Xiaochen Fan

First Affiliated Hospital of Anhui Medical University

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Patrick Tam

Children's Medical Research Institute

Nicolas Fossat

Copenhagen University Hospital

Pierre Osteil

University of Sydney

Mark E. Graham

Children's Medical Research Institute

Jane Sun

University of Queensland

David A.F. Loebel

University of Sydney

Emilie Wilkie

UNSW Sydney

Zhen Chen

East China Normal University

Tri C. Nguyen

Aalto University

Sheng Zhong

Genemo (United States)

Cooperative Institutions

Stanford University

University of Sydney

Xi'an Jiaotong University

Children's Medical Research Institute

Cardiovascular Institute of the South

University of California, San Diego

La Jolla Bioengineering Institute

Xi'an Honghui Hospital

Palo Alto University

Chinese Academy of Medical Sciences & Peking Union Medical College

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The role and mechanisms of action of SIRT6 in the suppression of postoperative epidural scar formation

International Journal of Molecular Medicine (2016)

Xiaochen Fan Junjie Chen Da Shi Jing Jia Jia He

In order to investigate the role which sirtuin-6 (SIRT6) plays in lumbar spinal epidural fibrosis (EF) and scar formation in vitro and in vivo, SIRT6 and transforming growth factor β (TGF‑β) protein levels in the lumbar disc of patients were detected using western blotting in patients who had undergone a laminectomy. The results demonstrated that SIRT6 expression was significantly reduced in the lumbar discs of patients in whom an epidural scar had formed, but the expression pattern of TGF-β2 was much higher. Subsequently, a pcDNA‑SIRT6 expression vector was constructed and transfected into the primary fibroblasts isolated from the epidural scars. Flow cytometric and MTT analyses indicated that overexpression of SIRT6 suppressed the proliferation of the fibroblasts, and TGF‑β2 and interleukin-1α expression, as well as collagen type I (Col I) production. The results of bioinformatics and molecular biological analyses demonstarted that TGF‑β2 was a target of microRNA-21 (miR-21) and SIRT6 overexpression suppressed the levels of TGF-β2 through promoting the expression of miR-21. Finally, by injecting the pcDNA-SIRT6 vector, it was possible to observe that SIRT6 suppressed EF and epidural scar formation in vivo. In conclusion, we noted that SIRT6 suppressed EF and epidural scar formation in vitro and in vivo. It was also noted that SIRT6 overexpression suppressed TGF-β2 levels by promoting the expression of miR-21.

10.3892/ijmm.2016.2522

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Natural display of nuclear-encoded RNA on the cell surface and its impact on cell interaction

Genome biology (2020)

Norman Huang Xiaochen Fan Kathia Zaleta-Rivera Tri C. Nguyen Jiarong Zhou

Abstract Background Compared to proteins, glycans, and lipids, much less is known about RNAs on the cell surface. We develop a series of technologies to test for any nuclear-encoded RNAs that are stably attached to the cell surface and exposed to the extracellular space, hereafter called membrane-associated extracellular RNAs (maxRNAs). Results We develop a technique called Surface-seq to selectively sequence maxRNAs and validate two Surface-seq identified maxRNAs by RNA fluorescence in situ hybridization. To test for cell-type specificity of maxRNA, we use antisense oligos to hybridize to single-stranded transcripts exposed on the surface of human peripheral blood mononuclear cells (PBMCs). Combining this strategy with imaging flow cytometry, single-cell RNA sequencing, and maxRNA sequencing, we identify monocytes as the major type of maxRNA+ PBMCs and prioritize 11 candidate maxRNAs for functional tests. Extracellular application of antisense oligos of FNDC3B and CTSS transcripts inhibits monocyte adhesion to vascular endothelial cells. Conclusions Collectively, these data highlight maxRNAs as functional components of the cell surface, suggesting an expanded role for RNA in cell-cell and cell-environment interactions.

Cell type

10.1186/s13059-020-02145-6

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Citations (38)

Endocardium-to-coronary artery differentiation during heart development and regeneration involves sequential roles of Bmp2 and Cxcl12/Cxcr4

Developmental Cell (2022)

Gaetano D’Amato Ragini Phansalkar Jeffrey A. Naftaly Xiaochen Fan Zhainib Adel Amir

Endocardium

Heart development

10.1016/j.devcel.2022.10.007

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Citations (27)

Pumping ions

Clinical and Experimental Pharmacology and Physiology (2011)

Ronald J. Clarke Xiaochen Fan

1. This is a concise review of the field of ion pumping from the perspective of the authors. 2. The period covered spans the discovery of Na(+) and K(+) concentration gradients across animal cell membranes by Carl Schmidt in the 1850s, through the isolation of the Na(+) /K(+) -ATPase by Skou in 1957 (for which he was awarded the 1997 Nobel Prize in Chemistry), to the publication of the first crystal structure of the enzyme in 2007 and beyond. 3. Contributions of the authors' research group to the resolution of the questions of the mechanism of the allosteric role of ATP within the Na(+) /K(+) -ATPase reaction cycle and how protomeric versus diprotomeric states of the enzyme influence its kinetics are discussed within the context of the research field. 4. The results obtained indicate that the Na(+) /K(+) -ATPase has a single ATP binding site, which can be catalytic or allosteric in different parts of the enzyme's reaction cycle. 5. The long-running controversy over whether P-type ATPases function as protomers or diprotomers can be resolved in the case of the Na(+) /K(+) -ATPase by an ATP-induced dissociation of (αβ)(2) diprotomers into separate αβ protomers. 6. Kinetic data suggest that protein-protein interactions between the two αβ protomers within an (αβ)(2) diprotomer result in a much lower enzymatic turnover (i.e. a lower gear) when only one of the α-subunits of the diprotomer has bound ATP. The inactive αβ protomer within the diprotomer can be thought of as causing a drag on the active protomer.

Catalytic cycle

10.1111/j.1440-1681.2011.05590.x

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Citations (23)

Is the likelihood of dysphagia different in patients undergoing one-level versus two-level anterior cervical discectomy and fusion?

The Spine Journal (2020)

Xiaochen Fan Baohui Wang

10.1016/j.spinee.2020.04.003

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Citations (2)

TWIST1 homo- and heterodimers orchestrate specificity control in embryonic stem cell lineage differentiation and craniofacial development

Research at the University of Copenhagen (University of Copenhagen) (2019)

Xiaochen Fan Ashley J. Waardenberg Madeleine Demuth Pierre Osteil Jane Sun

Abstract Combinations of bHLH factors dimers generate great functional diversity required for cell type specification in development. The bHLH factor TWIST1 plays pleiotropic roles in craniofacial development. However, which combination of TWIST1 dimers are involved in craniofacial development, and what impact each dimer impose on gene regulation network remained elusive. Proteome profiling of human-TWIST1 expressing cell lines and transcriptome analysis of mouse cranial mesenchyme revealed TWIST1 homodimer and heterodimers with TCF3, TCF4 and TCF12 E-proteins as preferred combinations. We found that balance of homo- and heterodimers were impaired by human disease mutations in TWIST1 Helix domains, which may underpin the developmental defects in haploinsufficiency. Further, loss or gain of function analysis of TWIST1-E-protein dimers in differentiating embryonic stem cells revealed their previously unappreciated roles in lineage specification. TWIST1-E-protein heterodimers activate mesoderm and neural crest differentiation through epithelial-to-mesenchymal transition, whilst TWIST1 homodimers maintained a progenitor-like state and blocked entry to endoderm lineages.

Twist transcription factor

Haploinsufficiency

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Application study on catheterization to pseudoaneurysm of membranous ventricular septal defect with patent ductus arteriosus occlusion devices in children

Chinese Journal of Postgraduates of Medicine (2011)

Xiang Yun Pengfei Du Yang Shan-zhi Xiaochen Fan Cheng Zi-ping

Ductus arteriosus

Cardiac catheterization

Pseudoaneurysm

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Stress-induced RNA–chromatin interactions promote endothelial dysfunction

Nature Communications (2020)

Riccardo Calandrelli Lixia Xu Yingjun Luo Weixin Wu Xiaochen Fan

Abstract Chromatin-associated RNA (caRNA) has been proposed as a type of epigenomic modifier. Here, we test whether environmental stress can induce cellular dysfunction through modulating RNA-chromatin interactions. We induce endothelial cell (EC) dysfunction with high glucose and TNFα (H + T), that mimic the common stress in diabetes mellitus. We characterize the H + T-induced changes in gene expression by single cell (sc)RNA-seq, DNA interactions by Hi-C, and RNA-chromatin interactions by iMARGI. H + T induce inter-chromosomal RNA-chromatin interactions, particularly among the super enhancers. To test the causal relationship between H + T-induced RNA-chromatin interactions and the expression of EC dysfunction-related genes, we suppress the LINC00607 RNA. This suppression attenuates the expression of SERPINE1 , a critical pro-inflammatory and pro-fibrotic gene. Furthermore, the changes of the co-expression gene network between diabetic and healthy donor-derived ECs corroborate the H + T-induced RNA-chromatin interactions. Taken together, caRNA-mediated dysregulation of gene expression modulates EC dysfunction, a crucial mechanism underlying numerous diseases.

10.1038/s41467-020-18957-w

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Citations (52)

Protein with tau-like repeats regulates neuronal integrity and lifespan inC. elegans

Journal of Cell Science (2013)

Yee Lian Chew Xiaochen Fan Jürgen Götz Hannah R. Nicholas

Protein with tau-like repeats (PTL-1) is the sole Caenorhabditis elegans homolog of tau and MAP2, which are members of the mammalian family of microtubule-associated proteins (MAPs). In mammalian neurons, tau and MAP2 are segregated, with tau being mainly localised to the axon and MAP2 mainly to the dendrite. In particular, tau plays a crucial role in pathology, as elevated levels lead to the formation of tau aggregates in many neurodegenerative conditions including Alzheimer's disease. We used PTL-1 in C. elegans to model the biological functions of a tau-like protein without the complication of functional redundancy which is observed among the mammalian MAPs. Our findings indicate that PTL-1 is important for the maintenance of neuronal health as animals age, as well as in the regulation of whole organism lifespan. In addition, gene dosage of PTL-1 is critical, as variations from wild-type levels are detrimental. We also observed that human tau is unable to robustly compensate for loss of PTL-1, although phenotypes observed in tau transgenic worms are dependent on the presence of endogenous PTL-1. Our data suggest that some of the effects of tau pathology may result from the loss of physiological tau function, and not solely from a toxic gain-of-function due to accumulation of tau.

Tau protein

Microtubule-associated protein

Loss function

10.1242/jcs.jcs124404

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Citations (55)

Cajan leaf combined with bone marrow-derived mesenchymal stem cells for the treatment of osteonecrosis of the femoral head

Experimental and Therapeutic Medicine (2014)

Da Shi Yindi Sun Jichao Yin Xiaochen Fan Honghao Duan

The aim of the present study was to observe the curative effect of traditional Chinese cajan leaves, combined with administration of bone marrow‑derived mesenchymal stem cells (BMSCs), on osteonecrosis of the femoral head (ONFH) in rats and to investigate the underlying mechanisms. A total of 40 rat ONFH models were established through liquid nitrogen freezing and were subsequently divided into groups: A, control; B, treated with cajan leaf; C, treated with BMSCs and D, treated with cajan leaf combined with BMSCs. Samples were obtained 30 days following treatment, and immunohistochemical staining of vascular endothelial growth factor (VEGF) and image analysis were performed. Chondrocytes and vascular endothelial cells were stained as a result of immunohistochemical staining and group D exhibited markedly deeper staining, and a significantly larger number of stained cells, compared with group A. Thus, in the present study, cajan leaf combined with BMSCs was shown to promote VEGF expression and improve ONFH repair.

10.3892/etm.2014.1622

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Citations (5)