eLife (Apr 2020)
Single cell transcriptomics identifies a unique adipose lineage cell population that regulates bone marrow environment
- Leilei Zhong,
- Lutian Yao,
- Robert J Tower,
- Yulong Wei,
- Zhen Miao,
- Jihwan Park,
- Rojesh Shrestha,
- Luqiang Wang,
- Wei Yu,
- Nicholas Holdreith,
- Xiaobin Huang,
- Yejia Zhang,
- Wei Tong,
- Yanqing Gong,
- Jaimo Ahn,
- Katalin Susztak,
- Nathanial Dyment,
- Mingyao Li,
- Fanxin Long,
- Chider Chen,
- Patrick Seale,
- Ling Qin
Affiliations
- Leilei Zhong
- ORCiD
- Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
- Lutian Yao
- ORCiD
- Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States; Department of Orthopaedics, The First Hospital of China Medical University, Shenyang, China
- Robert J Tower
- Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
- Yulong Wei
- Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States; Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Zhen Miao
- ORCiD
- Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, United States
- Jihwan Park
- ORCiD
- Renal Electrolyte and Hypertension Division, Department of Medicine and Genetics, University of Pennsylvania, Philadelphia, United States
- Rojesh Shrestha
- Renal Electrolyte and Hypertension Division, Department of Medicine and Genetics, University of Pennsylvania, Philadelphia, United States
- Luqiang Wang
- Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States; Department of Orthopaedics, Shandong University Qilu Hospital, Shandong University, Jinan, China
- Wei Yu
- ORCiD
- Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States; Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Nicholas Holdreith
- Division of Hematology, Children's Hospital of Philadelphia, Philadelphia, United States; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, United States
- Xiaobin Huang
- Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, United States
- Yejia Zhang
- ORCiD
- Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States; Department of Physical Medicine and Rehabilitation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States; Translational Musculoskeletal Research Center (TMRC), Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, United States
- Wei Tong
- Division of Hematology, Children's Hospital of Philadelphia, Philadelphia, United States; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, United States
- Yanqing Gong
- Division of Transnational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
- Jaimo Ahn
- Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
- Katalin Susztak
- Renal Electrolyte and Hypertension Division, Department of Medicine and Genetics, University of Pennsylvania, Philadelphia, United States
- Nathanial Dyment
- ORCiD
- Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
- Mingyao Li
- Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, United States
- Fanxin Long
- Translational Research Program in Pediatric Orthopaedics, The Children's Hospital of Philadelphia, Philadelphia, United States
- Chider Chen
- ORCiD
- Department of Oral and Maxillofacial Surgery/Pharmacology, University of Pennsylvania, School of Dental Medicine, Philadelphia, United States
- Patrick Seale
- Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
- Ling Qin
- ORCiD
- Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
- DOI
- https://doi.org/10.7554/eLife.54695
- Journal volume & issue
-
Vol. 9
Abstract
Bone marrow mesenchymal lineage cells are a heterogeneous cell population involved in bone homeostasis and diseases such as osteoporosis. While it is long postulated that they originate from mesenchymal stem cells, the true identity of progenitors and their in vivo bifurcated differentiation routes into osteoblasts and adipocytes remain poorly understood. Here, by employing large scale single cell transcriptome analysis, we computationally defined mesenchymal progenitors at different stages and delineated their bi-lineage differentiation paths in young, adult and aging mice. One identified subpopulation is a unique cell type that expresses adipocyte markers but contains no lipid droplets. As non-proliferative precursors for adipocytes, they exist abundantly as pericytes and stromal cells that form a ubiquitous 3D network inside the marrow cavity. Functionally they play critical roles in maintaining marrow vasculature and suppressing bone formation. Therefore, we name them marrow adipogenic lineage precursors (MALPs) and conclude that they are a newly identified component of marrow adipose tissue.
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