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

Leilei Zhong, Lutian Yao, Robert J. Tower, Yulong Wei, Zhen Miao, Jihwan Park, Rojeshi Shrestha, Luqiang Wang, Wei Yu, Nicholas Holdreith, Yejia Zhang, Wei Tong, Yanqing Gong, Fanxin Long, Jaimo Ahn, Patrick Seale, Katalin Susztak, Mingyao Li, Chider Chen, and Ling Qin

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Sep 18, 2019
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Received Date: 5th September 19

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 (MSCs), the true identity of MSCs and their in vivo bifurcated differentiation routes into osteoblasts and adipocytes remain poorly understood. Here, by employing single cell transcriptome analysis, we identified MSCs and delineated their bi-lineage differentiation paths in young, adult and aging mice. Among several newly discovered mesenchymal subpopulations, one is a distinct population of adipose-lineage cells that we named marrow environment regulating adipose cells (MERAs). MERAs are non-proliferative, post-progenitor cells that express many mature adipocyte markers but are devoid of lipid droplets. They are abundant in the bone marrow of young mice, acting as pericytes and stromal cells that form numerous connections among themselves and with other cells inside bone, including endothelial cells. Genetic ablation of MERAs disrupts marrow vessel structure, promotes de novo bone formation, and prevents marrow vessel recovery after focal radiation injury. Taken together, MERAs represent a unique population of adipose lineage cells that exist only in the bone marrow with critical roles in regulating bone and vessel homeostasis.

Read in full at bioRxiv.

This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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Nature Communications

Nature Research, Springer Nature