Adult ovarian tissues or biopsies isolated from patients prior to chemotherapy or irradiation can reconstitute ovarian functions when transplanted either in the abdomen or subcutaneously. Subcutaneously transplantation avoids invasive surgery and potential risks associated with internal procedures. We investigated whether functional ovaries could develop subcutaneously from early E12.5 fetal gonads without entering meiosis in mouse model. Unexpectedly, the subcutaneously transplanted fetal gonads failed to undergo folliculogenesis in the recipient mice. The transplanted gonads experienced meiotic deficiency and exhibited significant defects in DNA repair and recombination, increased apoptosis levels. Meiotic defects in the subcutaneous grafts were partly attributable to variations in temperature and oxygen concentration. However, completion of meiotic prophase I was effectively achieved through in vitro culture of the gonads at 37℃. Subsequently, the in vitro cultured E12.5 gonads, following subcutaneous transplantation, became competent in folliculogenesis, restoring endocrine functions. This finding may have implications for rejuvenating ovarioids from fetal gonad-like cells using pluripotent stem cell technologies, as well as for enhancing endocrine recovery and health span.

During early embryonic development, particularly in the transition from totipotency to pluripotency, energy metabolism is closely linked to cell fate. However, the essential regulators of energy metabolism in this transition remain unclear. In this study, we reveal that Tcl1 influences energy metabolic characteristics and regulates the totipotency-pluripotency transition. Our findings demonstrate that the absence of Tcl1 triggers the upregulation of totipotency genes and reduces H3K4me3 modifications at glycolysis enzyme promoters, thereby suppressing glycolytic processes. Furthermore, we found that a reduction in AKT, a downstream target of Tcl1, is associated with activation of the 2C gene and consequent shifts in energy metabolism. Specifically, AKT inhibition leads to succinate accumulation, further highlighting the role of succinate in the cell fate transition. Our findings underscore the central role of Tcl1-AKT-succinate axis in regulating totipotency and pluripotency through coordinated energy metabolic pathways.

Hematopoiesis and the behavior of hematopoietic stem and progenitor cells (HSPCs) are regulated by the bone marrow niche. Here, we introduce the major niche cell types in bone marrow and their response to stress condition. We highlight the hematopoietic response and bone marrow niche adaptation to inflammatory condition and non-hematopoietic diseases, which are not systematically summarized. These emerging data suggest targeting hematopoiesis and bone marrow niche may provide novel therapeutic target to precisely control the progression of the diseases.

Human pluripotent stem cells (hPSCs) hold great promise in regenerative medicine. However, immune rejections remain one of the major obstacles to stem cell therapy. Though conventional immunosuppressants are available in clinics, the side effects prevent the wide application of hPSCs derivatives, compromising both survival rate and quality of life. In recent years, a myriad of strategies aimed at inducing immune tolerance specifically by engineering stem cells has been introduced to society. One strategy involves human leukocyte antigen (HLA) deletion through gene editing, affording allografts the capability to evade the host immune system. Another strategy involves immune cloak, which is the focus of this review, with emphasis on the overexpression of immune checkpoints and the blocking of immune cytotoxic pathways. Nevertheless, co-transplantation with mesenchymal stem cells (MSCs) and enhanced MSCs confers immune privilege to engraftments. This review summarizes recent studies on the intricacies of immune tolerance induction by engineering stem cells. In addition, we endeavor to deliberate upon the safety and limitations associated with this promising and potential therapeutic modality.