Embryonic Stem Cells and Squamous Epithelia

描述(申请人提供)：人类胚胎干细胞(ES)现在可用于研究体细胞类型的生成。就这一点而言，人的ES细胞比早期的小鼠ES细胞具有重要的优势。我们建议研究人类胚胎干细胞(WA01)在复层鳞状上皮中形成角质形成细胞的过程。已知ES细胞有能力在发育中的胚胎外产生这样的上皮细胞，因为当ES细胞被注射到SCID小鼠体内时，上皮就会发育。但我们的主要目的是在培养中找到促进ES细胞分化的条件，然后利用3T3支持分离出由这种分化产生的角质形成细胞株。我们将考察影响角质形成细胞发育的因素，以获得的数量的定量测量为标准，从而得出产生最大角质形成细胞产量的条件。如果可能，我们将确定分离的角质形成细胞所属的特定鳞状上皮。我们将尝试利用干细胞标记物寻找成熟角质形成细胞的体细胞干细胞前体进行鉴定。根据分离的角质形成细胞或角质形成细胞前体的性质，可以很容易地预见实际应用。

DESCRIPTION (provided by applicant): Human embryonic stem (ES) cells are now available for the study of the generation of somatic cell types. For this purpose, human ES cells have important advantages over the murine ES cells available earlier. We propose to study the generation of keratinocytes of stratified squamous epithelium from the human ES cells (WA01). ES cells are known to have the capacity to generate such epithelium outside the developing embryo, since the epithelium develops when the ES cells are injected into scid mice. But our main intention is to find conditions promoting differentiation of the ES cells in culture and then to isolate strains of keratinocytes resulting from that differentiation, using 3T3 support. We will examine the factors that influence the development of keratinocytes, using as criterion a quantitative measure of the number obtained, and in this way arrive at the conditions producing maximal yield of keratinocytes. We will identify, when possible, the specific squamous epithelium to which isolated keratinocytes belong. We will attempt to find somatic stem cell precursors of the mature keratinocytes using stem cell markers for their identification. Depending on the nature of the keratinocytes or keratinocyte precursors isolated, practical applications can be readily envisioned.