puc-header

Distinct CSF1 Micro-Environments Maintain Monocytes within a Perivascular Bone Marrow Niche

42 Pages Posted: 26 May 2020 Sneak Peek Status: Under Review

See all articles by Takuo Emoto

Takuo Emoto

University Health Network - Toronto General Research Institute (UHN Research)

Jessie Lu

University of Toronto - Department of Laboratory Medicine and Pathobiology

Tharini Sivasubramaniyam

University Health Network - Toronto General Research Institute (UHN Research)

Hassaan Maan

Peter Munk Cardiac Centre

Marwan Althagafi

University of Toronto - Department of Laboratory Medicine and Pathobiology

Fred Fu

University Health Network - STTARR Innovation Centre

Felix Chiu

University of Toronto - Department of Laboratory Medicine and Pathobiology

Shaun Pacheco

University Health Network - Toronto General Research Institute (UHN Research)

Angela Li

University of Toronto - Department of Immunology

Aniqa Khan

University of Toronto - Department of Immunology

Sharon Hyduk

University Health Network - Toronto General Research Institute (UHN Research)

Trevor McKee

University Health Network - STTARR Innovation Centre

Jean Jiang

The University of Texas at San Antonio - Department of Biochemistry and Structural Biology

Peter Libby

Harvard University - Department of Medicine

Bo Wang

Peter Munk Cardiac Centre

Barry B. Rubin

Peter Munk Cardiac Centre

Myron Cybulsky

University of Toronto - Department of Laboratory Medicine and Pathobiology; University Health Network - Toronto General Research Institute (UHN Research); Peter Munk Cardiac Centre

Clinton S. Robbins

University of Toronto - Department of Laboratory Medicine and Pathobiology; University of Toronto - Department of Immunology; University Health Network - Toronto General Research Institute (UHN Research); Peter Munk Cardiac Centre

More...

Abstract

The bone marrow niche factors that sustain monocytes – phagocytes with complex functions in the circulation and peripheral tissues – and the functionally important cells that produce them, are poorly defined. Here, we conditionally deleted macrophage colony stimulating factor 1 (Csf1) in adult mice and show that CSF1 regulated differentiation and survival of monocytes and their precursor cells independent of its effects on bone development. Specifically, CSF1 produced by sinusoidal endothelial cells (ECs) but not leukocytes or stromal cells selectively maintained abundance of nonclassical Ly6Cnegative monocytes. Ly6Chigh monocytes, on the other hand, required CSF1 produced by ECs as well as leptin receptor (Lepr)-expressing perivascular stromal cells. Importantly, osteoblast-derived CSF1 critically supported bone formation and hematopoiesis during early development but did not contribute to maintenance of monocytes in adulthood. Our findings reveal classical and non-classical monocytes receive support by distinct cellular sources of CSF1 within a perivascular bone marrow niche.

Keywords: bone marrow niche, monocyte, CSF1, endothelial cell, perivascular stromal cell

Suggested Citation

Emoto, Takuo and Lu, Jessie and Sivasubramaniyam, Tharini and Maan, Hassaan and Althagafi, Marwan and Fu, Fred and Chiu, Felix and Pacheco, Shaun and Li, Angela and Khan, Aniqa and Hyduk, Sharon and McKee, Trevor and Jiang, Jean and Libby, Peter and Wang, Bo and Rubin, Barry B. and Cybulsky, Myron and Robbins, Clinton S., Distinct CSF1 Micro-Environments Maintain Monocytes within a Perivascular Bone Marrow Niche. Available at SSRN: https://ssrn.com/abstract=3596597 or http://dx.doi.org/10.2139/ssrn.3596597
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Takuo Emoto

University Health Network - Toronto General Research Institute (UHN Research) ( email )

200 Elizabeth Street
Toronto, ON M5G 2C4
Canada

Jessie Lu

University of Toronto - Department of Laboratory Medicine and Pathobiology

Medical Sciences Building, 6th Floor
1 King's College Circle
Toronto, Ontario M5S 1A8
Canada

Tharini Sivasubramaniyam

University Health Network - Toronto General Research Institute (UHN Research) ( email )

200 Elizabeth Street
Toronto, ON M5G 2C4
Canada

Hassaan Maan

Peter Munk Cardiac Centre ( email )

Toronto, Ontario
Canada

Marwan Althagafi

University of Toronto - Department of Laboratory Medicine and Pathobiology ( email )

Medical Sciences Building, 6th Floor
1 King's College Circle
Toronto, Ontario M5S 1A8
Canada

Fred Fu

University Health Network - STTARR Innovation Centre ( email )

101 College Street
Toronto, ON M5G 1L7 ON M5G 1L7
Canada

Felix Chiu

University of Toronto - Department of Laboratory Medicine and Pathobiology ( email )

Medical Sciences Building, 6th Floor
1 King's College Circle
Toronto, Ontario M5S 1A8
Canada

Shaun Pacheco

University Health Network - Toronto General Research Institute (UHN Research)

200 Elizabeth Street
Toronto, ON M5G 2C4
Canada

Angela Li

University of Toronto - Department of Immunology

1 King's College Circle
Medical Sciences Building, Room 7207
Toronto, Ontario M5S 1A8
Canada

Aniqa Khan

University of Toronto - Department of Immunology ( email )

1 King's College Circle
Medical Sciences Building, Room 7207
Toronto, Ontario M5S 1A8
Canada

Sharon Hyduk

University Health Network - Toronto General Research Institute (UHN Research) ( email )

200 Elizabeth Street
Toronto, ON M5G 2C4
Canada

Trevor McKee

University Health Network - STTARR Innovation Centre ( email )

101 College Street
Toronto, ON M5G 1L7 ON M5G 1L7
Canada

Jean Jiang

The University of Texas at San Antonio - Department of Biochemistry and Structural Biology ( email )

ONE UTSA Circle
San Antonio, TX 78249
United States

Peter Libby

Harvard University - Department of Medicine

Boston, MA 02115
United States

Bo Wang

Peter Munk Cardiac Centre

Toronto, Ontario
Canada

Barry B. Rubin

Peter Munk Cardiac Centre

585 University Avenue
Toronto, ON M5G 2N2
Canada

Myron Cybulsky

University of Toronto - Department of Laboratory Medicine and Pathobiology

Medical Sciences Building, 6th Floor
1 King's College Circle
Toronto, Ontario M5S 1A8
Canada

University Health Network - Toronto General Research Institute (UHN Research)

200 Elizabeth Street
Toronto, ON M5G 2C4
Canada

Peter Munk Cardiac Centre

585 University Avenue
Toronto, ON M5G 2N2
Canada

Clinton S. Robbins (Contact Author)

University of Toronto - Department of Laboratory Medicine and Pathobiology ( email )

Medical Sciences Building, 6th Floor
1 King's College Circle
Toronto, Ontario M5S 1A8
Canada

University of Toronto - Department of Immunology ( email )

1 King's College Circle
Medical Sciences Building, Room 7207
Toronto, Ontario M5S 1A8
Canada

University Health Network - Toronto General Research Institute (UHN Research) ( email )

200 Elizabeth Street
Toronto, ON M5G 2C4
Canada

Peter Munk Cardiac Centre ( email )

585 University Avenue
Toronto, ON M5G 2N2
Canada

Click here to go to Cell.com

Paper statistics

Abstract Views
114
Downloads
10