Heliyon (Mar 2023)
Obligate role for Rock1 and Rock2 in adult stem cell viability and function
- Arivazhagan Sambandam,
- Elaine Storm,
- Helen Tauc,
- Jason A. Hackney,
- David Garfield,
- Patrick Caplazi,
- John Liu,
- Juan Zhang,
- Hua Zhang,
- Jeff Duggan,
- Surinder Jeet,
- Sarah Gierke,
- Patrick Chang,
- Xiumin Wu,
- Robert Newman,
- Lucinda Tam,
- Tuija Alcantar,
- Lifen Wang,
- Meron Roose-Girma,
- Zora Modrusan,
- Wyne P. Lee,
- Heinrich Jasper,
- Frederic de Sauvage,
- Rajita Pappu
Affiliations
- Arivazhagan Sambandam
- Department of Immunology Discovery, Genentech Inc., South San Francisco, CA, USA
- Elaine Storm
- Department of Molecular Oncology, Genentech Inc., South San Francisco, CA, USA
- Helen Tauc
- Department of Immunology Discovery, Genentech Inc., South San Francisco, CA, USA
- Jason A. Hackney
- Department of Bioinformatics, Genentech Inc., South San Francisco, CA, USA
- David Garfield
- Department of Bioinformatics, Genentech Inc., South San Francisco, CA, USA
- Patrick Caplazi
- Department of Research Pathology, Genentech Inc., South San Francisco, CA, USA
- John Liu
- Department of Translational Immunology, Genentech Inc., South San Francisco, CA, USA
- Juan Zhang
- Department of Translational Immunology, Genentech Inc., South San Francisco, CA, USA
- Hua Zhang
- Department of Translational Immunology, Genentech Inc., South San Francisco, CA, USA
- Jeff Duggan
- Department of Immunology Discovery, Genentech Inc., South San Francisco, CA, USA
- Surinder Jeet
- Department of Translational Immunology, Genentech Inc., South San Francisco, CA, USA
- Sarah Gierke
- Department of Research Pathology, Genentech Inc., South San Francisco, CA, USA
- Patrick Chang
- Department of Research Pathology, Genentech Inc., South San Francisco, CA, USA
- Xiumin Wu
- Department of Translational Immunology, Genentech Inc., South San Francisco, CA, USA
- Robert Newman
- Department of Research Biology, Genentech Inc., South San Francisco, CA, USA
- Lucinda Tam
- Department of Research Biology, Genentech Inc., South San Francisco, CA, USA
- Tuija Alcantar
- Department of Research Biology, Genentech Inc., South San Francisco, CA, USA
- Lifen Wang
- Department of Cancer Immunology, Genentech Inc., South San Francisco, CA, USA
- Meron Roose-Girma
- Department of Research Biology, Genentech Inc., South San Francisco, CA, USA
- Zora Modrusan
- Department of Microchemistry, Proteomics and Lipidomics, Genentech Inc., South San Francisco, CA, USA
- Wyne P. Lee
- Department of Translational Immunology, Genentech Inc., South San Francisco, CA, USA
- Heinrich Jasper
- Department of Immunology Discovery, Genentech Inc., South San Francisco, CA, USA
- Frederic de Sauvage
- Department of Molecular Oncology, Genentech Inc., South San Francisco, CA, USA
- Rajita Pappu
- Department of Immunology Discovery, Genentech Inc., South San Francisco, CA, USA; Corresponding author.
- Journal volume & issue
-
Vol. 9,
no. 3
p. e14238
Abstract
The ability of stem cells to rapidly proliferate and differentiate is integral to the steady-state maintenance of tissues with high turnover such as the blood and intestine. Mutations that alter these processes can cause primary immunodeficiencies, malignancies and defects in barrier function. The Rho-kinases, Rock1 and Rock2, regulate cell shape and cytoskeletal rearrangement, activities essential to mitosis. Here, we use inducible gene targeting to ablate Rock1 and Rock2 in adult mice, and identify an obligate requirement for these enzymes in the preservation of the hematopoietic and gastrointestinal systems. Hematopoietic cell progenitors devoid of Rho-kinases display cell cycle arrest, blocking the differentiation to mature blood lineages. Similarly, these mice exhibit impaired epithelial cell renewal in the small intestine, which is ultimately fatal. Our data reveal a novel role for these kinases in the proliferation and viability of stem cells and their progenitors, which is vital to maintaining the steady-state integrity of these organ systems.
