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STEM CELL GENETICS AND GENOMICS

Defining a Developmental Path to Neural Fate by Global Expression Profiling of Mouse Embryonic Stem Cells and Adult Neural Stem/Progenitor Cells

^a Developmental Genomics and Aging Section, Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA;
^b Institute for Stem Cell Research, Ospedale San Raffaele, Milan, Italy

Key Words. Embryonic stem cells • Principal component analysis • Neural commitment • Neural differentiation • Microarray

Correspondence: Minoru S.H. Ko, M.D., Ph.D., Developmental Genomics and Aging Section, Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. Telephone: 410-558-8359; Fax: 410-558-8331; e-mail: kom{at}mail.nih.gov

Received July 23, 2005; accepted for publication December 9, 2005.
To understand global features of gene expression changes during in vitro neural differentiation, we carried out the microarray analysis of embryonic stem cells (ESCs), embryonal carcinoma cells, and adult neural stem/progenitor (NS) cells. Expression profiling of ESCs during differentiation in monolayer culture revealed three distinct phases: undifferentiated ESCs, primitive ectoderm-like cells, and neural progenitor cells. Principal component (PC) analysis revealed that these cells were aligned on PC1 over the course of 6 days. This PC1 represents approximately 4,000 genes, the expression of which increased with neural commitment/differentiation. Furthermore, NS cells derived from adult brain and their differentiated cells were positioned along this PC axis further away from undifferentiated ESCs than embryonic stem–derived neural progenitors. We suggest that this PC1 defines a path to neural fate, providing a scale for the degree of commitment/differentiation.

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