Biology subjects

Kawagoe, S.

Publications and source records attributed to Kawagoe, S..

3 recordsLinked to original sources

bioRxiv2024

Generation of human-pig chimeric renal organoids using iPSC technology

The potential of using porcine organs and human induced pluripotent stem cell (iPSC)-derived organoids as alternative organs for human transplantation has garnered growing attention. However, both approaches still face technological challenges. Interspecies chimeric organ production using human iPSCs is expected to be another promising approach that addresses the challenges associated with organ production. Our research group successfully generated human-mouse chimeric renal organoids by utilizing human iPSC-derived nephron progenitor cells (NPCs) and fetal mouse kidneys. However, the current technology has limited engraftment and development capabilities for human NPCs, and there have been no reports of generating interspecies chimeric renal organoids in larger animals, limited only to rodents. Therefore, in this study, we embarked on the production of human-pig chimeric renal organoids using the pig kidney, which is considered the most promising source of organs for interspecies transplantation to humans. To construct a human-pig chimeric renal organoid culture system, we first modified the existing human-mouse chimeric renal organoid culture system and developed a method that enables the survival and continued renal development of both species. This method was found to be applicable to porcine fetal kidney cells, and ultimately, we successfully produced human-pig chimeric renal organoids. Furthermore, this culture method can also be applied to the generation of human interspecies chimeric kidneys for future clinical applications. The findings of this study serve as a foundational technology that will greatly accelerate future research in humanized pig kidney production for clinical purposes, and are also expected to be used as an evaluation technique to ensure the quality of human NPCs for xenotransplantation.

bioengineering↗

bioRxiv2023

Atypical heat shock transcription factor HSF5 is critical for male meiotic prophase under non-stress conditions

Meiotic prophase progression is differently regulated in males and females. In males, pachytene transition during meiotic prophase is accompanied by robust alteration in gene expression. However, how gene expression is regulated differently to ensure meiotic prophase completion in males remains elusive. Herein, we identified HSF5 as a male germ cell-specific heat shock transcription factor (HSF) for meiotic prophase progression. Genetic analyses and single-cell RNA-sequencing demonstrated that HSF5 is essential for progression beyond the pachytene stage under non-stress conditions rather than heat stress. Chromatin binding analysis in vivo and DNA-binding assays in vitro suggested that HSF5 binds to promoters in a subset of genes associated with chromatin organization. HSF5 recognizes a DNA motif different from typical heat shock elements recognized by other canonical HSFs. This study suggests that HSF5 is an atypical HSF that enforces the gene expression program for pachytene transition during meiotic prophase in males.

developmental biology↗

bioRxiv2021

Oxidative phase transition of heat shock factor-1

Heat shock factor 1 (Hsf1) was found as a central upregulator of molecular chaperones in stress adaptation, but it has recently been rediscovered as a major component of persistent nuclear stress bodies (nSBs). When the persistently stressed cells undergo apoptosis, the phase transition of nSBs from fluid to gel-like states is proposed to be an important event in switching the cell fate from survival to death. Nonetheless, how the phase separation and transition of nSBs are driven remain unanswered. In this study, we discovered that Hsf1 formed liquid-liquid phase separation droplets in vitro, causing the assembly of Hsf1 to drive nSBs formation. Under oxidative conditions, disulfide-bonded and oligomerized Hsf1 formed gel-like and more condensed droplets, confirmed through fluorescence recovery, refractive index imaging, and light scattering. Then, on the basis of our results, we proposed that Hsf1 undergoes oxidative phase transition by sensing redox conditions potentially to drive the cell fate decision by nSBs.

biochemistry↗