Garcez M, Homem CC (2020) Tumor start-up: mitochondrial fusion makes it happen. EMBO J 1;39(23):e106927. DOI: 10.15252/embj.2020106927

Homem CC, Repic M, Knoblich JA (2015) Proliferation control in neural stem and progenitor cells. Nat Rev Neurosci. 16, 647-59. DOI: 10.1038/nrn4021

Homem CC, Steinmann V, Burkard TR, Jais A, Esterbauer H, Knoblich JA (2014) Changes in energy metabolism triggered by Ecdysone and Mediator end proliferation in Drosophila neural stem cells. Cell 158, 874-888. DOI: 10.1016/j.cell.2014.06.024

  • 2021 - INPHINIT LaCaixa PhD fellowship (Patricia Grácio)
  • 2020 - FCT PhD fellowship (Ana Rita Rebelo)
  • 2019 - FCT Postdoctoral fellowship (Tiago Baptista)
  • 2019 - EMBO long term Postdoctoral Fellowship (Tiago Baptista)
  • 2019 - Honorable mention Best Talk, Portuguese Drosophila meeting 2019| Batalha, Portugal, The role of the microenvironment for tumor-like neural stem cell proliferation. (Ana Rita Rebelo) 
  • 2019 - Registration award from SPCE-TC to attend the “11th International Meeting of the Portuguese Society for Stem Cells and Cell Therapies" (Eunice Silva)
  • 2018 - FCT PhD fellowship (Andreia Oliveira)
  • 2017 - FCT PhD fellowship (Eunice Silva)
  • 2017 - FCT PhD fellowship (Marcia Garcez)
  • 2016 - FCT PhD fellowship (Graça Marques)
Research Grant (BI), for the conduct of R&D activities by a PhD student @ Catarina Homem Lab (SAI/2022/08)
Grants

There is an open call for applications for a Research Grant (BI), for the conduct of R&D activities by a PhD student, under reference SAI/2022/08 in the scope of the project HHMI/208581Z/17/Z, at the institution Faculdade de Ciências Médicas|NOVA Medical School (FCM|NMS) from Universidade NOVA de Lisboa (UNL), supported by income from the above mentioned project financed by The Wellcome Trust Limited.

Application deadline: May 30 (until 5:00 PM), 2022.

"Understanding how the brain is formed is one of the best ways to understand its capabilities"

Patrícia Grácio, researcher at NOVA Medical School, talks with  newspaper Observador about her work in neuron differentiation. 

Principal Investigator

Catarina Homem
PI; Scientific Coordinator

Team

Ana Nacarino
Post-doctoral Researcher
Hugo Silva
Post-Doctoral Researcher
Tiago Baptista
Post-Doctoral Researcher
Ana Rebelo
PhD Student
Andreia Costa Oliveira
PhD Student
Eunice Barros da Silva
PhD Student
Graça Marques
PhD Student
Márcia Garcez
PhD Student
Patrícia Grácio
PhD Student
Daniela Lopes
MSc Student
Ana Venda
Researcher, Lab manager