Chimeric blood vessels sustained development of the xenogeneic antler: a unique model for xenogeneic organ generation

Wang, Datao; Wang, Xin; Ba, Hengxing; Ren, Jing; Wang, Zhen; Sun, Hai‐Xi; Chen, Liang; Liu, Chuanyu; Wang, Yusu; Li, Jiping; Liu, Longqi; Liu, Tianbin; Yang, Yunzhi Peter; Liu, Guang‐Hui; Gu, Ying; Li, Chunyi

doi:10.1093/lifemedi/lnac021

Cited by 4 publications

(3 citation statements)

References 9 publications

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“…We subsequently sought to explore in which way HIF-1α contributes to the angiogenic potential of human vascular cells. It is well known that cell migration and in vitro formation of capillary-like tubes are crucial for angiogenesis ( Zhang et al, 2020b ; Ghaffari-Makhmalbaf et al, 2021 ; Wang et al, 2022a ). First, we examined cell migration capability and observed enhanced cellular migration in wild-type (WT) hVECs, hVSMCs, and hMSCs in response to hypoxia compared to normoxic conditions ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Human ESC-derived vascular cells promote vascular regeneration in a HIF-1α dependent manner

et al. 2023

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Hypoxia-inducible factor (HIF-1α), a core transcription factor responding to changes in cellular oxygen levels, is closely associated with a wide range of physiological and pathological conditions. However, its differential impacts on vascular cells types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive. Here, we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells (hESCs) and directed differentiation to generate HIF-1α-deficient human vascular cells including vascular endothelial cells (VECs), vascular smooth muscle cells (VSMCs), and mesenchymal stem cells (MSCs), as a platform for discovering cell type-specific hypoxia-induced response mechanisms. Through comparative molecular profiling across cell types under normoxic and hypoxic conditions, we provide insight into the indispensable role of HIF-1α in the promotion of ischemic vascular regeneration. We found human MSCs to be the vascular cell type most susceptible to HIF-1α deficiency, and that transcriptional inactivation of ANKZF1, an effector of HIF-1α, impaired pro-angiogenic processes. Altogether, our findings deepen the understanding of HIF-1α in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.

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Section: Resultsmentioning

confidence: 99%

Human ESC-derived vascular cells promote vascular regeneration in a HIF-1α dependent manner

et al. 2023

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“…Angiogenesis and initiation of regeneration are two highly coupled processes (Liu et al 2021 ). Initiation of pedicle growth starts from the proliferation of the AP cells, and the proliferating AP cells differentiate into the mixture of osteoblasts and chondroblasts to build up initial pedicle tissue (Li and Suttie 1994a ); at the same time, an ample blood vessel network is rapidly formed around the early growing pedicle tissue, that is why transplanted AP tissue can readily survive and form ectopic or xenogeneic antlers, but PP tissue cannot do so due to the insufficient blood supply (Li et al 2009a ; Li et al 2010 ; Wang et al 2022 ). At the DoPP state, PP cells slowly proliferate and differentiate into osteoblasts and then osteocytes to thicken the pedicle bone in an appositional way.…”

Section: Discussionmentioning

confidence: 99%

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

Wang

et al. 2022

Cell Regen

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Deer antlers constitute a unique mammalian model for the study of both organ formation in postnatal life and annual full regeneration. Previous studies revealed that these events are achieved through the proliferation and differentiation of antlerogenic periosteum (AP) cells and pedicle periosteum (PP) cells, respectively. As the cells resident in the AP and the PP possess stem cell attributes, both antler generation and regeneration are stem cell-based processes. However, the cell composition of each tissue type and molecular events underlying antler development remain poorly characterized. Here, we took the approach of single-cell RNA sequencing (scRNA-Seq) and identified eight cell types (mainly THY1+ cells, progenitor cells, and osteochondroblasts) and three core subclusters of the THY1+ cells (SC2, SC3, and SC4). Endothelial and mural cells each are heterogeneous at transcriptional level. It was the proliferation of progenitor, mural, and endothelial cells in the activated antler-lineage-specific tissues that drove the rapid formation of the antler. We detected the differences in the initial differentiation process between antler generation and regeneration using pseudotime trajectory analysis. These may be due to the difference in the degree of stemness of the AP-THY1+ and PP-THY1+ cells. We further found that androgen-RXFP2 axis may be involved in triggering initial antler full regeneration. Fully deciphering the cell composition for these antler tissue types will open up new avenues for elucidating the mechanism underlying antler full renewal in specific and regenerative medicine in general.

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“…This finding has created new avenues for a number of mechanistic studies. For example, through transplantation of AP to nude mice, we discovered that recipient animals (nude mouse) sustain the development of xenogeneic organs (antler) through chimeric blood vessel network (Wang et al, 2022); AP must interact with skin epidermis to launch antler formation, but this interaction is indirect and relied by the hair follicle dermal papilla cells (Li, Yang, et al, 2009; Sun et al, 2020); and AP has autonomous self‐differentiation attributes, which offers AP an ability to build up an organ (antler) at different niches and in different immune‐deficient animals (nude mouse, Rag‐/‐ IL2‐/‐rat, goat and pig; unpublished). To efficiently carry out these studies using the nude model, we need year‐round supply of the AP tissue.…”

Section: Introductionmentioning

confidence: 99%

A simple method for effective cryopreservation of antlerogenic periosteum of sika deer

Li,

Wang,

Ren

et al. 2023

J Exp Zool Pt A

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Antlerogenic periosteum (AP) is the unique tissue type that gives rise to antlers and their antecedents, the pedicles. Deer antlers are the only mammalian organ that can fully regenerate. Efficient investigation of the mechanism of antler formation and regeneration requires year‐round availability of AP, but naturally AP can only be obtained less than two months in a year. In the present study we took the cryopreservation approach to store the sampled AP in ultra‐low temperature to overcome the limited period of availability. First, we evaluated the suitability of vitrification and cell cryopreservation method for cryopreservation of AP, cell migration status of the AP tissue pieces confirmed that vitrification methods did not work as the only few AP cells migrated out, whereas migrated cell numbers in the cell‐cryo group (conventional method for cryopreservation of cells) were comparable to those of the fresh AP group. To further evaluate the suitability of cell cryopreservation method for AP tissue, AP samples were allocated into three groups based on the different ratios of cryopreservation reagents (dimethyl sulfoxide [DMSO], dulbecco's modified eagle's medium [DMEM] and fetal bovine serum [FBS]): AP‐Cell‐1 (1:4:5), AP‐Cell‐2 (1:2:7) and AP‐Cell‐3 (1:0:9), the results showed that migrated cell number were again comparable to the fresh AP group. There was no significant difference between the cell‐cryo groups (AP‐Cell‐1 and AP‐Cell‐3) and the fresh group: (1) in viability (p > 0.05) through trypan blue staining (91.2%, 90.8%, and 92.4%, respectively); (2) in the attachment day, and all on Day 5 after cell seeding; (3) in cell proliferation rate (p > 0.05) through Cell Counting kit 8 (CCK8) measurement; and (4) in number of the formed clones (Clonogenicity). In the in vivo trials, there was no visible difference in temporal differentiation sequence of the formed xenogeneic antlers between the fresh AP and cryopreserved AP (AP‐Cell‐1 and AP‐Cell‐3). Overall, we found that the AP tissue was well cryopreserved just using the conventional freezing and thawing methods for cells, and their viability and developmental potential comparable to the fresh AP both in vitro and in vivo. The long‐term preservation of the AP tissue is of great significance for the study of the periosteum biology in general and the mechanism underlying xenogeneic generation and regeneration of deer antlers in specific.

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Chimeric blood vessels sustained development of the xenogeneic antler: a unique model for xenogeneic organ generation

Cited by 4 publications

References 9 publications

Human ESC-derived vascular cells promote vascular regeneration in a HIF-1α dependent manner

Human ESC-derived vascular cells promote vascular regeneration in a HIF-1α dependent manner

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

A simple method for effective cryopreservation of antlerogenic periosteum of sika deer

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