A mosaic analysis system with Cre or Tomato expression in the mouse.

Journal Article (Journal Article)

Somatic mutations are major genetic contributors to cancers and many other age-related diseases. Many disease-causing somatic mutations can initiate clonal growth prior to the appearance of any disease symptoms, yet experimental models that can be used to examine clonal abnormalities are limited. We describe a mosaic analysis system with Cre or Tomato (MASCOT) for tracking mutant cells and demonstrate its utility for modeling clonal hematopoiesis. MASCOT can be induced to constitutively express either Cre-GFP or Tomato for lineage tracing of a mutant and a reference group of cells simultaneously. We conducted mosaic analysis to assess functions of the Id3 and/or Tet2 gene in hematopoietic cell development and clonal hematopoiesis. Using Tomato-positive cells as a reference population, we demonstrated the high sensitivity of this system for detecting cell-intrinsic phenotypes during short-term or long-term tracking of hematopoietic cells. Long-term tracking of Tet2 mutant or Tet2/Id3 double-mutant cells in our MASCOT model revealed a dynamic shift from myeloid expansion to lymphoid expansion and subsequent development of lymphoma. This work demonstrates the utility of the MASCOT method in mosaic analysis of single or combined mutations, making the system suitable for modeling somatic mutations identified in humans.

Full Text

Duke Authors

Cited Authors

  • Wang, Q; Lin, Y-Y; Zhang, B; Wu, J; Roy, S; Ratiu, JJ; Xu, Y; Dai, M; Hale, LP; Xiong, Y; Li, Q-J; Zhuang, Y

Published Date

  • November 10, 2020

Published In

Volume / Issue

  • 117 / 45

Start / End Page

  • 28212 - 28220

PubMed ID

  • 33106431

Pubmed Central ID

  • PMC7668046

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.2014308117

Language

  • eng

Conference Location

  • United States