Single-cell Transcriptomics of LepR-positive Skeletal Cells Reveals Heterogeneous Stress-dependent Stem and Progenitor Pools

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2021 Dec 27

PMID 34957577

Citations 36

Authors

Chunyang Mo

Jingxin Guo

Jiachen Qin

Xiaoying Zhang

Yuxi Sun

Hanjing Wei

Dandan Cao

Yiying Zhang

Chengchen Zhao

Yanhong Xiong

Yong Zhang

Yao Sun

Li Shen

Rui Yue

Affiliations

Soon will be listed here.

Abstract

Leptin receptor (LepR)-positive cells are key components of the bone marrow hematopoietic microenvironment, and highly enrich skeletal stem and progenitor cells that maintain homeostasis of the adult skeleton. However, the heterogeneity and lineage hierarchy within this population has been elusive. Using genetic lineage tracing and single-cell RNA sequencing, we found that Lepr-Cre labels most bone marrow stromal cells and osteogenic lineage cells in adult long bones. Integrated analysis of Lepr-Cre-traced cells under homeostatic and stress conditions revealed dynamic changes of the adipogenic, osteogenic, and periosteal lineages. Importantly, we discovered a Notch3 bone marrow sub-population that is slow-cycling and closely associated with the vasculatures, as well as key transcriptional networks promoting osteo-chondrogenic differentiation. We also identified a Sca-1 periosteal sub-population with high clonogenic activity but limited osteo-chondrogenic potential. Together, we mapped the transcriptomic landscape of adult LepR stem and progenitor cells and uncovered cellular and molecular mechanisms underlying their maintenance and lineage specification.

Citing Articles

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