Prrx1 marks stem cells for bone, white adipose tissue and dermis in adult mice

Huijuan Liu^#^{1

2}, Ping Li^#¹, Shaoyang Zhang^#¹, Jinnan Xiang¹, Ruichen Yang¹, Jiajia Liu¹, Md Shafiquzzaman¹, Soma Biswas¹, Zhanying Wei², Zhenlin Zhang², Xin Zhou³, Feng Yin^{4

5}, Yangli Xie⁶, Stephen P Goff⁷, Lin Chen⁸, Baojie Li^{9

10

11}

Affiliations

¹ Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China.
² Department of Osteoporosis and Bone Diseases, Shanghai Clinical Research Center of Bone Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
³ Institute of Traditional Chinese Medicine and Stem Cell Research, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
⁴ Translational Medical Center for Stem Cell Therapy, Shanghai East Hospital, Tongji University, Shanghai, China.
⁵ Department of Joint and Sports Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China.
⁶ Department Of Wound Repair and Rehabilitation Medicine, Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, China.
⁷ Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, and Department of Microbiology and Immunology, Columbia University, New York, NY, USA.
⁸ Department Of Wound Repair and Rehabilitation Medicine, Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, China. linchen70@163.com.
⁹ Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China. libj@sjtu.edu.cn.
¹⁰ Institute of Traditional Chinese Medicine and Stem Cell Research, Chengdu University of Traditional Chinese Medicine, Chengdu, China. libj@sjtu.edu.cn.
¹¹ Translational Medical Center for Stem Cell Therapy, Shanghai East Hospital, Tongji University, Shanghai, China. libj@sjtu.edu.cn.

^# Contributed equally.

PMID: 36456880
DOI: 10.1038/s41588-022-01227-4

Prrx1 marks stem cells for bone, white adipose tissue and dermis in adult mice

Huijuan Liu et al. Nat Genet. 2022 Dec.

. 2022 Dec;54(12):1946-1958.

doi: 10.1038/s41588-022-01227-4. Epub 2022 Dec 1.

Authors

Affiliations

¹ Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China.
² Department of Osteoporosis and Bone Diseases, Shanghai Clinical Research Center of Bone Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
³ Institute of Traditional Chinese Medicine and Stem Cell Research, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
⁴ Translational Medical Center for Stem Cell Therapy, Shanghai East Hospital, Tongji University, Shanghai, China.
⁵ Department of Joint and Sports Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China.
⁶ Department Of Wound Repair and Rehabilitation Medicine, Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, China.
⁷ Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, and Department of Microbiology and Immunology, Columbia University, New York, NY, USA.
⁸ Department Of Wound Repair and Rehabilitation Medicine, Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, China. linchen70@163.com.
⁹ Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China. libj@sjtu.edu.cn.
¹⁰ Institute of Traditional Chinese Medicine and Stem Cell Research, Chengdu University of Traditional Chinese Medicine, Chengdu, China. libj@sjtu.edu.cn.
¹¹ Translational Medical Center for Stem Cell Therapy, Shanghai East Hospital, Tongji University, Shanghai, China. libj@sjtu.edu.cn.

^# Contributed equally.

PMID: 36456880
DOI: 10.1038/s41588-022-01227-4

Abstract

Specialized connective tissues, including bone and adipose tissues, control various physiological activities, including mineral and energy homeostasis. However, the identity of stem cells maintaining these tissues throughout adulthood remains elusive. By conducting genetic lineage tracing and cell depletion experiments in newly generated knock-in Cre/CreER^T2 lines, we show here that rare Prrx1-expressing cells act as stem cells for bone, white adipose tissue and dermis in adult mice, which are indispensable for the homeostasis and repair of these tissues. Single-cell profiling reveals the cycling and multipotent nature of Prrx1-expressing cells and the stemness of these cells is further validated by transplantation assays. Moreover, we identify the cell surface markers for Prrx1-expressing stem cells and show that the activities of these stem cells are regulated by Wnt signaling. These findings expand our knowledge of connective tissue homeostasis/regeneration and may help improve stem-cell-based therapies.

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References

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Prrx1 marks stem cells for bone, white adipose tissue and dermis in adult mice

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Prrx1 marks stem cells for bone, white adipose tissue and dermis in adult mice

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