Dipeptidyl peptidase-4 cell surface expression marks an abundant adipose stem/progenitor cell population with high stemness in human white adipose tissue

The capacity of adipose stem/progenitor cells (ASCs) to undergo self-renewal and differentiation is crucial for adipose tissue homoeostasis, regeneration and expansion. However, the heterogeneous ASC populations of the adipose lineage constituting adipose tissue are not precisely known. In the present study, we demonstrate that cell surface expression of dipeptidyl peptidase-4 (DPP4)/cluster of differentiation 26 (CD26) subdivides the DLK1−/CD34+/CD45−/CD31− ASC pool of human white adipose tissues (WATs) into two large populations. Ex vivo, DPP4+ ASCs possess higher self-renewal and proliferation capacity and lesser adipocyte differentiation potential than DDP4− ASCs. The knock-down of DPP4 in ASC leads to significantly reduced proliferation and self-renewal capacity, while adipogenic differentiation is increased. Ectopic overexpression of DPP4 strongly inhibits adipogenesis. Moreover, in whole mount stainings of human subcutaneous (s)WAT, we detect DPP4 in CD34+ ASC located in the vascular stroma surrounding small blood vessels and in mature adipocytes. We conclude that DPP4 is a functional marker for an abundant ASC population in human WAT with high proliferation and self-renewal potential and low adipogenic differentiation capacity.脂肪干细胞/祖细胞（adipose stem/progenitor cells, ASCs）的自我更新与分化能力，对于脂肪组织的稳态维持、再生及扩张至关重要。然而，构成脂肪组织的脂肪谱系异质性ASC亚群，其精确组成尚未明确。本研究中，我们证实二肽基肽酶-4（dipeptidyl peptidase-4, DPP4）/分化簇26（cluster of differentiation 26, CD26）的细胞表面表达，可将人类白色脂肪组织（white adipose tissues, WATs）中的DLK1⁻/CD34⁺/CD45⁻/CD31⁻ ASC池划分为两大主要亚群。离体条件下，与DPP4⁻ ASCs相比，DPP4⁺ ASCs具备更高的自我更新与增殖能力，而成脂分化潜能更低。对ASC内的DPP4进行敲降，会显著降低其增殖与自我更新能力，同时增强成脂分化潜能；异位过表达DPP4则可强烈抑制成脂过程。此外，在人类皮下脂肪组织（subcutaneous WAT, sWAT）的全组织染色实验中，我们检测到DPP4表达于小血管周围血管基质中的CD34⁺ ASCs，以及成熟脂肪细胞内。综上，我们得出结论：DPP4是人类白色脂肪组织中一类丰富ASC亚群的功能性标志物，该亚群具备高增殖与自我更新潜能，且成脂分化能力较低。