Single cell transcriptomics identifies a unique adipose lineage cell population that regulates bone marrow environment

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...

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Main Authors: 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
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2020-04-01
Series:eLife
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Online Access:https://elifesciences.org/articles/54695
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author 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
author_facet 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
author_sort Leilei Zhong
collection DOAJ
description 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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spelling doaj.art-e1bde3bf4480496eb8cd45466e5102942024-03-18T14:47:52ZengeLife Sciences Publications LtdeLife2050-084X2020-04-01910.7554/eLife.54695Single cell transcriptomics identifies a unique adipose lineage cell population that regulates bone marrow environmentLeilei Zhong0https://orcid.org/0000-0003-1153-4115Lutian Yao1https://orcid.org/0000-0002-0652-2075Robert J Tower2Yulong Wei3Zhen Miao4https://orcid.org/0000-0002-3255-9517Jihwan Park5https://orcid.org/0000-0002-5728-912XRojesh Shrestha6Luqiang Wang7Wei Yu8https://orcid.org/0000-0001-6705-8264Nicholas Holdreith9Xiaobin Huang10Yejia Zhang11https://orcid.org/0000-0002-7484-8800Wei Tong12Yanqing Gong13Jaimo Ahn14Katalin Susztak15Nathanial Dyment16https://orcid.org/0000-0001-8708-112XMingyao Li17Fanxin Long18Chider Chen19https://orcid.org/0000-0003-2899-1208Patrick Seale20Ling Qin21https://orcid.org/0000-0002-2582-0078Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesDepartment of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States; Department of Orthopaedics, The First Hospital of China Medical University, Shenyang, ChinaDepartment of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesDepartment 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, ChinaDepartment of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, United StatesRenal Electrolyte and Hypertension Division, Department of Medicine and Genetics, University of Pennsylvania, Philadelphia, United StatesRenal Electrolyte and Hypertension Division, Department of Medicine and Genetics, University of Pennsylvania, Philadelphia, United StatesDepartment of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States; Department of Orthopaedics, Shandong University Qilu Hospital, Shandong University, Jinan, ChinaDepartment 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, ChinaDivision of Hematology, Children's Hospital of Philadelphia, Philadelphia, United States; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, United StatesDepartment of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, United StatesDepartment 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 StatesDivision of Hematology, Children's Hospital of Philadelphia, Philadelphia, United States; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, United StatesDivision of Transnational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesDepartment of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesRenal Electrolyte and Hypertension Division, Department of Medicine and Genetics, University of Pennsylvania, Philadelphia, United StatesDepartment of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesDepartment of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, United StatesTranslational Research Program in Pediatric Orthopaedics, The Children's Hospital of Philadelphia, Philadelphia, United StatesDepartment of Oral and Maxillofacial Surgery/Pharmacology, University of Pennsylvania, School of Dental Medicine, Philadelphia, United StatesDepartment of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesDepartment of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesBone 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.https://elifesciences.org/articles/54695adipocytebone marrow mesenchymal stem cellsosteoblastblood vesselsingle cell RNA-seq
spellingShingle 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
Single cell transcriptomics identifies a unique adipose lineage cell population that regulates bone marrow environment
eLife
adipocyte
bone marrow mesenchymal stem cells
osteoblast
blood vessel
single cell RNA-seq
title Single cell transcriptomics identifies a unique adipose lineage cell population that regulates bone marrow environment
title_full Single cell transcriptomics identifies a unique adipose lineage cell population that regulates bone marrow environment
title_fullStr Single cell transcriptomics identifies a unique adipose lineage cell population that regulates bone marrow environment
title_full_unstemmed Single cell transcriptomics identifies a unique adipose lineage cell population that regulates bone marrow environment
title_short Single cell transcriptomics identifies a unique adipose lineage cell population that regulates bone marrow environment
title_sort single cell transcriptomics identifies a unique adipose lineage cell population that regulates bone marrow environment
topic adipocyte
bone marrow mesenchymal stem cells
osteoblast
blood vessel
single cell RNA-seq
url https://elifesciences.org/articles/54695
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