Cell Reprogramming and Developmental Hematopoiesis

Filipe Pereira

PhD, Group Leader

The focus of our laboratory is to understand the molecular determinants underlying cell reprogramming and hematopoietic specification. In humans, the multiple differentiated cell states are normally stable and inherited through cell division. Under certain conditions, cell fate can, however, be modified or reversed. Cell reprogramming can be achieved experimentally in different ways, including nuclear transfer, cell fusion or expression of transcription factors. The emergent ability to directly reprogram somatic cells into desired hematopoietic cell-types is opening avenues to the discovery of new therapies for immune and blood diseases. Our approach focuses on Hematopoietic Stem Cells (HSCs) for their remarkable regenerative potential and Dendritic Cells (DCs) as key mediators of immunity. Aims:

  1. To understand at the molecular level how hematopoietic cellular identities are specified during development employing cellular reprogramming;
  2. To use this knowledge to allow the generation of patient-specific hematopoietic and immune cells for regenerative medicine and immunotherapy;
  3. Our research will increase the understanding of the intrinsic determinants underlying hematopoietic progenitor and effector cell developmental specification. This knowledge may allow the re-creation of these unique cell identities from any human cell. Ultimately, we believe that our research will contribute to personalized hematopoietic regeneration by employing human programmed HSCs for patient-specific cell transplantation. In addition, DC reprogramming is allowing us to develop new ways to modulate the immune response. This represents a unique opportunity to merge the field of cell reprogramming and cancer immunotherapy and may result in the development of powerful new therapeutics for cancer and other diseases resulting from a dysfunctional immune system.

Group Members

Group members are: Filipe Pereira (PhD, Group Leader), Alexandra Ferreira, Cristina Pires (PhD), Fábio Rosa, Inês Caiado, Luís Oliveira, Marta Pinto (PhD), Rita Alves, Susana Pedreiro.

Selected Publications

Pires, C.F., Rosa, F.F., Pereira, C.F. (2019) Understanding and modulating immunity with cell reprogramming. Frontiers in Immunology in press.

Silvério-Alves, R., Gomes, A.M., Kurochkin, I., Moore, K.A., Pereira, C.F. (2019) Hemogenic Reprogramming of Human Fibroblasts by Enforced Expression of Transcription Factors. JoVE. Nov 4;(153).

Rosa, F.F. *, Pires, C.F. *, Kurochkin, I., Ferreira, A.G., Gomes, A.M., Palma, L.G., Shaiv, K., Solanas, L., Azenha, C., Papatsenko, D., Schulx, O., Reis e Sousa, C., Pereira, C.F. (2018) Direct reprogramming of fibroblasts into antigen-presenting dendritic cells. Science Immunology 7, 3(30). *equal contribution. -Cover Science Immunology issue December 2018. Preview by Yona & Mildner, issue December 2018.

Gomes, A.M., Kurochkin, I., Chang, B.; Daniel, M., Law, K., Satija, N., Lachmann, A., Wang, Z., Ferreira, L., Ma’ayan, A., Chen, B.K., Papatsenko, D., Lemischka, I.R., Moore, K.A., Pereira, C.F. (2018) Cooperative Transcription Factor Induction Mediates Hemogenic Reprogramming. Cell Reports 25, 2821-25.

Kirkeby, A., Perlmann, T., Pereira, C. F *. (2016) The stem cell niche finds its true north. Development. *corresponding author.

Pereira, C.F.*; Chang, B.; Papatsenko, D.; Gomes, A.; Bernitz, B.; Niu, X.; Swiers, G.; Azzoni, E.; Brujin M.F.T.R.; Schaniel, C.; Lemischka, I.R.; Moore, K.A. (2016) Identification of Hemogenic Precursors in Placenta that Give Rise to Definitive Hematopoietic Stem Cells In Vivo is Informed by Hematopoietic Reprogramming In Vitro. Developmental Cell 36, 525-39. *corresponding author.

Pereira, C.F. *, Chang, B., Qiu, J., Niu, X., Papatsenko D., Hendry, C.E., Clark, N.R., Nomura-Kitabayashi, A., Kovacic, J., Ma’ayan A., Schaniel C., Lemischka, I.R., Moore, K.A. (2013) Induction of a Hemogenic Program in Mouse Fibroblasts. Cell Stem Cell 13, 205-18. *corresponding author. -Cover Cell Stem Cell issue August 2013. Preview by Pfaff & Cantz, 2013. -Highlighted in Molecular Therapy 21, 1291 (2013), Stem cells Translational Medicine News section June 2013.
— Recommended by the Faculty of 1000.

Pereira C.F. *, Lemischka I.R., Moore K.A. (2012) Reprogramming cell fates: insights from combinatorial approaches. Ann. N. Y. Acad. Sci. 1266, 7-17. *corresponding author.

Pereira, C.F., Piccolo, F.M., Tsubouchi, T., Sauer, S., Ryan, N.K., Bruno, L., Landeira, D., Santos, J., Banito, A., Gil, J., Koseki, H., Merkenschlager, M., Fisher, A.G. (2010). ESCs require PRC2 to direct the successful reprogramming of differentiated cells towards pluripotency. Cell Stem Cell. 6, 547-556.
— Recommended by the Faculty of 1000.

Selected Projects

FCT project PTDC/BIM-MED/0075/2014. Mechanisms underlying hemogenic induction in human fibroblasts. (2016-2019). FCT, Portugal. PI: Filipe Pereira.

Generating dendritic cells by direct cell reprogramming.

FCT project. Reconstructing the program of gastric and colorectal cancer stem cells.(2018-2021). FCT, Portugal. Co-PI: Filipe Pereira.

FCT Project 02/SAICT/2017. Generating antigen presenting cells by direct cellular reprogramming. (2018-2021). FCT, Portugal. PI: Filipe Pereira.

FCT PAC consortium CANCEL_STEM. Estaminalidade das células do cancro: um desafio e uma oportunidade para avançar no tratamento em Oncologia. (2017-2019). FCT, Portugal. Co-PI: Filipe Pereira.

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