Primitive hematopoietic stem cells are closely associated with discrete in vivo microenvironments. These "niches" are thought to provide the molecular signals that mediate stem cell differentiation and self renewal. We have dissected the fetal liver microenvironment into distinct cellular components by establishing an extensive panel of stromal cell lines. One particular cell line maintains repopulating stem cells for prolonged in vitro culture periods. A subtraction cloning strategy has yielded a cDNA which encodes a cell surface glycoprotein with a restricted pattern of expression among stromal cell lines. This molecule, previously identified as dlk/Pref-1, contains EGF-like repeats which are related to those in the Notch/Delta/Serrate family of proteins. We have investigated the potential role of this molecule in hematopoietic stem/progenitor cell regulation. We show that the dlk protein displays activity on purified stem cells by promoting the formation of "cobblestone areas" of proliferation. These cobblestone areas contain both primitive high-proliferative potential progenitors as well as in vivo repopulating stem cells.

As pilhas de haste hematopoietic primitivas são associadas pròxima com o discreto em microenvironments de vivo. Estes "niches" são pensados para fornecer os sinais molecular que medíam o differentiation da pilha de haste e a renovação do self. Nós dissected o microenvironment fetal do fígado em componentes celulares distintos estabelecendo um painel extensivo de linhas stromal da pilha. Uma linha particular da pilha mantem pilhas de haste repopulating para prolongado em períodos da cultura de vitro. Uma estratégia do cloning da subtração rendeu um DNA que codificasse um glycoprotein da superfície da pilha com um teste padrão restrito da expressão entre linhas stromal da pilha. Esta molécula, identificada previamente como dlk/Pref-1, contem EGF-como os repeats que são relacionados àqueles na família de Notch/Delta/Serrate das proteínas. Nós investigamos o papel potencial desta molécula no regulamento hematopoietic da pilha de stem/progenitor. Nós mostramos que a proteína do dlk indica a atividade em pilhas de haste purified promovendo a formação do "de áreas cobblestone" de proliferation. Estas áreas do cobblestone contêm ambos os progenitors potenciais elevados-proliferative primitivos as.well.as em pilhas de haste repopulating de vivo.

 
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