Biology subjects

Yokomizo, R.

Publications and source records attributed to Yokomizo, R..

4 recordsLinked to original sources

bioRxiv2024

Generation of spermatogonia from pluripotent stem cells in humans and non-human primates

Failures in germline development drive male infertility, but the lack of model systems that recapitulate human spermatogenesis hampers therapeutic development. Here, we have developed a system to differentiate human induced pluripotent stem cells (iPSCs) into primordial germ cell-like cells that self-organize within xenogeneic reconstituted testes (xrTestes) generated from mouse fetal testicular cells. Subsequent transplant of xrTestes into immunodeficient mice resulted in efficient generation of undifferentiated and differentiated spermatogonia as well as preleptotene spermatocytes with striking similarities to their in vivo counterparts. As future clinical application will require testing in non-human primates, we utilized a similar strategy to differentiate rhesus iPSCs through all fetal germ cell stages into spermatogonia-like cells. Together, these models will serve as steppingstone to completion of human male in vitro gametogenesis.

developmental biology↗

bioRxiv2024

Defining the cellular origin of seminoma by transcriptional and epigenetic mapping to the normal human germline

Aberrant male germline development can lead to the formation of seminoma, a testicular germ cell tumor. Seminomas are biologically similar to primordial germ cells (PGCs) and many bear an isochromosome 12p [i(12p)] with two additional copies of the short arm of chromosome 12. By mapping seminoma transcriptomes and open chromatin landscape onto a normal human male germline trajectory, we find that seminoma resembles premigratory/migratory primordial germ cells, but exhibit enhanced germline and pluripotency programs, and upregulation of genes involved in apoptosis, angiogenesis, and MAPK/ERK pathways. Using pluripotent stem cell-derived PGCs from Pallister Killian syndrome patients mosaic for i(12p) to model seminoma, we identify gene dosage effects that may contribute to transformation. As murine seminoma models do not exist, our analyses provide critical insights into genetic, cellular and signaling programs driving seminoma transformation, and the newly developed in vitro platform permits evaluation of additional signals required for seminoma tumorigenesis.

developmental biology↗

bioRxiv2023

Functional and long-lived melanocytes from human pluripotent stem cells with transient ectopic expression of JMJD3

BackgroundMelanocytes are an essential part of the epidermis, and their regeneration has received much attention because propagation of human adult melanocytes in vitro is too slow for clinical use. Differentiation from human pluripotent stem cells to melanocytes has been reported, but the protocols to produce them require multiple and complex differentiation steps. MethodWe differentiated human embryonic stem cells (hESCs) that transiently express JMJD3 to pigmented cells. We investigated whether the pigmented cells have melanocytic characteristics and functions by qRT-PCR, immunocytochemical analysis and flow cytometry. We also investigated their biocompatibility by injecting the cells into immunodeficient mice for clinical use. ResultWe successfully differentiated and established a pure culture of melanocytes. The melanocytes maintained their growth rate for a long time, approximately 200 days, and were functional. They exhibited melanogenesis and transfer of melanin to peripheral keratinocytes. Moreover, melanocytes simulated the developmental processes from melanoblasts to melanocytes. The melanocytes had high engraftability and biocompatibility in the immunodeficient mice. ConclusionThe robust generation of functional and long-lived melanocytes are key to developing clinical applications for the treatment of pigmentary skin disorders.

cell biology↗

bioRxiv2022

Novel therapeutic strategies for injured endometrium: Autologous intrauterine transplantation of menstrual blood-derived cells from infertile patients

BackgroundMenstrual blood-derived cells show regenerative potential as a mesenchymal stem cell and may therefore be a novel stem cell source of treatment for refractory infertility with injured endometrium. However, there have been few pre-clinical studies using cells from infertile patients, which needs to be addressed before establishing an autologous transplantation. Herein, we aimed to investigate the therapeutic capacity of menstrual blood-derived cells from infertile patients on endometrial infertility. MethodsWe collected menstrual blood-derived cells from volunteers and infertile patients, and confirmed their mesenchymal stem cell phenotype by flowcytometry and induction of tri-lineage differentiation. We compared the proliferative and paracrine capacities of these cells. Furthermore, we also investigated the regenerative potential and safety concerns of the intrauterine transplantation of infertile patient-derived cells using a mouse model with mechanically injured endometrium. ResultsMenstrual blood-derived cells from both infertile patients and volunteers showed phenotypic characteristics of mesenchymal stem cells. In vitro proliferative and paracrine capacities for wound healing and angiogenesis were equal for both samples. Furthermore, the transplantation of infertile patient-derived cells into uterine horns of the mouse model ameliorated endometrial thickness, prevented fibrosis and improved fertility outcomes without any apparent complications. ConclusionsIn our preclinical study, intrauterine transplantation of menstrual blood-derived cells may be a novel and attractive stem cell source for the curative and prophylactic therapy for injured endometrium. Further studies will be warranted for future clinical application.

cell biology↗