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Regulation of extreme plasticity in planarian stem cells by mRNA modifications

Objective

Planarians are freshwater flatworms that can regenerate any part of their body including an entire head. A single transplanted planarian pluripotent stem cell can rescue a lethally irradiated animal. Hence, the extreme plasticity of planarian stem cells (neoblasts) is critical for regeneration. Despite intensive research, we still do not understand how cellular mechanisms that regulate neoblast homeostasis are integrated to facilitate regeneration. In a preliminary study, I discovered that chemical modifications of nucleic acids are critical for normal neoblast function, and that animals lacking this activity fail to regenerate. This extreme neoblast phenotype suggests that these highly conserved base modifications are crucial regulators of stem cell homeostasis. In this project, I will dissect the functions of nucleic acid base modifications in vivo using high-throughput gene function screening, single cell RNA sequencing, and molecular biology methods. I will establish a mechanistic foundation for understanding the regulation of stem cell plasticity and regeneration. In particular, we will (1) analyze the functions of genes encoding nucleic acid modifiers and use planarians as a platform for discovery of unknown players, (2) elucidate the regulatory roles of the base modification machinery on stem cell function, (3) investigate the dynamics of nucleic acid base modification landscape in planarian stem cell physiology and injury. My approach will generate a systems level understanding of nucleic acid modification-based regulation on stem cell homeostasis, an emerging theme in stem cell research. The impact of these findings are far reaching and would become the basis for a deeper understanding of fundamental stem cell biology, including mammalian physiology and pathology.

Host institution

TEL AVIV UNIVERSITY

Address

Ramat Aviv
69978 Tel Aviv

Israel

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 1 487 500

Beneficiaries (1)

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TEL AVIV UNIVERSITY

Israel

EU Contribution

€ 1 487 500

Project information

Grant agreement ID: 853640

Status

Ongoing project

  • Start date

    1 November 2019

  • End date

    31 October 2024

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 1 487 500

  • EU contribution

    € 1 487 500

Hosted by:

TEL AVIV UNIVERSITY

Israel