Istituto Pasteur-Fondazione Cenci Bolognetti, Department of Cellular Biotechnologies and Haematology, Sapienza University of Rome, Rome, Italy.
Cell Death Differ. 2013 Aug;20(8):1116-23. doi: 10.1038/cdd.2013.49. Epub 2013 May 17.
Tissues of the adult organism maintain the homeostasis and respond to injury by means of progenitor/stem cell compartments capable to give rise to appropriate progeny. In organs composed by histotypes of different embryological origins (e.g. the liver), the tissue turnover may in theory involve different stem/precursor cells able to respond coordinately to physiological or pathological stimuli. In the liver, a progenitor cell compartment, giving rise to hepatocytes and cholangiocytes, can be activated by chronic injury inhibiting hepatocyte proliferation. The precursor compartment guaranteeing turnover of hepatic stellate cells (HSCs) (perisinusoidal cells implicated with the origin of the liver fibrosis) in adult organ is yet unveiled. We show here that epithelial and mesenchymal liver cells (hepatocytes and HSCs) may arise from a common progenitor. Sca+ murine progenitor cells were found to coexpress markers of epithelial and mesenchymal lineages and to give rise, within few generations, to cells that segregate the lineage-specific markers into two distinct subpopulations. Notably, these progenitor cells, clonally derived, when transplanted in healthy livers, were found to generate epithelial and mesenchymal liver-specific derivatives (i.e. hepatocytes and HSCs) properly integrated in the liver architecture. These evidences suggest the existence of a 'bona fide' organ-specific meso-endodermal precursor cell, thus profoundly modifying current models of adult progenitor commitment believed, so far, to be lineage-restricted. Heterotopic transplantations, which confirm the dual differentiation potentiality of those cells, indicates as tissue local cues are necessary to drive a full hepatic differentiation. These data provide first evidences for an adult stem/precursor cell capable to differentiate in both parenchymal and non-parenchymal organ-specific components and candidate the liver as the instructive site for the reservoir compartment of HSC precursors as yet non-localized in the adult.
成年生物组织通过祖/干细胞隔室维持内稳态并对损伤作出反应，这些隔室能够产生适当的后代。在由不同胚胎起源的组织类型组成的器官中（例如肝脏），组织更新可能理论上涉及能够协调响应生理或病理刺激的不同干细胞/前体细胞。在肝脏中，祖细胞隔室能够产生肝细胞和胆管细胞，可被抑制肝细胞增殖的慢性损伤激活。保证成年器官中肝星状细胞（HSCs）（与肝纤维化起源有关的窦周细胞）更新的前体细胞隔室尚未揭示。我们在这里表明，上皮和间充质肝细胞（肝细胞和 HSCs）可能来自共同的祖细胞。发现 Sca+ 小鼠祖细胞共同表达上皮和间充质谱系的标志物，并在几代内产生将谱系特异性标志物分离成两个不同亚群的细胞。值得注意的是，这些祖细胞，克隆衍生，当移植到健康肝脏中时，被发现能够产生适当整合到肝结构中的上皮和间充质肝特异性衍生物（即肝细胞和 HSCs）。这些证据表明存在“真正的”器官特异性中胚层前体细胞，从而深刻地改变了目前认为受限于谱系的成年祖细胞承诺的模型。异质移植证实了这些细胞的双重分化潜能，表明组织局部线索是驱动完全肝分化所必需的。这些数据为一种能够分化为实质和非实质器官特异性成分的成年干细胞/前体细胞提供了第一个证据，并候选肝脏作为迄今为止尚未在成年体内定位的 HSC 前体细胞储备隔室的指导部位。
