Asynchronous concurrent lactation (ACL) is an extreme lactation strategy in macropod marsupials including the tammar wallaby, that may hold the key to understanding local control of mammary epithelial cell function. Marsupials have a short gestation and a long lactation consisting of three phases; P2A, P2B and P3, representing early, mid and late lactation respectively and characterised by profound changes in milk composition. A lactating tammar is able to concurrently produce phase 2A and 3 milk from adjacent glands in order to feed a young newborn and an older sibling at heel. Physiological effectors of ACL remain unknown and in this study the extracellular matrix (ECM) is investigated for its role in switching mammary phenotypes between phases of tammar wallaby lactation. Using the level of expression of the genes for the phase specific markers tELP, tWAP, and tLLP-B representing phases 2A, 2B and 3 respectively we show for the first time that tammar wallaby mammary epithelial cells (WallMECs) extracted from P2B acquire P3 phenotype when cultured on P3 ECM. Similarly P2A cells acquire P2B phenotype when cultured on P2B ECM. We further demonstrate that changes in phase phenotype correlate with phase-specific changes in ECM composition. This study shows that progressive changes in ECM composition in individual mammary glands provide a local regulatory mechanism for milk protein gene expression thereby enabling the mammary glands to lactate independently.

译文

:同步并发泌乳(ACL)是包括tammar小袋鼠在内的大型足类有袋动物的一种极端泌乳策略,这可能是理解局部控制乳腺上皮细胞功能的关键。有袋动物的妊娠期短,哺乳期长,分为三个阶段。 P2A,P2B和P3分别代表泌乳早期,中期和晚期,其特征是牛奶成分发生了深刻变化。哺乳期的tammar能够同时从相邻的腺体中产生2A和3期乳汁,以喂养足跟的年轻新生儿和年长的兄弟姐妹。 ACL的生理效应仍然未知,在这项研究中,研究了细胞外基质(ECM)在tammar小袋鼠哺乳期之间切换乳腺表型中的作用。使用分别代表阶段2A,2B和3的阶段特异性标记tELP,tWAP和tLLP-B的基因表达水平,我们首次展示了从P2B提取的坦玛袋鼠乳腺上皮细胞(WallMEC)获得P3表型。在P3 ECM上培养时。类似地,当在P2B ECM上培养时,P2A细胞获得P2B表型。我们进一步证明,相表型的变化与ECM组成中的相特异性变化相关。这项研究表明,单个乳腺中ECM组成的逐步变化为乳蛋白基因表达提供了局部调节机制,从而使乳腺能够独立地泌乳。

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