Cell populations and their interplay provide the basis of a cell‐based regenerative construct. Serum‐free preconditioning can overcome the less predictable behavior of serum expanded progenitor cells, but the underlying mechanism and how this is reflected in vivo remains unknown. Herein, the cellular and molecular changes associated with a cellular phenotype shift induced by serum‐free preconditioning of human periosteum‐derived cells were investigated. Following BMP‐2 stimulation, preconditioned cells displayed enhanced in vivo bone forming capacity, associated with an adapted cellular metabolism together with an elevated expression of BMPR2. Single‐cell RNA sequencing confirmed the activation of pathways and transcriptional regulators involved in bone development and fracture healing, providing support for the augmentation of specified skeletal progenitor cell populations. The reported findings illustrate the importance of appropriate in vitro conditions for the in vivo outcome. In addition, BMPR2 represents a promising biomarker for the enrichment of skeletal progenitor cells for in vivo bone regeneration.

中文翻译：

---

具有增强的体内骨形成能力的体外培养的人骨骼祖细胞的单细胞表征和代谢谱分析。

细胞群体及其相互作用为基于细胞的再生构建提供了基础。无血清预处理可以克服血清扩增的祖细胞难以预测的行为，但是其潜在机制及其在体内的反映方式尚不清楚。在本文中，研究了由人骨膜衍生细胞的无血清预处理引起的与细胞表型转变有关的细胞和分子变化。在BMP-2刺激后，预处理细胞显示出增强的体内骨形成能力，与适应的细胞代谢以及BMPR2的表达升高有关。单细胞RNA测序证实了参与骨骼发育和骨折愈合的途径和转录调节因子的激活，为增加特定骨骼祖细胞群提供支持。报道的发现说明了适当的体外条件对于体内结果的重要性。此外，BMPR2代表了一种有前途的生物标志物，可丰富骨骼祖细胞用于体内骨骼再生。