Stanford Advisors

All Publications

  • GSEApy: a comprehensive package for performing gene set enrichment analysis in Python. Bioinformatics (Oxford, England) Fang, Z., Liu, X., Peltz, G. 2022


    Gene Set enrichment analysis (GSEA) is a commonly used algorithm for characterizing gene expression changes. However, the currently available tools used to perform GSEA have a limited ability to analyze large datasets, which is particularly problematic for the analysis of single-cell data. To overcome this limitation, we developed a GSEA package in Python (GSEApy), which could efficiently analyze large single-cell datasets.We present a package (GSEApy) that performs GSEA in either the command line or Python environment. GSEApy uses a Rust implementation to enable it to calculate the same enrichment statistic as GSEA for a collection of pathways. The Rust implementation of GSEApy is 3-fold faster than the Numpy version of GSEApy (v0.10.8) and uses >4-fold less memory. GSEApy also provides an interface between Python and Enrichr web services, as well as for BioMart. The Enrichr API enables GSEApy to perform over-representation analysis for an input gene list. Furthermore, GSEApy consists of several tools, each designed to facilitate a particular type of enrichment analysis.The new GSEApy with Rust extension is deposited in PyPI: The GSEApy source code is freely available at Also, the documentation website is available at available online.

    View details for DOI 10.1093/bioinformatics/btac757

    View details for PubMedID 36426870

  • SOX1 Is Required for the Specification of Rostral Hindbrain Neural Progenitor Cells from Human Embryonic Stem Cells ISCIENCE Liu, X., Fang, Z., Wen, J., Tang, F., Liao, B., Jing, N., Lai, D., Jin, Y. 2020; 23 (9): 101475


    Region-specific neural progenitor cells (NPCs) can be generated from human embryonic stem cells (hESCs) by modulating signaling pathways. However, how intrinsic transcriptional factors contribute to the neural regionalization is not well characterized. Here, we generate region-specific NPCs from hESCs and find that SOX1 is highly expressed in NPCs with the rostral hindbrain identity. Moreover, we find that OTX2 inhibits SOX1 expression, displaying exclusive expression between the two factors. Furthermore, SOX1 knockout (KO) leads to the upregulation of midbrain genes and downregulation of rostral hindbrain genes, indicating that SOX1 is required for specification of rostral hindbrain NPCs. Our SOX1 chromatin immunoprecipitation sequencing analysis reveals that SOX1 binds to the distal region of GBX2 to activate its expression. Overexpression of GBX2 largely abrogates SOX1-KO-induced aberrant gene expression. Taken together, this study uncovers previously unappreciated role of SOX1 in early neural regionalization and provides new information for the precise control of the OTX2/GBX2 interface.

    View details for DOI 10.1016/j.isci.2020.101475

    View details for Web of Science ID 000577096400002

    View details for PubMedID 32905879

    View details for PubMedCentralID PMC7486433

  • SOX21 Ensures Rostral Forebrain Identity by Suppression of WNT8B during Neural Regionalization of Human Embryonic Stem Cells STEM CELL REPORTS Fang, Z., Liu, X., Wen, J., Tang, F., Zhou, Y., Jing, N., Jin, Y. 2019; 13 (6): 1038-1052


    The generation of brain region-specific progenitors from human embryonic stem cells (hESCs) is critical for their application. However, transcriptional regulation of neural regionalization in humans is poorly understood. Here, we applied a rostrocaudal patterning system from hESCs to dissect global transcriptional networks controlling early neural regionalization. We found that SOX21 is required for rostral forebrain fate specification. SOX21 knockout led to activation of Wnt signaling, resulting in caudalization of regional identity of rostral forebrain neural progenitor cells. Moreover, we identified WNT8B as a SOX21 direct target. Deletion of WNT8B or inhibition of Wnt signaling in SOX21 knockout neural progenitor cells restored rostral forebrain identity. Furthermore, SOX21 interacted with β-catenin, interfering with the binding of TCF4/β-catenin complex to the WNT8B enhancer. Collectively, these results unveil the unknown role of SOX21 and shed light on how a transcriptional factor modulates early neural regionalization through crosstalk with a key component of Wnt signaling.

    View details for DOI 10.1016/j.stemcr.2019.10.013

    View details for Web of Science ID 000502098700008

    View details for PubMedID 31761677

    View details for PubMedCentralID PMC6915843

  • CDK11 safeguards the identity of human embryonic stem cells via fine-tuning signaling pathways JOURNAL OF CELLULAR PHYSIOLOGY Ding, J., Fang, Z., Liu, X., Zhu, Z., Wen, C., Wang, H., Gu, J., Li, Q., Zeng, R., Li, H., Jin, Y. 2020; 235 (5): 4279-4290


    Signaling pathways transmit extracellular cues into cells and regulate transcriptome and epigenome to maintain or change the cell identity. Protein kinases and phosphatases are critical for signaling transduction and regulation. Here, we report that CDK11, a member of the CDK family, is required for the maintenance of human embryonic stem cell (hESC) self-renewal. Our results show that, among the three main isoforms of CDK11, CDK11p46 is the main isoform safeguarding the hESC identity. Mechanistically, CDK11 constrains two important mitogen-activated protein kinase (MAPK) signaling pathways (JNK and p38 signaling) through modulating the activity of protein phosphatase 1. Furthermore, CDK11 knockdown activates transforming growth factor β (TGF-β)/SMAD2/3 signaling and upregulates certain nonneural differentiation-associated genes. Taken together, this study uncovers a kinase required for hESC self-renewal through fine-tuning MAPK and TGF-β signaling at appropriate levels. The kinase-phosphatase axis reported here may shed new light on the molecular mechanism sustaining the identity of hESCs.

    View details for DOI 10.1002/jcp.29305

    View details for Web of Science ID 000489904800001

    View details for PubMedID 31612516

  • The chromatin remodeler Chd4 maintains embryonic stem cell identity by controlling pluripotency- and differentiation-associated genes JOURNAL OF BIOLOGICAL CHEMISTRY Zhao, H., Han, Z., Liu, X., Gu, J., Tang, F., Wei, G., Jin, Y. 2017; 292 (20): 8507-8519


    The unique properties of embryonic stem cells (ESCs), including unlimited self-renewal and pluripotent differentiation potential, are sustained by integrated genetic and epigenetic networks composed of transcriptional factors and epigenetic modulators. However, the molecular mechanisms underlying the function of these regulators are not fully elucidated. Chromodomain helicase DNA-binding protein 4 (Chd4), an ATPase subunit of the nucleosome remodeling and deacetylase (NuRD) complex, is highly expressed in ESCs. However, its function in ESC regulation remains elusive. Here we report that Chd4 is required for the maintenance of ESC self-renewal. RNAi-mediated silencing of Chd4 disrupted self-renewal and up-regulated lineage commitment-associated genes under self-renewal culture conditions. During ESC differentiation in embryoid body formation, we observed significantly stronger induction of differentiation-associated genes in Chd4-deficient cells. The phenotype was different from that caused by the deletion of Mbd3, another subunit of the NuRD complex. Transcriptomic analyses revealed that Chd4 secured ESC identity by controlling the expression of subsets of pluripotency- and differentiation-associated genes. Importantly, Chd4 repressed the transcription of T box protein 3 (Tbx3), a transcription factor with important functions in ESC fate determination. Tbx3 knockdown partially rescued aberrant activation of differentiation-associated genes, especially of endoderm-associated genes, induced by Chd4 depletion. Moreover, we identified an interaction of Chd4 with the histone variant H2A.Z. This variant stabilized Chd4 by inhibiting Chd4 protein degradation through the ubiquitin-proteasome pathway. Collectively, this study identifies the Chd4-Tbx3 axis in controlling ESC fate and a role of H2A.Z in maintaining the stability of Chd4 proteins.

    View details for DOI 10.1074/jbc.M116.770248

    View details for Web of Science ID 000401788600033

    View details for PubMedID 28298436

    View details for PubMedCentralID PMC5437254