Single-cell transcriptome provides novel insights into antler stem cells, a cell type capable of mammalian organ regeneration

Abstract

Antler regeneration, a stem cell-based epimorphic process, has potential as a valuable model for regenerative medicine. A pool of antler stem cells (ASCs) for antler development is located in the antlerogenic periosteum (AP). However, whether this ASC pool is homogenous or heterogeneous has not been fully evaluated. In this study, we produced a comprehensive transcriptome dataset at the single-cell level for the ASCs based on the 10x Genomics platform (scRNA-seq). A total of 4,565 ASCs were sequenced and classified into a large cell cluster, indicating that the ASCs resident in the AP are likely to be a homogeneous population. The scRNA-seq data revealed that tumor-related genes were highly expressed in these homogeneous ASCs:i.e. TIMP1, TMSB10, LGALS1, FTH1, VIM, LOC110126017 and S100A4. Results of screening for stem cell markers suggest that the ASCs may be considered as a special type of stem cell between embryonic (CD9) and adult (CD29, CD90, NPM1 and VIM) stem cells. Our results provide the first comprehensive transcriptome analysis at the single-cell level for the ASCs, and identified only one major cell type resident in the AP and some key stem cell genes, which may hold the key to why antlers, the unique mammalian organ, can fully regenerate once lost.

Cellular and developmental basis of orofacial clefts

“…Another technology, single cell RNA sequencing, has emerged and allows for unprecedented resolution of molecular activities at the level of individual cells. This approach is particularly useful for studying in vivo contexts of developmental mechanisms and has been utilized for investigating cell fate during embryogenesis (Blase, Cao, & Zhong, 2014; Chu et al, 2016; Farrell et al, 2018; Li et al, 2019; Tang et al, 2010; Wagner et al, 2018; Yan et al, 2013) and regeneration (Aztekin et al, 2019; Ba, Wang, Wu, Sun, & Li, 2019; Carr et al, 2019; Johnson, Masias, & Lehoczky, 2020; Leigh et al, 2018; Londono et al, 2020) in various models. Importantly, it will prove invaluable for investigating the contribution of specific cell populations and lineages in the development of OFCs.…”

Single-cell transcriptome reveals core cell populations and androgen-RXFP2 axis involved in deer antler full regeneration

“…S 2 B, C, D, E and Table S 2 ). Among these cell types, THY1 + cells had been defined in our previous studies (Ba et al 2019a ; Dong et al 2020 ; Wang et al 2019 ); progenitor cells were defined for their higher expression of RUNX2 (Prince et al 2001 ), PTN (Dong et al 2021 ), SOX9 (Kim and Im 2011 ), DLX5 (Yang et al 2020 ), TNN (Lui et al 2015 ) and TNC (Liu et al 2019 ), prior to differentiation into osteochondroblasts. SOX9 and RUNX2 are essential for the differentiation of mesenchymal stem cell-derived osteochondro-progenitors towards chondrogenesis and osteogenesis, respectively, but SOX9 is dominant over RUNX2 function in mesenchymal precursors that are destined for a chondrogenic lineage during endochondral ossification (Zhou et al 2006 ).…”

Bioactive Molecular Discovery Using Deer Antlers as a Model of Mammalian Regeneration

“…Genes associated with production traits have been studied with heavy antlers having high expression of genes associated with mineralization ( COL1A1 , COL1A2 , COL3A1 , FN1 , and MT-ATP6 ) . The first single-cell transcriptome analysis of antlerogenic periosteum cells (Figure A) indicates they are likely to be a homogeneous population expressing multiple markers of mesenchymal, embryonic, neural and cancer stem cells . RNA-seq also suggests antler extract treatments may increase chondrocyte activity against oxidative, inflammatory, and immune stresses …”

“…171 The first single-cell transcriptome analysis of antlerogenic periosteum cells (Figure 1A) indicates they are likely to be a homogeneous population expressing multiple markers of mesenchymal, embryonic, neural and cancer stem cells. 172 RNA-seq also suggests antler extract treatments may increase chondrocyte activity against oxidative, inflammatory, and immune stresses. 173…”