Open Seminars of the Research Group on

 

Stochasticity and Control in the Dynamics and Diversity of Immune Repertories: an Example of Multi-Cellular Co-Operation

 

Monday, May 29, 2017, 12:00

at the Israel Institute for Advanced Studies, Room 128

 

 

 

Cellular heterogeneity in kidney tissues and tumors

 

Tomer Kalisky (BIU)

 

A major challenge in stem cell biology is to identify and molecularly characterize tissue-specific stem cells in tissues and tumors. In cancer, this is especially challenging since stem cells usually consist a very small fraction of the tumor “bulk”. To this end we used a combination of single cell technologies and next-generation sequencing to measure gene expression and sequence information from hundreds of individual cells in order to identify and molecularly characterize the cell sub-population repertoire of a developing fetal kidney (in both human and mouse) and Wilms’ tumor - a pediatric kidney tumor thought to originate from faulty differentiation of fetal developing tissues. We find that Wilms’ tumor is composed of cells resembling the most immature cell types of the developing fetal kidney. Moreover, we find that not one – but two populations are required for tumor initiation, suggesting that distorting the communication between these populations might pave the way for a cure. Finally, we show that different Wilms’ tumors create a continuum in gene expression space between archetypes that correspond to distinct cell types in the developing kidney.

 

 

Related Research Questions

 

  1. What are the main cell types that co-exist within the developing and adult kidney and what are the relations between them?
  2. How do these cell types change over the lifetime of the organism (pre-birth to adulthood) and how are they distorted in disease?
  3. Can we find unique markers for cancer stem cells? (both pediatric and adult tumors)

 

Suggested Reading

 

Kidney Development: Two Tales of Tubulogenesis

M. Little, K. Georgas, D. Pennisi, and L. Wilkinson

Current Topics in Developmental Biology, vol. 90, B. A. Thornhill and R. L. Chevalier, Eds. 2010, pp. 193–229.

 

Geometry of the Gene Expression Space of Individual Cells

Y. Korem, P. Szekely, Y. Hart, H. Sheftel, J. Hausser, A. Mayo, M. E. Rothenberg, T. Kalisky, and U. Alon

PLOS Comput. Biol., vol. 11, no. 7, p. e1004224, 2015.

 

Single-cell dissection of transcriptional heterogeneity in human colon tumors

P. Dalerba, T. Kalisky, D. Sahoo, P. S. Rajendran, M. E. Rothenberg, A. a Leyrat, S. Sim, J. Okamoto, D. M. Johnston, D. Qian, M. Zabala, J. Bueno, N. F. Neff, J. Wang, A. a Shelton, B. Visser, S. Hisamori, Y. Shimono, M. van de Wetering, H. Clevers, M. F. Clarke, and S. R. Quake

Nat. Biotechnol., vol. 29, no. 12, pp. 1120–1127, 2011.

 

 

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