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Genetic dissection of clonal lineage relationships with hydroxytamoxifen liposomes

Ryan C Ransom1,2, Deshka S Foster1,2, Ankit Salhotra1,2

  • 1Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, 94305, USA.

Nature Communications
|August 1, 2018
PubMed

Insights

Researchers developed liposomal 4-hydroxytamoxifen (LiTMX) for precise, localized control of CreERT2 recombinase activity in mice. This enables advanced spatial and temporal clonal analysis for diverse biological research applications.

Area of Science:

  • Molecular Biology
  • Genetics
  • Developmental Biology

Background:

  • Precise genetic dissection of tissues is crucial for understanding biological processes and developing therapies.
  • Current methods for clonal analysis often lack spatial and temporal control.
  • Targeting specific cell populations requires advanced genetic tools.

Purpose of the Study:

  • To develop a novel method for localized induction of CreERT2 recombinase activity in vivo.
  • To enable precise, tissue-specific clonal analysis with spatial and temporal control.
  • To provide a versatile tool for lineage tracing and genetic analysis in various biological contexts.

Main Methods:

  • Packaging and delivery of 4-hydroxytamoxifen into liposomes (LiTMX).
  • Utilizing LiTMX for localized induction of CreERT2 recombinase in mice.
  • Applying the method across different tissue types, under homeostasis and post-injury conditions, with various Cre drivers.

Main Results:

  • Demonstrated effective, localized induction of CreERT2 activity.
  • Achieved precise spatial and temporal control in clonal analysis.
  • Showcased high efficiency in lineage tracing and genetic analysis in multiple mouse models and tissues.

Conclusions:

  • LiTMX provides a powerful technology for targeted genetic manipulation in mice.
  • This approach significantly advances capabilities in clonal analysis, lineage tracing, and genetic studies.
  • The methodology is readily applicable to developmental biology, stem cell biology, regenerative medicine, and cancer research.

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