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Sun, Y.-M.

Publications and source records attributed to Sun, Y.-M..

3 recordsLinked to original sources

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↗

High-resolution diploid 3D genome reconstruction using Pore-C data

In diploid organisms, spatial variations between homologous chromosomes are essential to many biological phenomena. Currently, it is still challenging to efficiently reconstruct a high-quality diploid 3D human genome. Here, we introduce Dip3D, reconstructing the diploid 3D human genome using Pore-C data of one sample. Dip3D has solved multiple problems in genome-wide SNV calling and haplo-tagging caused by the high sequencing error rates in Pore-C type data. Dip3D capitalizes on the high-order chromosomal interaction characteristics, enabling robust haplotype imputation and intricate haplotype-specific 3D structure discovery. Dip3D outperforms previous methods in data utilization rate, contact matrix resolution, and completeness by one order of magnitude. Moreover, Dip3D allows capturing haplotype high-order interactions that are unseen in Hi-C type data. We demonstrated the identified haplotype substructures such as Topologically Associating Domains (TADs) in the constructed 3D human genome, and unraveled connections between genic haplotype-specific high-order interactions and imbalanced allelic expression.

genomics↗

Nuclear export of chimeric mRNAs depends on an lncRNA-triggered autoregulatory loop

Aberrant chromosomal translocations leading to tumorigenesis have been ascribed to the heterogeneously oncogenic functions. However, how fusion transcripts exporting remains to be declared. Here, we showed that the nuclear speckle-specific long non coding RNA MALAT1 controls chimeric mRNA export processes and regulates myeloid progenitor cell differentiation in malignant hematopoiesis. We demonstrated that MALAT1 regulates chimeric mRNAs export in an m6A-dependent manner and thus controls hematopoietic cell differentiation. Specifically, reducing MALAT1 or m6A methyltransferases and the reader YTHDC1 result in the universal retention of distinct oncogenic gene mRNAs in nucleus. Mechanically, MALAT1 hijacks both the chimeric mRNAs and fusion proteins in nuclear speckles during chromosomal translocations and mediates the colocalization of oncogenic fusion proteins with METTL14. MALAT1 and fusion protein complexes serve as a functional loading bridge for the interaction of chimeric mRNA and METTL14. This study demonstrated a universal mechanism of chimeric mRNA transport that involves lncRNA-fusion protein-m6A autoregulatory loop for controlling myeloid cell differentiation. Targeting the lncRNA-triggered autoregulatory loop to disrupt chimeric mRNA transport might represent a new common paradigm for treating blood malignancies.

cancer biology↗