Asymmetric midbody inheritance during germline stem cell division in Drosophila

描述（由申请人提供）：不对称干细胞分裂通过产生一个干细胞和一个分化细胞而有助于组织稳态。不对称干细胞分裂可以通过内在命运决定子的不对称分离和/或子细胞不对称放置到不同的微环境（即，干细胞龛内与干细胞龛外，其指定干细胞身份）。然而，管理不对称命运决定的分子和细胞机制知之甚少。人们早就知道，即使在表面上对称分裂的细胞中，也存在不对称性。例如，在胞质分裂的最后一步，即胞质分裂，质膜分解成两个独立的膜通常只发生在中间体的一侧，中间体是连接两个姐妹细胞的结构。这导致另一侧的细胞继承了中间体环（MR）。这种不对称性与中心体年龄相关;含有母亲中心体的子细胞继承了MR残余，这表明复杂的调节机制控制着这一过程。然而，尽管有这些有趣的观察结果，我们还不知道这些不对称是否有任何生物学意义。 我们建议研究GSC胞质分裂过程中MR不对称遗传的机制和相关性，使用果蝇生殖系干细胞（GSC），这提供了一个独特的机会来研究多细胞组织结构和发育背景下的细胞不对称性。我们的初步研究表明，男性和女性GSCs的MR遗传是刻板不对称的，这显然涉及中心体年龄和自噬调控的不对称。我们将通过检查MR遗传缺陷的后果来研究这种现象的潜在分子机制和生物学相关性。 我们的目的是了解干细胞分裂过程中不对称胞质分裂的相关性。从拟议的研究中获得的结果可能提供一种操纵干细胞行为用于治疗用途或抑制癌症生长的方法。 公共卫生相关性：我们的目的是了解干细胞分裂过程中不对称胞质分裂的相关性。从拟议的研究中获得的结果可能提供一种操纵干细胞行为用于治疗用途或抑制癌症生长的方法。

DESCRIPTION (provided by applicant): Asymmetric stem cell division contributes to tissue homeostasis by generating one stem cell and one differentiating cell. Asymmetric stem cell division can be achieved by asymmetric segregation of intrinsic fate determinants and/or asymmetric placement of daughter cells into different microenvironments (i.e., inside vs. outside of the stem cell niche, which specifies stem cell identity). Yet, the molecular and cellular mechanisms that govern asymmetric fate decision are poorly understood. It has long been known that asymmetries exist even in apparently symmetrically dividing cells. For example, during the final step of cytokinesis known as abscission, the resolution of the plasma membrane into two separate membranes normally occurs from only one side of the midbody, the structure that connects the two sister cells. This results in inheritance of the midbody ring (MR) by the cell on the other side. This asymmetry has been correlated with centrosome age; the daughter cell containing the mother centrosome inherits the MR remnant, suggesting that elaborate regulatory mechanisms control this process. However, in spite of these intriguing observations, it is not known whether these asymmetries have any biological relevance. We propose to investigate the mechanism and relevance of asymmetric MR inheritance during GSC cytokinesis, using Drosophila germline stem cells (GSCs), which offer a unique opportunity to investigate cellular asymmetries in the context of multicellular tissue architecture and development. Our preliminary study suggests that the MR inheritance during male and female GSCs is stereotypically asymmetric, which apparently involves asymmetry in centrosomal age and regulation of autophagy. We will investigate the underlying molecular mechanism and the biological relevance of this phenomenon, by examining the consequence(s) of defective MR inheritance. Lay summary: We aim to understand the relevance of asymmetric cytokinesis during stem cell division. Results obtained from the proposed research may provide a means to manipulate stem cell behavior for therapeutic usage or inhibition of cancer growth. PUBLIC HEALTH RELEVANCE: We aim to understand the relevance of asymmetric cytokinesis during stem cell division. Results obtained from the proposed research may provide a means to manipulate stem cell behavior for therapeutic usage or inhibition of cancer growth.