Skin Stem Cells

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Xin Hong Lim

Dr Xinhong Lim obtained his Ph.D. in Developmental Biology from Stanford University under the supervision of Roel Nusse, Ph.D. He is the recipient of numerous awards, including the A*STAR National Science Scholarship and the Institute of Medical Biology (IMB) Investigatorship in Skin Biology. As a Principal Investigator at IMB, his research on skin stem cell regulation has been awarded more than $6 million dollars in grant funding from A*STAR and a global Fortune 500 company. Dr Lim is also an Assistant Professor (Adjunct) at the LKC School of Medicine in Nanyang Technological University, Singapore, and the Cancer and Stem Cell Biology Programme, Duke-NUS Graduate Medical School. He has a Certificate in Innovation and Entrepreneurship from the Stanford University Graduate School of Business.         

Dr Lim is interested in the genetic circuitry that regulates tissue patterning, growth and repair. At Stanford University, he initiated and led numerous multidisciplinary collaborations, discovering completely new mechanisms of gene regulation and stem cell self-renewal in mammalian tissues including skin. This resulted in highly-cited publications in the most prestigious scientific journals, including Nature and Science. At IMB, he continues to work closely with international academic and industry partners to investigate the signals that pattern skin tissue and control skin cell fates, with a particular focus on sebaceous gland and hair regeneration and maintenance.  

Lim Xinhong’s Lab seeks to understand and alleviate common skin problems like hair loss and acne. These may result from imbalances in the behavior of stem cells that support the constant growth of skin and its appendages (hair and sebaceous glands). We aim to detect and correct such imbalances by studying stem cell behavior and the extrinsic signals that control it. Our studies involve international collaborations between academic and industrial partners, using the latest molecular and imaging tools in animal models and human clinical material.  

In the epidermis and hair follicle, we are probing the nature and composition of the stem cell population, and the molecular signals involved in maintaining stem cell identity. We have discovered novel molecular markers that may enable us to study and isolate epidermal and hair stem cells at higher purity for transplantation and disease modeling. We are further testing the functional significance of these markers using imaging and mathematical modelling.

Figure 1. One class of signals that controls skin stem cell fates is the Wnt family of signaling proteins. Wnt signaling regulates many aspects of animal development and regeneration, and the pathway is a major target for therapeutics. We found that skin stem cells balance self-renewal and induce differentiation by simultaneously producing autocrine Wnts and paracrine Wnt inhibitors targeted at their progeny. This mechanism of stem cell function is novel with respect to the skin and also the field of stem cells. (Source: Lim et al, Science 2013)

Much remains unknown about the sebaceous gland, the miniorgan that produces sebum on the skin and that may be involved in acne pathogenesis. To study the sebaceous gland, we have teamed up with Prof Maurice van Steensel to establish the Sebaceous Gland Lab. The Lab seeks to determine how mammalian sebaceous gland morphogenesis and function are controlled, using advanced –omics, precision genetic engineering and imaging techniques together with industrial collaborators. The ultimate goal is to build platforms for the development of novel drugs for sebum control and the treatment and prevention of acne and allied conditions. 

Figure 2. We are generating cellular models that recapitulate aspects of sebaceous gland biology. In this case, we have generated Asian sebocyte cell lines that accumulate lipid in response to physiological cues. (Source: Tham Khek Chian)

We are also interested in building new tools to study and influence stem cell behavior. In collaboration with bioengineers at NUS and NTU, we are developing and testing new methods of live imaging, biosensing, and drug delivery in the skin.

Skin Stem Cells Group Members

Research Fellow Carol Yu Ka Lou 
PhD Candidate LIM Beng Hui, Sophia
Research Officers 
Daniel Wu Zheng'An
  Jessica Xie Jiaxin

Sebaceous Gland Lab Group Members

Research Fellows Tham Khek Chian
  Tan Kai Xuan Keith
  Ang Siang Yun

Shang Wei

Chau Man Wah Rosanna
Research Officers Low Jun Xi Selwyn

Lee Pei Wen

Tan Yong Quan Alvin
  Faith Ng Cui En
  Melvin Chua Shen Wei

Rinkevich Y, Montoro DT, Contreras-Trujillo H, Harari-Steinberg O, Newman AM, Tsai JM, Lim X, Van-Amerongen R, Bowman A, Januszyk M, Pleniceanu O, Nusse R, Longaker MT, Weissman IL, Dekel B. In vivo clonal analysis reveals lineage-restricted progenitor characteristics in mammalian kidney development, maintenance, and regeneration. Cell Rep. 2014 May 22;7(4):1270-83. doi: 10.1016/j.celrep.2014.04.018. Epub 2014 May 15. PubMed PMID: 24835991. Link
Lim X, Tan SH, Koh WL, Chau RM, Yan KS, Kuo CJ, van Amerongen R, Klein AM, Nusse R. Interfollicular epidermal stem cells self-renew via autocrine Wnt signaling. Science. 2013 Dec 6;342(6163):1226-30. doi: 10.1126/science.1239730. PubMed PMID: 24311688; PubMed Central PMCID: PMC4081860. Link
Lim X, Nusse R. Wnt signaling in skin development, homeostasis, and disease. Cold Spring Harb Perspect Biol. 2013 Feb 1;5(2). pii: a008029. doi: 10.1101/cshperspect.a008029. Review. PubMed PMID: 23209129; PubMed Central PMCID: PMC3552514. Also published as a chapter in the book Signaling by Cold Spring Harbor Laboratory Press (2013). Link
McLean CY, Reno PL, Pollen AA, Bassan AI, Capellini TD, Guenther C, Indjeian VB, Lim X, Menke DB, Schaar BT, Wenger AM, Bejerano G, Kingsley DM. Human-specific loss of regulatory DNA and the evolution of human-specific traits. Nature. 2011 Mar 10;471(7337):216-9. doi: 10.1038/nature09774. PubMed PMID: 21390129; PubMed Central PMCID: PMC3071156. Link
Dombrowski C, Song SJ, Chuan P, Lim X, Susanto E, Sawyer AA, Woodruff MA, Hutmacher DW, Nurcombe V, Cool SM. Heparan sulfate mediates the proliferation and differentiation of rat mesenchymal stem cells. Stem Cells Dev. 2009 May;18(4):661-70. doi: 10.1089/scd.2008.0157. PubMed PMID: 18690792. Link
Lim X, Bless DM, Muñoz-Del-Río A, Welham NV. Changes in cytokine signaling and extracellular matrix production induced by inflammatory factors in cultured vocal fold fibroblasts. Ann Otol Rhinol Laryngol. 2008 Mar;117(3):227-38. PubMed PMID: 18444484. Link