Das Papri, Murthy Smrithi, Abbas Eshan, White Kristin, Arya Richa
Cytogenetics Laboratory, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi-221005.
Ashanagar Phase 2, Mulund (West), Mumbai 400080.
bioRxiv. 2024 Sep 5:2024.09.04.611161. doi: 10.1101/2024.09.04.611161.
The size of a cell is important for its function and physiology. Interestingly, size variation can be easily observed in clonally derived embryonic and hematopoietic stem cells. Here, we investigated the regulation of stem cell growth and its association with cell fate. We observed heterogeneous sizes of neuroblasts or neural stem cells (NSCs) in the ventral nerve cord (VNC). Specifically, thoracic NSCs were larger than those in the abdominal region of the VNC. Our research uncovered a significant role of the Hox gene () in the regulation of abdominal NSC growth. Developmental expression of AbdA retards their growth and delays mitotic entry compared to thoracic NSCs. The targeted loss of enhanced their growth and caused an earlier entry into mitosis with a faster cycling rate. Furthermore, ectopic expression of reduced the size of thoracic NSCs and delayed their entry into mitosis. We suggest that plays an instructive role in regulating NSC size and exit from quiescence. This study demonstrates for the first time the involvement of in NSC fate determination by regulating their growth, entry into mitosis and proliferation rate, and thus their potential to make appropriate number of progeny for CNS patterning.
细胞大小对其功能和生理学而言至关重要。有趣的是，在克隆衍生的胚胎干细胞和造血干细胞中能够轻易观察到大小差异。在此，我们研究了干细胞生长的调控及其与细胞命运的关联。我们观察到腹侧神经索（VNC）中神经母细胞或神经干细胞（NSC）大小各异。具体而言，胸部的神经干细胞比腹侧神经索腹部区域的神经干细胞更大。我们的研究揭示了Hox基因（）在调控腹部神经干细胞生长中具有重要作用。与胸部神经干细胞相比，AbdA的发育表达会抑制其生长并延迟有丝分裂的进入。的靶向缺失增强了它们的生长，并导致更早进入有丝分裂且循环速率更快。此外，的异位表达减小了胸部神经干细胞的大小并延迟了它们进入有丝分裂的时间。我们认为在调控神经干细胞大小和从静止状态退出方面发挥着指导性作用。这项研究首次证明了通过调控神经干细胞的生长、进入有丝分裂和增殖速率，进而参与神经干细胞命运的决定，从而使其有潜力为中枢神经系统模式形成产生适量的子代细胞。
