No abstract

Poor graft function (PGF), characterized by pancytopenia, is a severe complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our prior works (BBMT 2013; BMT 2016; Blood 2016; Haematologica 2022) reported that the decreased and dysfunctional bone marrow (BM) endothelial progenitor cells (EPCs), a crucial cellular component in moderating hematopoietic stem cells (HSCs) in the BM microenvironment, were implicated in the pathogenesis of PGF. Moreover, prophylactic approaches to rescue aberrant BM EPCs in PGF patients could promote hematopoietic reconstitution after allo-HSCT (Blood Advances 2019; BMC Med 2022), further confirming the vital role of BM EPCs in regulating hematopoietic recovery post-allo-HSCT. However, the underlying mechanism by which EPCs mediate HSCs remains to be elucidated. Peroxisome proliferator-activated receptors (PPARs), consisting of three isotypes, PPARα , PPARγ and PPARδ , act as key members of the nuclear receptor superfamily of transcription factors that govern a variety of biological processes, such as cell metabolism, proliferation, differentiation and survival. Recently, PPARδ , but not PPARα or PPARγ , was reported to be the predominant expressed isotype of PPARs in BM HSCs and plays a critical role in regulating HSC activities, including maintenance of stemness and asymmetric division. Although PPARδ plays an essential role in HSCs, its effect on BM EPCs, the indispensable niche for HSCs, is largely unknown.