Harinder Singh
Research Summary / Selected Publications
Our research is motivated by two fundamental issues in developmental and molecular biology (i) how do regulatory networks of transcription factors specify the generation of distinct cell fates from stem cells and (ii) what kinds of molecular mechanisms are used to orchestrate lineage and stage-specific patterns of gene activity during cellular differentiation. The laboratory has focused our work in the hematopoietic system with particular emphasis on analyzing the development of various lineages of the immune system. The hematopoietic system is a leading developmental model for exploring the nature of the regulatory circuitry that enables a self-renewing pluripotent stem cell (HSC) to generate a complex set of differentiated cell types including erythrocytes, megakaryocytes, macrophages, granulocytes and B and T lymphocytes. We are interested in developing approaches for the directed and efficient generation of specific immune cells from embryonic stem cells. To explore molecular mechanisms that control cell type specific patterns of gene activity, we focus on immunoglobulin (Ig) gene loci in B lymphocytes because of their central role in development, distinctive structural organization and recombination dynamics.
Our research is motivated by two fundamental issues in developmental and molecular biology (i) how do regulatory networks of transcription factors specify the generation of distinct cell fates from stem cells and (ii) what kinds of molecular mechanisms are used to orchestrate lineage and stage-specific patterns of gene activity during cellular differentiation. The laboratory has focused our work in the hematopoietic system with particular emphasis on analyzing the development of various lineages of the immune system. The hematopoietic system is a leading developmental model for exploring the nature of the regulatory circuitry that enables a self-renewing pluripotent stem cell (HSC) to generate a complex set of differentiated cell types including erythrocytes, megakaryocytes, macrophages, granulocytes and B and T lymphocytes. We are interested in developing approaches for the directed and efficient generation of specific immune cells from embryonic stem cells. To explore molecular mechanisms that control cell type specific patterns of gene activity, we focus on immunoglobulin (Ig) gene loci in B lymphocytes because of their central role in development, distinctive structural organization and recombination dynamics.
Singh H. (2009).
Teeing up transcription on CpG islands.
Cell. 138:14-6.
Laslo P, Pongubala JM, Lancki DW, Singh H. (2008)
Gene regulatory networks directing myeloid and lymphoid cell fates within the immune system. Semin Immunol 20: 228-35.
Singh H . (2008) “PU.1, a shared transcriptional regulator of innate and adaptive immune cell fates.” J Immunol 181: 1595-6.
Medina, K. L., Pongubala, J. M., Reddy, K. L., Lancki, D. W., Dekoter, R., Kieslinger, M., Grosschedl, R. and Singh, H. (2004). "Assembling a gene regulatory network for specification of the B cell fate." Dev Cell 7: 607-17.
Lu, R., Medina, K. L., Lancki, D. W. and Singh, H. (2003). "IRF-4,8 orchestrate the pre-B-to-B transition in lymphocyte development." Genes Dev 17: 1703-8. PubMed Citation
Kosak, S. T., Skok, J. A., Medina, K. L., Riblet, R., Le Beau, M. M., Fisher, A. G. and Singh, H. (2002). "Subnuclear compartmentalization of immunoglobulin loci during lymphocyte development." Science 296: 158-62. PubMed Citation
Bertolino, E. and Singh, H. (2002). "POU/TBP cooperativity: a mechanism for enhancer action from a distance." Mol Cell 10: 397-407.
PubMed Citation
Walsh, J. C., DeKoter, R. P., Lee, H. J., Smith, E. D., Lancki, D. W., Gurish, M. F., Friend, D. S., Stevens, R. L., Anastasi, J. and Singh, H. (2002). "Cooperative and antagonistic interplay between PU.1 and GATA-2 in the specification of myeloid cell fates." Immunity 17: 665-76.
PubMed Citation
DeKoter, R. P., Lee, H. J. and Singh, H. (2002). "PU.1 regulates expression of the interleukin-7 receptor in lymphoid progenitors." Immunity 16: 297-309.
PubMed Citation
DeKoter, R. P. and Singh, H. (2000). "Regulation of B lymphocyte and macrophage development by graded expression of PU.1." Science 288: 1439-41. PubMed Citation
Glimcher, L.H. and Singh, H. (1999) Transcription factors in lymphocyte development - T and B cells get together. Cell 96:13-23. PubMed Citation
Singh H. (2009).
Teeing up transcription on CpG islands.
Cell. 138:14-6.
Laslo P, Pongubala JM, Lancki DW, Singh H. (2008)
Gene regulatory networks directing myeloid and lymphoid cell fates within the immune system. Semin Immunol 20: 228-35.
Singh H . (2008) “PU.1, a shared transcriptional regulator of innate and adaptive immune cell fates.” J Immunol 181: 1595-6.
Medina, K. L., Pongubala, J. M., Reddy, K. L., Lancki, D. W., Dekoter, R., Kieslinger, M., Grosschedl, R. and Singh, H. (2004). "Assembling a gene regulatory network for specification of the B cell fate." Dev Cell 7: 607-17.
Lu, R., Medina, K. L., Lancki, D. W. and Singh, H. (2003). "IRF-4,8 orchestrate the pre-B-to-B transition in lymphocyte development." Genes Dev 17: 1703-8. PubMed Citation
