In vitro assays misrepresent in vivo lineage potentials of murine lymphoid progenitors
In vitro assays misrepresent in vivo lineage potentials of murine lymphoid progenitors
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DOI：
10.1182/blood-2010-05-287102
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发表时间：
2011-03-03
期刊：
影响因子：
20.3
通讯作者：
Weissman, Irving L.
中科院分区：
文献类型：
--
作者：
Ehrlich, Lauren I. Richie;Serwold, Thomas;Weissman, Irving L.
胸腺中T细胞祖细胞的身份一直存在争议，主要是因为许多研究对这些祖细胞是否保留骨髓潜能存在分歧。在使用各种体外和体内试验时，存在相互矛盾的报告。为了巩固这些不一致的发现，我们比较了2个假定的胸腺播种群体，共同淋巴祖细胞（CLP）和多能祖细胞（MPP），和最早的胸腺内祖细胞（DN 1）的髓系潜能，使用2种体外测定和体内读数。这些测定给出了矛盾的结果：CLP和DN 1在体外基质共培养物中对OP 9-DL 1显示出令人惊讶的稳健的髓样潜能，但在体内以及在甲基纤维素培养物中显示出很少的髓样潜能。另一方面，MPP在所有情况下都显示出强大的骨髓潜能。我们的结论是，基质共培养揭示了神秘的，但非生理性的，髓样淋巴祖细胞的潜力，提供了一个解释在该领域的矛盾的结果，并强调了使用在体内测定的重要性，用于确定生理谱系的潜力。（血。2011; 117（9）：2618-2624）
The identity of T-cell progenitors that seed the thymus has remained controversial, largely because many studies differ over whether these progenitors retain myeloid potential. Contradictory reports diverge in their use of various in vitro and in vivo assays. To consolidate these discordant findings, we compared the myeloid potential of 2 putative thymus seeding populations, common lymphoid progenitors (CLPs) and multipotent progenitors (MPPs), and the earliest intrathymic progenitor (DN1), using 2 in vitro assays and in vivo readouts. These assays gave contradictory results: CLP and DN1 displayed surprisingly robust myeloid potential on OP9-DL1 in vitro stromal cocultures but displayed little myeloid potential in vivo, as well as in methylcellulose cultures. MPP, on the other hand, displayed robust myeloid potential in all settings. We conclude that stromal cocultures reveal cryptic, but non-physiologic, myeloid potentials of lymphoid progenitors, providing an explanation for contradictory findings in the field and underscoring the importance of using in vivo assays for the determination of physiologic lineage potentials. (Blood. 2011; 117(9): 2618-2624)