Howell Jonathan C, Lee Wei-Hua, Morrison Paul, Zhong Jin, Yoder Mervin C, Srour Edward F
Division of Hematology/Oncology and Indiana Elks Cancer Research Center, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Ann N Y Acad Sci. 2003 May;996:158-73. doi: 10.1111/j.1749-6632.2003.tb03244.x.
Pluripotential stem cells (PSCs) have been recently described in many tissues including skeletal muscle, brain, and bone marrow. However, the true nature of these cells is still unclear, and their precise definition has yet to be determined. We hypothesized that a common, rare population of PSCs with a broad tissue differentiation potential can be identified in multiple murine tissues and that these cells are capable of transdifferentiation into cells of different primordial germ layer origins in response to diverse microenvironmental cues. To examine this hypothesis, we isolated phenotypically defined cells from murine skeletal muscle and cultured these cells under different conditions tailored to promote differentiation into several cell types including myocytes. We report here that in conditions permissive for hematopoietic differentiation, muscle-derived CD45(-)Sca-1(+)c-kit(-) cells differentiated into cells expressing hematopoietic-specific mRNA; while in conditions promoting myogenic, neuronal, and adipocytic differentiation, cells morphologically typical of these cell types expressing tissue-specific markers were identified 9-14 days in culture. When CD45(-)Sca-1(+)c-kit(-) cells from muscle or bone marrow were transplanted intracerebellarly into Purkinje cell degenerative (pcd) mice, the behavior of these mice improved 28 days after transplantation relative to mice injected with vehicle alone, suggesting that these cells contributed to the appearance of functional neuronal cells that may have improved the ataxic condition characteristic of these mice. Phenotypic analysis of single cell suspensions prepared from brain, blood, and intestinal epithelium revealed the presence of CD45(-)Sca-1(+)c-kit(-) cells in varying degrees. These studies suggest that a phenotypically common, multipotent cell can be identified in different tissues and that this cell may represent a universal pluripotent stem cell residing at different levels in multiple murine tissues.
多能干细胞（PSCs）最近在包括骨骼肌、脑和骨髓在内的许多组织中被发现。然而，这些细胞的真正性质仍不清楚，其精确的定义也尚未确定。我们推测，在多种小鼠组织中可以鉴定出具有广泛组织分化潜能的常见、稀有多能干细胞群体，并且这些细胞能够响应不同的微环境信号转分化为不同原始胚层来源的细胞。为了验证这一假设，我们从小鼠骨骼肌中分离出表型明确的细胞，并在不同条件下培养这些细胞，这些条件旨在促进其分化为包括心肌细胞在内的几种细胞类型。我们在此报告，在允许造血分化的条件下，肌肉来源的CD45(-)Sca-1(+)c-kit(-)细胞分化为表达造血特异性mRNA的细胞；而在促进肌源性、神经元性和脂肪细胞分化的条件下，培养9 - 14天后可鉴定出形态上典型的表达组织特异性标志物的这些细胞类型。当将来自肌肉或骨髓的CD45(-)Sca-1(+)c-kit(-)细胞经小脑内移植到浦肯野细胞变性（pcd）小鼠中时，相对于仅注射赋形剂的小鼠，这些小鼠在移植后28天行为得到改善，这表明这些细胞有助于功能性神经元细胞的出现，可能改善了这些小鼠的共济失调状况。对从脑、血液和肠上皮制备的单细胞悬液进行表型分析，发现不同程度地存在CD45(-)Sca-1(+)c-kit(-)细胞。这些研究表明，在不同组织中可以鉴定出一种表型常见的多能细胞，并且这种细胞可能代表存在于多种小鼠组织不同水平的通用多能干细胞。
