Biology subjects

Li, C.-J.

Publications and source records attributed to Li, C.-J..

5 recordsLinked to original sources

bioRxiv2024

Ternary representation of contextual information along the CA1 transverse axis

Episodic memory refers to the recollection of personally experienced events anchored in spatial contexts. Salient objects within a navigation environment serve as both landmarks and event cues; however, the nuanced integration of these elements during episodic memory formation is not well understood. The mnemonic functions of the hippocampal CA1 region are partially organized along its transverse axis, with proximal and distal subregions preferentially processing spatial and non-spatial information, respectively. Based on comprehensive analysis of neuronal responses along the CA1 proximodistal axis to manipulations of environmental cues and object features, we identified an event-like population coding within CA1 following object displacement. In addition, the neuronal responses at both initial and relocated object locations were shaped by distinct convergent inputs. These findings highlight the specific roles that objects may play in spatial navigation and memory encoding, providing novel insights into the selective processing of object-related information within the entorhinal-hippocampal network. Significance StatementSalient objects within a navigation environment serve as both landmarks and event cues critical for episodic memory. However, the enigmatic contribution of objects to the "where" and "what" components of episodic memory remains poorly understood. Here we comprehensively analyzed the neuronal responses in the hippocampal CA1 region along its transverse axis, to manipulations of environmental cues and object features. Our results revealed an event-like population coding within CA1 following object displacement, suggesting a minimal landmark role these objects play during memory formation. This study provides novel insights into the selective and flexible processing of object-related information within the entorhinal-hippocampal network.

neuroscience↗

bioRxiv2023

A comparison of behavior paradigms assessing spatial memory in tree shrew

Spatial cognition enables animals to navigate the environment. Impairments in spatial navigation are often preclinical signs of Alzheimers disease (AD) in human. Therefore, evaluating spatial memory deficits is valuable when assessing incipient AD in animal models. The Chinese tree shrew, a close relative of primates, possesses many features that make it suitable for AD research. However, there is a scarcity of reliable behavior paradigms to monitor changes in spatial cognition in this species. To address this, we established reward-based paradigms in the radial-arm maze and the cheeseboard maze for tree shrew, and tested spatial memory of a group of twelve male animals in both tasks, along with a control water maze test, before and after bilateral lesions to the hippocampus, the brain region essential for spatial navigation. Tree shrews memorized target positions during training, and their task performance improved gradually until reaching a plateau in all three mazes. After the lesion, spatial learning was compromised in both newly-developed tasks, whereas memory retrieval was impaired in the water maze. Furthermore, individual task performance in both dry-land paradigms depended heavily on the size of remaining hippocampal tissue. Notably, all lesioned animals displayed spatial memory deficits in the cheeseboard task, but not in the other two paradigms. Our results suggest that the cheeseboard task currently represents the most sensitive paradigm for assessing spatial memory in tree shrew, with the potential to monitor progressive cognitive declines in aged or genetically modified animals developing AD-like symptoms. Significance StatementCognitive tests that monitor impairments in spatial memory play a crucial role in evaluating animal models with early-stage Alzheimers disease (AD). The Chinese tree shrew possesses many features suitable for an AD model, yet behavior tests assessing spatial cognition in this species are lacking. Here we developed novel behavior paradigms tailored to measure spatial memory in tree shrews and evaluated their sensitivity to changes in spatial learning by examining a group of hippocampus-lesioned animals. Our results indicate that the cheeseboard task effectively detects impairments in spatial memory and holds potential for monitoring the progressive cognitive decline in aged or genetically modified tree shrews that develop AD-like symptoms. This research may facilitate the use of tree shrew model in AD research.

animal behavior and cognition↗

bioRxiv2022

Orchestration of alternative splicing regulates bone marrow mesenchymal stem cells fate during aging

Senescence and change of differentiation direction in bone marrow stromal cells (BMSCs) are two of the most important causes of age-related bone loss. As an important post-transcriptional regulatory pathway, alternative splicing (AS) regulates diversity of gene expression. However, the role of AS in BMSCs during aging remains poorly defined. Here we identify AS in specific genes disrupt gene expression pattern and result in age-related debility of BMSCs. We demonstrate the deficiency of splicing factor Y-box protein 1 (YBX1) result in mis-splicing in genes such as Fn1, Taz, Sirt2 and Sp7, further contributing to senescence and shift in differentiation direction of BMSCs during aging. Deletion or over-expression of YBX1 in BMSCs accelerate bone loss or stimulate bone formation in mice. Notably, we identify a small compound sciadopitysin which attenuate the degradation of YBX1 and attenuate bone loss in old mice. Our study demonstrates elaborately controlled RNA splicing governs cell fate of BMSCs and provides a potential therapeutic target for age-related osteoporosis. SummaryThis study demonstrates that YBX1 deficiency induces pre-mRNA mis-splicing and causes senescence and shift in differentiation direction of BMSCs and further accelerates aging-related bone loss. This study identifies Sciadopitysin could reverse this process by targeting YBX1.

cell biology↗

bioRxiv2022

Sequential functional differentiation of luminal epithelial cells regulated by maternal and embryonic signaling in the mouse endometrium

Embryo implantation requires temporospatial maternal-embryo dialog to regulate the interactions between an activated blastocyst and a receptive endometrium; however, the details of the related cell-specific coordination is largely unknown because of the cellular complexity and dynamic developmental processes of both the embryo and endometrium during peri-implantation. By comparing single-cell RNA (scRNA) data obtained from entire uteri of pregnant and pseudo-pregnant mice with embryos that were in the oviduct (dpc2.5 days post-coitum [dpc]) or had entered the uterus (after 3.5 dpc), we found a maternal estrogen and progesterone signaling-dependent functional differentiation process in which progesterone induced estrogen-responsive luminal epithelial cells to differentiate into two new types of epithelial cells: adhesion epithelial cells (AECs) and supporting epithelial cells (SECs) on 2.5 dpc. In addition to maternal signaling data, the uterine scRNA and corresponding embryo bulk sequencing data were obtained, and analyses revealed that embryonic Pdgfa and Efna3/4 signaling activated AECs and SECs, enhancing the attachment of embryos to the endometrium after implantation. Specifically, embryonic signaling induced additional transformation of AECs by preventing adjacent AECs, but not AECs away from the embryo in the implantation chamber, from undergoing apoptosis. Furthermore, we demonstrated that epithelial cell differentiation and related regulatory signaling were largely conserved in humans and mice. In the human endometrium, developmental defects of SOX9-positive epithelial cells similar to luminal epithelial cells were related to thin endometrium. Our work provides comprehensive and systematic information on endometrial luminal epithelial cell development directed by maternal and embryonic signaling, which is important for endometrial receptivity and embryo implantation.

cell biology↗

bioRxiv2020

Inactivation of LCN2/EGR1 Promotes Oligodendrocyte Progenitor Cell Differentiation and Remyelination after White Matter Injury

The insufficient remyelination due to the impaired oligodendrocyte precursor cell differentiation and maturation is highly associated with irreversible white matter injury and neurological deficits. Consequently, inhibitory components and microenvironment for remyelination might serve as potential therapeutic targets for treating white matter injury after acute central nervous system injury and neurodegeneration diseases. Lipocalin-2 was recently reported to corelate with white matter in both atypical, acute white matter injured disease subarachnoid hemorrhage and typical, chronic white matter injured disease multiple sclerosis. To elucidate the role and underlying mechanism of Lipocalin-2 in oligodendrocyte precursor cell differentiation and remyelination, we used genetic inhibition and a constitutive conditional knockout model with subarachnoid hemorrhage or multiple sclerosis. We found that the genetic inhibition of the increase in Lipocalin-2 promoted oligodendrocyte precursor cell differentiation, remyelination, and functional recovery after subarachnoid hemorrhage or multiple sclerosis. Unexpectedly, the inhibition of Lipocalin-2 did not reduce glial activation and inflammation. Lipocalin-2 was shown to activate Early Growth Response Protein 1 in oligodendrocyte precursor cells, which is partly regulated by its receptor SLC22A17. In the conditional knockout of Early Growth Response Protein 1 in oligodendrocyte precursor cells, we discovered enhanced oligodendrocyte precursor cell differentiation in developing and injured white matter; consistently, the specific inactivation of Early Growth Response Protein 1 promoted remyelination and neurological recovery after subarachnoid hemorrhage or multiple sclerosis. Thus, we propose that following white matter injury in humans, the increase in Lipocalin-2 activates Early Growth Response Protein 1 and consequently impair oligodendrocyte precursor cell differentiation and myelin repair. Our results suggest that therapies specifically inactivating Lipocalin-2/ Early Growth Response Protein 1 signal in oligodendroglial lineage cells could represent a novel strategy to enhance differentiation and remyelination in white matter injury patients.

neuroscience↗