Regulation of Cell Identity and Cell Growth

NAnog-GFP expressing mouse ESC colony (Schaniel et al, 2006/2009)

There are over 200 different cell types in the human body, each with a specialized function, which arise during development and adult tissue homeostasis from transient or established progenitor cells resident in tissues and organs. Two emerging themes in disease research emphasize why it is crucial that we understand how cell identities are formed and maintained in mammals. First is the notion that cancer cells may arise from maligned development programs. In addition to co-opting growth and survival promoting pathways, tumor cells hijack molecular pathways that are normally involved in developmental processes such as cell fate determination. The existence of cancer stem cells, which may play vital roles in tumor progression, maintenance, and recurrence, underscores this notion. Second is the notion that, with the successful isolation of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), we can develop techniques to harness their developmental potential in the laboratory for clinical applications, such as cell replacement therapies for neurodegeneration, spinal cord injury, liver dysfunction, severe burns, blood disorders, etc. Through the use of defined, in vitro embryonic and somatic stem cell systems, we will find and characterize gene products affecting stem cell self-renewal, differentiation, proliferation, and survival.

To date we have examined several aspects of regulation of cell identify and cell growth:

How mouse embryonic stem cells exit the pluripotent "ground" state (Schaniel et al., Nature Methods 2008; Schaniel et al., Stem Cells 2009; Betschinger et al., Cell 2013).

How human embryonic stem cells exit the pluripotent "ground" state (Mathieu et al., in preparation w/ Dr. Hannele Ruohola-Baker's group).

How human hematopoietic stem cell exit the multipotent state (Chen et al., Genes and Dev. 2012).

How hematopoietic progenitors commit to the erythroid lineage (Kuppers et al., in preparation).

How cells regulate the G0-quiescent-like state during cell cycle progression (Feldman et al., in preparation).