Gli1+ Cells Couple with Type H Vessels and Are Required for Type H Vessel Formation
Authors: Bing-Dong Sui
Xiao-Lin Xu
Li-Hui Bao
Cheng-Hu Hu
Jiang-Tao Guan
Kai Chen
Chen-Xi Zheng
De-Hua Li
Meng Bai
Ji Chen
An-Qi Liu
Meng Li
Yan Jin
Tao Zhou
Journal: Stem Cell Reports (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Gli1; angiogenesis; bone; mesenchymal stem cells; type H vessels.
Affiliations: State Key Laboratory of Military Stomatology& National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, 145 West Changle Road, Xi'an, Shaanxi 710032, China; Department of Oral Implantology, School of Stomatology, Fourth Military Medical University, Xi'an, Shannxi 710032, China., State Key Laboratory of Military Stomatology& National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, 145 West Changle Road, Xi'an, Shaanxi 710032, China., State Key Laboratory of Military Stomatology& National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, 145 West Changle Road, Xi'an, Shaanxi 710032, China; Xi'an Institute of Tissue Engineering and Regenerative Medicine, Xi'an, Shaanxi 710032, China., Department of Oral Implantology, School of Stomatology, Fourth Military Medical University, Xi'an, Shannxi 710032, China. Electronic address: ., State Key Laboratory of Military Stomatology& National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, 145 West Changle Road, Xi'an, Shaanxi 710032, China. Electronic address: ., State Key Laboratory of Military Stomatology& National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, 145 West Changle Road, Xi'an, Shaanxi 710032, China; Xi'an Institute of Tissue Engineering and Regenerative Medicine, Xi'an, Shaanxi 710032, China. Electronic address: .

Abstract:  Mesenchymal stem/stromal cells (MSCs) reside in the perivascular niche and modulate tissue/organ homeostasis; however, little is known about whether and how their localization and function are linked. Particularly, whether specific MSC subsets couple with and regulate specialized vessel subtypes is unclear. Here, we show that Gli1+ cells, which are a subpopulation of MSCs couple with and regulate a specialized form of vasculature. The specific capillaries, i.e., CD31hiEMCNhi type H vessels, are the preferable vascular subtype which Gli1+ cells are adjacent to in bone. Gli1+ cells are further identified to be phenotypically coupled with type H endothelium during bone growth and defect healing. Importantly, Gli1+ cell ablation inhibits type H vessel formation associated with suppressed bone generation and regeneration. Mechanistically, Gli1+ cells initiate angiogenesis through Gli and HIF-1Œ± signaling. These findings suggest a morphological and functional framework of Gli1+ cells modulating coupled type H vasculature for tissue homeostasis and regenerative repair. 

Retracted: No

PubPeer comments:
 Two images in Figure 4H appear to show overlapping regions after rotation, but appear to be described differently. The same issue seems to be true for the images of the merged fields. ***  *** Close-up  , 
 Dear Dr. Actinopolyspora biskrensis, Thank you very much for your careful reading of our article. Please see below my response to your comments. Best wishes, Yan Jin , 
 The metaphysis is the critical zone for bone growth, which is recognized to locate beneath the growth palate and above the midshaft region known as the diaphysis. However, the accurate u201cborder lineu201d between the metaphysis and the diaphysis does not exist, and the detailed region for metaphysis cannot be defined within a certain range. Particularly, as bone changes with the advancing age and various extrinsic cues, one should treat the metaphysis versus diaphysis regions as dynamic rather than accurate zones.  Structure of the bone (from Wikipedia)  Extended Data Figure 6C from Kusumbe AP, et al. Nature, 2014. PMID: 24646994. The original discovery of type H vessels. In the experimental work, the metaphysis is often characterized with abundant trabecular bones which are nearly vertical to the growth palate in the neck portion of the long bones, selected at about 200 u03bcm in length in our study. When taken photos, which were square because of the microscopy settings, the diaphysis region beneath inevitabbly appeared in the vision.  Our images of Hif-1u03b1 staining (GP, growth palate; MP, metaphysis; DP, diaphysis)  Figure 1d and Extended Data Figure 4a from Kusumbe AP, et al. Nature, 2014. PMID: 24646994. As to why the data were rotated, it was because the metaphysis regions were taken with the growth palate heading below. To meet the common criteria, we rotated the metaphysis pictures to make the growth palate heading up.   The processing of the Hif-1u03b1 images. Please check the above information. Thank you again for your careful reading of our article. , 
 #3 Thank you. Your detailed reply alleviates my concern. Much appreciated. ,