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We present an integrated approach to identify genetic mechanisms that control self-renewal in mouse embryonic stem cells. We use short hairpin RNA (shRNA) loss-of-function techniques to downregulate a set of gene products whose expression patterns suggest self-renewal regulatory functions. We focus on transcriptional regulators and identify seven genes for(More)
Mechanisms regulating self-renewal and cell fate decisions in mammalian stem cells are poorly understood. We determined global gene expression profiles for mouse and human hematopoietic stem cells and other stages of the hematopoietic hierarchy. Murine and human hematopoietic stem cells share a number of expressed gene products, which define key conserved(More)
In the developing cerebral cortex, neurons are born on a predictable schedule. Here we show in mice that the essential timing mechanism is programmed within individual progenitor cells, and its expression depends solely on cell-intrinsic and environmental factors generated within the clonal lineage. Multipotent progenitor cells undergo repeated asymmetric(More)
Neural stem cells (NSCs) persist throughout life in two forebrain areas: the subventricular zone (SVZ) and the hippocampus. Why forebrain NSCs self-renew more extensively than those from other regions remains unclear. Prior studies have shown that the polycomb factor Bmi-1 is necessary for NSC self-renewal and that it represses the cell cycle inhibitors(More)
The embryonic stem (ES) cell transcriptional and chromatin-modifying networks are critical for self-renewal maintenance. However, it remains unclear whether these networks functionally interact and, if so, what factors mediate such interactions. Here, we show that WD repeat domain 5 (Wdr5), a core member of the mammalian Trithorax (trxG) complex, positively(More)
Molecular regulation of embryonic stem cell (ESC) fate involves a coordinated interaction between epigenetic, transcriptional and translational mechanisms. It is unclear how these different molecular regulatory mechanisms interact to regulate changes in stem cell fate. Here we present a dynamic systems-level study of cell fate change in murine ESCs(More)
We have used retrovirus-mediated gene transfer to mark hematopoietic stem cells in vitro and have tracked the fate of these cells after their transplantation into lethally irradiated recipients. Several classes of stem cells are demonstrated, including cells whose progeny completely repopulate all hematopoietic lineages as well as cells that contribute(More)
We have characterized the fetal totipotent hematopoietic stem cell using a novel strategy that integrates physical analysis of cell properties and genetic analysis of in vivo developmental behavior. This approach allows the simultaneous isolation and in vivo characterization of any stem cell population. Using this procedure we demonstrate that a cell(More)
To elucidate the molecular biology of the hematopoietic stem cell, we have begun to isolate genes from murine cell populations enriched in stem cell activity. One such cDNA encodes a novel receptor tyrosine kinase, designated fetal liver kinase-2 or flk-2, which is related to the W locus gene product c-kit. Expression analyses suggest an extremely(More)
High content studies that profile mouse and human embryonic stem cells (m/hESCs) using various genome-wide technologies such as transcriptomics and proteomics are constantly being published. However, efforts to integrate such data to obtain a global view of the molecular circuitry in m/hESCs are lagging behind. Here, we present an m/hESC-centered database(More)