Biology subjects

Park, C.-H.

Publications and source records attributed to Park, C.-H..

5 recordsLinked to original sources

bioRxiv2026

Directed conversion of porcine extended pluripotent stem cells into trophoblast-like stem cells through modulation of conserved TGF-β and ERK signaling pathways

Trophoblast stem cells (TSCs) provide a tractable system for interrogating the signaling pathways that govern extraembryonic lineage commitment. Although trophoblast specification has been extensively characterized in humans and rodents, comparable tools and molecular frameworks remain poorly defined in pigs. Here, we identify defined biochemical conditions that enable the conversion of porcine extended pluripotent stem cells (pEPSCs) into TSCs. Pharmacological inhibition experiments demonstrate that coordinated repression of TGF-{beta}/Activin and MEK/ERK signaling is sufficient to induce and maintain a stable trophoblast transcriptional program. Under these conditions, cells robustly upregulate core trophoblast regulators, including CDX2, GATA3, KRT7/18, HAND1, and ELF5, while concomitantly suppressing pluripotency- and hypoblast-associated gene networks. Bulk transcriptomic profiling reveals extensive lineage reprogramming, with enrichment of pathways related to cell adhesion, extracellular matrix organization, and placental development. Functional in vivo assays further show that induced trophoblast-like cells form small, non-teratomatous lesions that express extraembryonic markers, whereas parental pEPSCs generate teratomas that contain derivatives of all three germ layers. Together, these findings establish that combined inhibition of TGF-{beta}/Activin and MEK/ERK signaling is sufficient to specify porcine trophoblast identity from pluripotent stem cells and provide a biochemical framework for dissecting conserved and species-specific mechanisms underlying trophoblast specification and placental development. HighlightsO_LIDefined signaling conditions enabling stable conversion of porcine extended pluripotent stem cells (EPSCs) into trophoblast-like stem cells (TSC). C_LIO_LIDual inhibition of TGF-{beta}/Activin and ERK pathways drives robust trophoblast commitment. C_LIO_LITranscriptional reprogramming reveals conserved trophectoderm regulatory networks distinct from pluripotency and hypoblast states. C_LIO_LIInduced porcine TSCs display restricted in vivo potential, consistent with trophoblast identity. C_LI

developmental biology↗

bioRxiv2025

A porcine germ cell depletion model to investigate the role of germ cells in gonadal development.

The molecular mechanisms regulating the germ cell and gonadal somatic cell development are complex and are still poorly understood in non-rodent mammals. The Nanos family gene-NANOS3 is expressed in the migrating primordial germ cells (PGC) and has key roles in germ cell survival in several species. Herein, we investigated the role of NANOS3 in pigs-an animal model of dual agricultural and biomedical importance. Consistent with prior reports, we found that disruption of NANOS3 expression did not affect PGC specification. Similarly, migration of PGC to the genital ridge occurs normally, but soon followed by an increase in apoptosis and a loss of undifferentiated state by embryonic (e) day 20. Although NANOS3-/- gonads initiate development as ovaries or testes, they displayed structural defects. This is especially pronounced in the ovaries after the sex determination period (e35). Notably, we identified defects in pregranulosa and theca cell development at a single-cell resolution, suggesting that germ cells are important for gonadal somatic cell development. This germ cell depletion model therefore offers novel insights into the potential role of germ cells in the emergence of gonadal somatic lineages.

developmental biology↗

bioRxiv2024

Cold-inducible GOT1 activates the malate-aspartate shuttle in brown adipose tissue to support fuel preference for fatty acids

Brown adipose tissue (BAT) simultaneously metabolizes fatty acids (FA) and glucose under cold stress but favors FA as the primary fuel for heat production. It remains unclear how BAT steer fuel preference toward FA over glucose. Here we show that the malate-aspartate shuttle (MAS) is activated by cold in BAT and plays a crucial role in promoting mitochondrial FA utilization. Mechanistically, cold stress selectively induces glutamic-oxaloacetic transaminase (GOT1), a key MAS enzyme, via the {beta}-adrenergic receptor-PKA-PGC-1 axis. The increase in GOT1 activates MAS, transferring reducing equivalents from the cytosol to mitochondria. This process enhances FA oxidation in mitochondria while limiting glucose oxidation. In contrast, loss of MAS activity by GOT1 deficiency reduces FA oxidation, leading to increased glucose oxidation. Together, our work uncovers a unique regulatory mechanism and role for MAS in mitochondrial fuel selection and advances our understanding of how BAT maintains fuel preference for FA under cold conditions. HighlightsO_LIGot1 is markedly induced by cold in BAT via a {beta}-adrenergic receptor-PKA-PGC-1 axis C_LIO_LIThe increase in cytosolic GOT1 activates the malate-aspartate shuttle (MAS) C_LIO_LIMAS activation promotes fatty acid oxidation while reducing glucose oxidation C_LIO_LILoss of MAS activity in BAT by Got1 deletion shifts the fuel preference to glucose C_LI

cell biology↗

bioRxiv2022

LTP-like noninvasive striatal brain stimulation enhances striatal activity and motor skill learning in humans

The stimulation of deep brain structures has thus far only been possible with invasive methods. Transcranial electrical temporal interference stimulation (tTIS) is a novel, noninvasive technology that might overcome this limitation. The initial proof-of-concept was obtained through modeling, physics experiments and rodent models. Here, we show for the first time successful noninvasive neuromodulation of the striatum via tTIS in humans using computational modeling, fMRI studies and behavioral evaluations. Theta-burst patterned striatal tTIS increased activity in the striatum and associated motor network. Furthermore, striatal tTIS enhanced motor performance, especially in healthy older participants as they have lower natural learning skills than younger subjects. These findings place tTIS as exciting new method to target deep brain structures in humans noninvasively, thus enhancing our understanding of their functional roles. Moreover, our results lay the groundwork for innovative, noninvasive treatment strategies for brain disorders in which deep striatal structures play key pathophysiological roles.

neuroscience↗

bioRxiv2018

An assessment of the interactions between climatic conditions and genetic characteristic on the agricultural performance of soybeans grown in Northeast Asia

Glycine max, commonly known as soybean or soya bean, is a species of legume native to East Asia. The interactions between climatic conditions and genetic characteristic affect the agricultural performance of soybean. Therefore, an investigation to identify the main elements affecting the agricultural performances of 11 soybeans was conducted in Northeast Asia, China [Harbin (45{degrees}12'N) Yanji (42{degrees}53'N) Dalian (39{degrees}30'N) Qingdao (36{degrees}26'N)] Republic of Korea [Suwon (37{degrees}16'N) and Jeonju (35{degrees}49'N)]. The days to flowering (DTF) of soybeans with the e1-nf and e1-as alleles and the E1e2e3e4 genotype, except Keumgangkong, Tawonkong, and Duyoukong, was relatively short compared to soybeans with other alleles. Although DTF of the soybeans was highly correlated to all climatic conditions, days to maturity (DTM) and 100-seed weight (HSW) of the soybeans showed no significant correlation with any climatic conditions. The soybeans with a dominant Dt1 allele, except Tawonkong, had the longest stem length (STL). Moreover, the STL of the soybeans grown at the test fields showed a positive correlation with only day length (DL) although the results of our chamber test showed that STL of soybean was positively affected by average temperature (AVT) and DL. Soybean yield (YLD) showed positive correlations with latitude and DL (except L62-667, OT89-5, and OT89-6) although the response of YLD to the climatic conditions was cultivar-specific. Our results show that DTF and STL of soybeans grown in Northeast Asia are highly affected by DL although AVT and genetic characteristic also affect DTF and STL. Along with these results, we confirmed that the DTM, HSW, and YLD of the soybeans vary in relation to their genetic characteristic.

plant biology↗