Programming human cell fate: overcoming challenges and unlocking potential through technological breakthroughs

Author:

Lin Hsiu-Chuan1ORCID,Makhlouf Aly2ORCID,Vazquez Echegaray Camila3ORCID,Zawada Dorota456ORCID,Simões Filipa78ORCID

Affiliation:

1. ETH Zürich 1 Department of Biosystems Science and Engineering , , 4057 Basel , Switzerland

2. University of Cambridge 2 MRC Laboratory of Molecular Biology , , Cambridge CB2 0QH , UK

3. Lund Stem Cell Centre, Wallenberg Centre for Molecular Medicine, Lund University 3 Molecular Medicine and Gene Therapy , , 221 84 Lund , Sweden

4. Klinikum rechts der Isar, Technical University of Munich, School of Medicine and Health 4 First Department of Medicine, Cardiology , , 81675 Munich , Germany

5. German Center for Cardiovascular Research (DZHK), Munich Heart Alliance 5 , 80636 Munich , Germany

6. Klinikum rechts der Isar, Technical University of Munich, School of Medicine and Health 6 Regenerative Medicine in Cardiovascular Diseases, First Department of Medicine , , 81675 Munich , Germany

7. Institute of Developmental and Regenerative Medicine 7 Department of Physiology, Anatomy and Genetics , , , Oxford OX3 7TY , UK

8. University of Oxford 7 Department of Physiology, Anatomy and Genetics , , , Oxford OX3 7TY , UK

Abstract

ABSTRACT In recent years, there have been notable advancements in the ability to programme human cell identity, enabling us to design and manipulate cell function in a Petri dish. However, current protocols for generating target cell types often lack efficiency and precision, resulting in engineered cells that do not fully replicate the desired identity or functional output. This applies to different methods of cell programming, which face similar challenges that hinder progress and delay the achievement of a more favourable outcome. However, recent technological and analytical breakthroughs have provided us with unprecedented opportunities to advance the way we programme cell fate. The Company of Biologists’ 2023 workshop on ‘Novel Technologies for Programming Human Cell Fate’ brought together experts in human cell fate engineering and experts in single-cell genomics, manipulation and characterisation of cells on a single (sub)cellular level. Here, we summarise the main points that emerged during the workshop's themed discussions. Furthermore, we provide specific examples highlighting the current state of the field as well as its trajectory, offering insights into the potential outcomes resulting from the application of these breakthrough technologies in precisely engineering the identity and function of clinically valuable human cells.

Funder

Human Frontier Science Program

Cambridge Trust

H2020 Marie Skłodowska-Curie Actions

European Research Council

Deutsche Forschungsgemeinschaft

University of Oxford

British Heart Foundation

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

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