Tianxiao (TX) Han is a Ph.D. candidate in the Biological and Biomedical Sciences (BBS) Program and the Therapeutics Graduate Program (TGP). TX is interest in stem cell biology and regenerative medicine. His thesis project focuses on the transcriptional and epigenetic regulatory mechanisms that orchestrate hematopoietic stem cell niche microenvironment, which may help us better understand hematologic function and develop therapies targeting blood disorders.

Recent Publications

Mitch Biermann, Wenxuan Cai, Di Lang, Jack Hermsen, Luke Profio, Ying Zhou, Andras Czirok, Dona G. Isai, Brett N. Napiwocki, Adriana M. Rodriguez, Matthew E. Brown, Marites T. Woon, Annie Shao, Tianxiao Han, Donglim Park, Timothy A. Hacker, Wendy C. Crone, William J. Burlingham, Alexey V. Glukhov, Ying Ge, and Timothy J. Kamp. 2019. “Epigenetic Priming of Human Pluripotent Stem Cell-Derived Cardiac Progenitor Cells Accelerates Cardiomyocyte Maturation.” Stem Cells, 37, 7, Pp. 910-923. https://doi.org/10.1002/stem.3021Abstract
Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) exhibit a fetal phenotype that limits in vitro and therapeutic applications. Strategies to promote cardiomyocyte maturation have focused interventions on differentiated hPSC-CMs, but this study tests priming of early cardiac progenitor cells (CPCs) with polyinosinic-polycytidylic acid (pIC) to accelerate cardiomyocyte maturation. CPCs were differentiated from hPSCs using a monolayer differentiation protocol with defined small molecule Wnt temporal modulation, and pIC was added during the formation of early CPCs. pIC priming did not alter the expression of cell surface markers for CPCs (>80% KDR+/PDGFRα+), expression of common cardiac transcription factors, or final purity of differentiated hPSC-CMs (∼90%). However, CPC differentiation in basal medium revealed that pIC priming resulted in hPSC-CMs with enhanced maturity manifested by increased cell size, greater contractility, faster electrical upstrokes, increased oxidative metabolism, and more mature sarcomeric structure and composition. To investigate the mechanisms of CPC priming, RNAseq revealed that cardiac progenitor-stage pIC modulated early Notch signaling and cardiomyogenic transcriptional programs. Chromatin immunoprecipitation of CPCs showed that pIC treatment increased deposition of the H3K9ac activating epigenetic mark at core promoters of cardiac myofilament genes and the Notch ligand, JAG1. Inhibition of Notch signaling blocked the effects of pIC on differentiation and cardiomyocyte maturation. Furthermore, primed CPCs showed more robust formation of hPSC-CMs grafts when transplanted to the NSGW mouse kidney capsule. Overall, epigenetic modulation of CPCs with pIC accelerates cardiomyocyte maturation enabling basic research applications and potential therapeutic uses.
Kenneth Lay, Shaopeng Yuan, Shiri Gur-Cohen, Yuxuan Miao, Tianxiao Han, Shruti Naik, Amalia H Pasolli, Samantha B Larsen, and Elaine Fuchs. 12/6/2018. “Stem cells repurpose proliferation to contain a breach in their niche barrier.” eLife. https://doi.org/10.7554/eLife.41661Abstract
Adult stem cells are responsible for life-long tissue maintenance. They reside in and interact with specialized tissue microenvironments (niches). Using murine hair follicle as a model, we show that when junctional perturbations in the niche disrupt barrier function, adjacent stem cells dramatically change their transcriptome independent of bacterial invasion and become capable of directly signaling to and recruiting immune cells. Additionally, these stem cells elevate cell cycle transcripts which reduce their quiescence threshold, enabling them to selectively proliferate within this microenvironment of immune distress cues. However, rather than mobilizing to fuel new tissue regeneration, these ectopically proliferative stem cells remain within their niche to contain the breach. Together, our findings expose a potential communication relay system that operates from the niche to the stem cells to the immune system and back. The repurposing of proliferation by these stem cells patch the breached barrier, stoke the immune response and restore niche integrity.
Xiaoping Bao, Xiaojun Lian, Tongcheng Qian, Vijesh J Bhute, Tianxiao Han, and Sean P Palecek. 8/17/2017. “Directed differentiation and long-term maintenance of epicardial cells derived from human pluripotent stem cells under fully defined conditions.” Nature Protocols, 12, Pp. 1890–1900. https://doi.org/10.1038/nprot.2017.080Abstract
Here, we describe how to efficiently direct human pluripotent stem cells (hPSCs) differentiation into self-renewing epicardial cells in a completely defined, xeno-free system by temporal modulation of regulators of canonical Wnt signaling. Appropriate differentiation-stage-specific application of Gsk3 inhibitor, Wnt inhibitor, and Gsk3 inhibitor (GiWiGi) is sufficient to produce cells expressing epicardial markers and exhibiting epicardial phenotypes with a high yield and purity from multiple hPSC lines in 16 d. Characterization of differentiated cells is performed via flow cytometry and immunostaining to assess quantitative expression and localization of epicardial cell–specific proteins. In vitro differentiation into fibroblasts and smooth muscle cells (SMCs) is also described. In addition, culture in the presence of transforming growth factor (TGF)-β inhibitors allows long-term expansion of hPSC-derived epicardial cells (for at least 25 population doublings). Functional human epicardial cells differentiated via this protocol may constitute a potential cell source for heart disease modeling, drug screening, and cell-based therapeutic applications.
Xiaoping Bao, Vijesh J. Bhute, Tianxiao Han, Tongcheng Qian, Xiaojun Lian, and Sean P. Palecek. 2017. “Human pluripotent stem cell-derived epicardial progenitors can differentiate to endocardial-like endothelial cells.” Bioengineering & Translational Medicine, 2, 2, Pp. 191-201. https://doi.org/10.1002/btm2.10062Abstract
During heart development, epicardial progenitors contribute various cardiac lineages including smooth muscle cells, cardiac fibroblasts, and endothelial cells. However, their specific contribution to the human endothelium has not yet been resolved, at least in part due to the inability to expand and maintain human primary or pluripotent stem cell (hPSC)-derived epicardial cells. Here we first generated CDH5-2A-eGFP knock-in hPSC lines and differentiated them into self-renewing WT1+ epicardial cells, which gave rise to endothelial cells upon VEGF treatment in vitro. In addition, we found that the percentage of endothelial cells correlated with WT1 expression in a WT1-2A-eGFP reporter line. The resulting endothelial cells displayed many endocardium-like endothelial cell properties, including high expression levels of endocardial-specific markers, nutrient transporters and well-organized tight junctions. These findings suggest that human epicardial progenitors may have the capacity to form endocardial endothelium during development and have implications for heart regeneration and cardiac tissue engineering.
Xiaoping Bao, Xiaojun Lian, Timothy A. Hacker, Eric G. Schmuck, Tongcheng Qian, Vijesh J. Bhute, Tianxiao Han, Mengxuan Shi, Lauren Drowley, Alleyn T. Plowright, Qing-Dong Wang, Marie-Jose Goumans, and Sean P. Palecek. 12/5/2016. “Long-term self-renewing human epicardial cells generated from pluripotent stem cells under defined xeno-free conditions.” Nature Biomedical Engineering, 1, Pp. 0003. https://doi.org/10.1038/s41551-016-0003Abstract
The epicardium contributes both multi-lineage descendants and paracrine factors to the heart during cardiogenesis and cardiac repair, underscoring its potential for use in cardiac regenerative medicine. Yet little is known about the cellular and molecular mechanisms that regulate human epicardial development and regeneration. Here, we show that the temporal modulation of canonical Wnt signalling is sufficient for epicardial induction from six different human pluripotent stem cell (hPSC) lines, including a WT1-2A-eGFP knock-in reporter line, under chemically defined, xeno-free conditions. We also show that treatment with transforming growth factor beta (TGF-β)-signalling inhibitors permitted long-term expansion of the hPSC-derived epicardial cells, resulting in more than 25 population doublings of WT1+ cells in homogenous monolayers. The hPSC-derived epicardial cells were similar to primary epicardial cells both in vitro and in vivo, as determined by morphological and functional assays, including RNA sequencing. Our findings have implications for the understanding of self-renewal mechanisms of the epicardium and for epicardial regeneration using cellular or small-molecule therapies.
Daryl O. Nelson, Pratik A. Lalit, Mitch Biermann, Yogananda S. Markandeya, Deborah L. Capes, Luke Addesso, Gina Patel, Tianxiao Han, Manorama C. John, Patricia A. Powers, Karen M. Downs, Timothy J. Kamp, and Gary E. Lyons. 8/29/2016. “Irx4 Marks a Multipotent, Ventricular‐Specific Progenitor Cell.” Stem Cells, 34, 12, Pp. 2875-2888. https://doi.org/10.1002/stem.2486Abstract
While much progress has been made in the resolution of the cellular hierarchy underlying cardiogenesis, our understanding of chamber‐specific myocardium differentiation remains incomplete. To better understand ventricular myocardium differentiation, we targeted the ventricle‐specific gene, Irx4, in mouse embryonic stem cells to generate a reporter cell line. Using an antibiotic‐selection approach, we purified Irx4+ cells in vitro from differentiating embryoid bodies. The isolated Irx4+ cells proved to be highly proliferative and presented Cxcr4, Pdgfr‐alpha, Flk1, and Flt1 on the cell surface. Single Irx4+ ventricular progenitor cells (VPCs) exhibited cardiovascular potency, generating endothelial cells, smooth muscle cells, and ventricular myocytes in vitro. The ventricular specificity of the Irx4+ population was further demonstrated in vivo as VPCs injected into the cardiac crescent subsequently produced Mlc2v+ myocytes that exclusively contributed to the nascent ventricle at E9.5. These findings support the existence of a newly identified ventricular myocardial progenitor. This is the first report of a multipotent cardiac progenitor that contributes progeny specific to the ventricular myocardium.
Xiaoping Bao, Xiaojun Lian, Kaitlin K. Dunn, Mengxuan Shi, Tianxiao Han, Tongcheng Qian, Vijesh J. Bhute, Scott G. Canfield, and Sean P. Palecek. 7/2015. “Chemically-defined albumin-free differentiation of human pluripotent stem cells to endothelial progenitor cells.” Stem Cell Research, 15, 1, Pp. 122-129. https://doi.org/10.1016/j.scr.2015.05.004Abstract
Human pluripotent stem cell (hPSC)-derived endothelial cells and their progenitors are important for vascular research and therapeutic revascularization. Here, we report a completely defined endothelial progenitor differentiation platform that uses a minimalistic medium consisting of Dulbecco's modified eagle medium and ascorbic acid, lacking of albumin and growth factors. Following hPSC treatment with a GSK-3β inhibitor and culture in this medium, this protocol generates more than 30% multipotent CD34 + CD31 + endothelial progenitors that can be purified to > 95% CD34 + cells via magnetic activated cell sorting (MACS). These CD34 + progenitors are capable of differentiating into endothelial cells in serum-free inductive media. These hPSC-derived endothelial cells express key endothelial markers including CD31, VE-cadherin, and von Willebrand factor (vWF), exhibit endothelial-specific phenotypes and functions including tube formation and acetylated low-density lipoprotein (Ac-LDL) uptake. This fully defined platform should facilitate production of proliferative, xeno-free endothelial progenitor cells for both research and clinical applications.

Education

Harvard University
Ph.D. Candidate in Biological and Biomedical Sciences
 
University of Wisconsin-Madison
Bachelor of Science with Honors (BSc. Hons) in Biology
 
Victoria Junior College (Singapore)
Singapore-Cambridge GCE A-Level Certificate (AP-Equivalent High School Diploma)

Organizations

Harvard Graduate School of Arts and Sciences (GSAS) Consulting Club
Vice President of Professional Development (2020-Present)
Vice President of Case Competition (2019-2020)
 
Harvard Graduate School of Arts and Sciences (GSAS) Business Club
Associate Director of Entrepreneurship Initiative (2020-Present)

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