Proteomic analysis of young and old mouse hematopoietic stem cells and their progenitors reveals post-transcriptional regulation in stem cells

Author:

Zaro Balyn W12ORCID,Noh Joseph J12ORCID,Mascetti Victoria L12,Demeter Janos3,George Benson12,Zukowska Monika12,Gulati Gunsagar S12,Sinha Rahul12,Flynn Ryan A4,Banuelos Allison12,Zhang Allison12,Wilkinson Adam C1,Jackson Peter3,Weissman Irving L1256

Affiliation:

1. Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, United States

2. Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University School of Medicine, Stanford, United States

3. Baxter Laboratory, Department of Microbiology and Immunology and Department of Pathology, Stanford University School of Medicine, Stanford, United States

4. Department of Chemistry, Stanford University, Stanford, United States

5. Department of Developmental Biology and the Stanford UC-Berkeley Stem Cell Institute, Stanford, United States

6. Department of Pathology, Stanford University School of Medicine, Stanford, United States

Abstract

The balance of hematopoietic stem cell (HSC) self-renewal and differentiation is critical for a healthy blood supply; imbalances underlie hematological diseases. The importance of HSCs and their progenitors have led to their extensive characterization at genomic and transcriptomic levels. However, the proteomics of hematopoiesis remains incompletely understood. Here we report a proteomics resource from mass spectrometry of mouse young adult and old adult mouse HSCs, multipotent progenitors and oligopotent progenitors; 12 cell types in total. We validated differential protein levels, including confirmation that Dnmt3a protein levels are undetected in young adult mouse HSCs until forced into cycle. Additionally, through integrating proteomics and RNA-sequencing datasets, we identified a subset of genes with apparent post-transcriptional repression in young adult mouse HSCs. In summary, we report proteomic coverage of young and old mouse HSCs and progenitors, with broader implications for understanding mechanisms for stem cell maintenance, niche interactions and fate determination.

Funder

California Institute of Regenerative Medicine

Virginia and D.K. Ludwig Fund for Cancer Research

NIH

National Heart, Lung, and Blood Institute

American Cancer Society

National Cancer Institute

Damon Runyon Cancer Research Foundation

Leukemia and Lymphoma Society

American Society of Hematology

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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