Single Cell Analysis of Transcriptional Heterogeneity in the Early Developing Kidney
Conference Recording May 13, 2013
About the SpeakerSteve Potter's first paper, published in Nature, showed that mitochondrial DNA is maternally inherited. As postdoc at Harvard, with Gerry Rubin, he showed that the moderately repetitive fraction of DNA in Drosophila is made up of transposable elements. He has been a professor at Cincinnati Children’s Hospital since 1985. Cincinnati Children’s ranks number two in the US, only behind Harvard Children’s, as measured by NIH research dollars. Over the years he has remained at the technological forefront. His recent work has focused on HOX genes, kidney development, in particular the developmental decisions of the early progenitor cells, and craniofacial development.
There are many stages of development where a histologically homogeneous population of cells will give rise to multiple distinct lineages. We studied the earliest events in differentiation decisions using single cell global transcriptional profiling. In particular we examined the early metanephric mesenchyme cells of the kidney, which give rise to all of the tubular cells of the nephron as well as the stromal interstitial cells. We found evidence of both multipotential cells, expressing markers of distinct lineages, as well as lineage priming, with cells expressing genes associated with much later stages of differentiation. There was a surprising breadth of transcription profile types. In addition we examined the single cell gene expression profiles of the cranial neural crest cells, which give rise to muscle cartilage and bone of the face. The results help to define the stages at which the neural crest cells make their differentiation decisions, and the earliest transcriptional steps in these processes. General technical considerations in performing single cell gene expression profiling are discussed, as well as interpretation of the data. For example, how many cells must be examined, and how do you deal with technical and biological noise?
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