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Xia Yun

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Nanyang Assistant Professor Xia Yun
PhD
Nanyang Assistant Professor
Principal Investigator, Stem Cell Lineage Specification & Organ Regeneration Laboratory

Team
 
  • Li Pin, Stem cell manager
  • Zhou Bingrui, PhD, Research Fellow
  • Low Jian Hui, PhD student
  • Su Chengxun, PhD student
  • Zhang Tian, Research Assistant
 
​Introduction
 
Xia Yun is a Nanyang Assistant Professor at Lee Kong Chian School of Medicine, Nanyang Technological University. Prior to this appointment, she had her postdoctoral training at the world-renowned Salk Institute for Biological Studies, La Jolla, US. Dr Xia obtained her BSc in Biology at China A​gricultural University and her PhD in Molecular and Cell Biology at National University of Singapore.

She has been working on stem cell in vitro lineage specification with a special focus on generating kidney-related cells. Her recent work led to the establishment of a novel method to differentiate human pluripotent stem cells into kidney ureteric bud progenitor-like cells using chemically defined medium. The generated human kidney cells form chimeric ureteric bud structures upon co-culture with embryonic mouse kidney cells (Fig 1). Her studies have been published in Nature Cell Biology and Nature Protocols, and highlighted by Nature Reviews Nephrology and Faculty 1000.

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Research Focus

​​​
3-Dimensional (3D) cell clusters generated from mammalian pluripotent or adult stem cells that self-organise into close-to-nature microanatomy with organ-specific differentiated cell types and tissue compartmentalisation in vitro. Differentiating human pluripotent stem cells (PSCs), including both embryonic stem cells and induced pluripotent stem cells, into 3D organoids represent the new era of in vitro lineage specification. Most if not all human PSCs-derived organoids are solely comprised of epithelial cell population, which is not sufficient to accomplish the organ function in most cases. To elaborate more complex and close-to-nature organ miniatures, additional cellular building blocks have been introduced to construct a high-order organoid. Despite various attempts, limited access has been achieved.

Kidney is a filtration organ, the function of which is dependent on its highly-elaborated 3D structure. Mammalian kidney is defined as a non-regenerative organ ascribing to the depletion of embryonic kidney progenitors during 36 weeks’ gestation in human and neonatal 2-3 days in mouse. One of the long-standing goals of our lab is to generate functionally mature kidney organoid from human PSCs. To realise this, the first and foremost step is to generate vascularised kidney organoid that is comprised of both the epithelial and vascular components. We have already established a highly efficient differentiation protocol to generate vascularised 3D kidney organoid (Fig 2).

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This novel differentiation platform allows us to streamline our lab projects into the following few directions:
  1. The lab is interested in studying early human embryonic kidney development in a dish with the goal of deciphering the lineage origin of nephron epithelium and renal vasculature.
  2. The lab is validating the in vivo potential of human PSCs-derived kidney organoids by transplantation into mouse model (Fig 3).
  3. The lab is using isogenic patient iPSCs-derived kidney organoids to model genetic polycystic kidney diseases (Fig 4).
  4. The lab is investigating the effect of physical conditions on in vitro kidney organoid differentiation.
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Selected Publications

Low JH, Li P, Chew E, Zhou B, …, Foo JN, Izpisua Belmonte JC, Xia Y. (2019). Generation of human PSC-derived kidney organoids with patterned nephron segments and a de novo vascular network. Cell Stem Cell. In press.  

Xia Y, & Izpisua Belmonte JC. (2019). Design approaches for generating organ constructs. Cell Stem Cell. 24(6):877-894. 

Xia Y, Montserrat N, Josep M, et al. (2017). Chapter 86: Lineage reprogramming toward kidney regeneration. Kidney Transplantation, Bioengineering, and Regeneration, 1167-75.

Li Z, Araoka T, …, Xia Y, et al. (2016). 3D culture supports long-term expansion of mouse and human nephrogenic progenitors. Cell Stem Cell, 19(4):516-29.

Sancho-Martinez I, Nivet E, Xia Y, et al. (2016). Establishment of human iPSC-based models for the study and targeting of glioma initiating cells. Nature Communications, (7):10743-57.

Xia Y, Sancho-Martinez I, Nivet E, et al. (2014). The generation of kidney organoids by differentiation of human pluripotent cells to ureteric bud progenitor-like cellsNature Protocols, 9(11):2693-704.

Pulecio J, Nivet E, …, Xia Y, et al. (2014). Conversion of human fibroblasts into monocyte-like progenitor cellsStem Cells, 32(11):2923-38.

Xia Y, Nivet E, Sancho-Martinez I, et al. (2013). Directed differentiation of human pluripotent cells to ureteric bud kidney progenitor-like cellsNature Cell Biology, 15(12):1507-15.

Montserrat N, Nivet E, …, Xia Y, et al. (2013). Reprogramming of human fibroblasts to pluripotency with lineage specifiersCell Stem Cell, 13(3):341-50.

Kurian L, Sancho-Martinez I, …, Xia Y, et al. (2013). Conversion of human fibroblasts to angioblast-like progenitor cells. Nature Methods, 10(1):77-83.

 
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