Biology subjects

Nagasaka, A.

Publications and source records attributed to Nagasaka, A..

4 recordsLinked to original sources

bioRxiv2024

Alteration of long and short-term hematopoietic stem cell ratio causes myeloid-biased hematopoiesis

Myeloid-biased hematopoiesis is a well-known age-related alteration. Several possibilities, including myeloid-biased hematopoietic stem cell (HSC) clones, may explain this. However, the precise mechanisms remain controversial. Utilizing the Hoxb5 reporter system to prospectively isolate long-term HSCs (LT-HSCs) and short-term HSCs (ST-HSCs), we found that young and aged LT-HSCs co-transplanted into the same recipients demonstrated nearly equivalent myeloid lineage output, contrary to the theory of myeloid-biased HSC clones. Transcriptomics indicated no significant myeloid gene enrichment in aged LT-HSCs compared to their young counterparts. Instead, transplanting reconstituted young HSCs with the ratio of LT/ST-HSCs seen in aged mice can significantly skew the lineage output to myeloid cells. In addition, while the niche environment in the bone marrow minimally affects myeloid-biased hematopoiesis, aged thymi and spleens substantially hinder lymphoid hematopoiesis, resulting in further myeloid-domination. Thus, we demonstrate that myeloid-biased hematopoiesis in aged organisms originates due to alteration of the ratio between LT-HSCs and ST-HSCs rather than in heterogeneous HSC clones with various cell fates.

developmental biology↗

bioRxiv2022

Stiffness of primordial germ cells is required for their extravasation in avian embryos

During metastasis intravascularly circulating cancer cells undergo extravasation, which frequently takes place in vascular capillary beds 1-3. It remains poorly understood how the extravasation in the capillary beds is regulated. To address this question, chicken primordial germ cells (PGCs) serve as a powerful model since they circulate in blood stream and extravasate at a specific site of capillary bed near the forming gonad 4-6. The extravasation consists of two steps, the intravascular arrest of cells and their subsequent transmigration through the endothelial lining. We here demonstrate with live imaging at a single cell level in vivo that the arrest of PGCs is predominantly governed by occlusion at a narrow path in the capillary bed. In addition, this occlusion is enabled by a hightened stiffness of the PGCs, revealed by atomic force microscopy indentation analyses. The PGCs stiffness is regulated by actin polymerization: inhibition of the actin function causes not only a failure of PGC occlusion in the capillary bed, but also a failure of PGC colonization in the gonads at later stages. Following the occlusion, PGCs reset their stiffness to soften in order to squeeze through the endothelial lining as they transmigrate. The discovery of F-actin-mediated stiffness in pre-extravasating cells provides a model for understanding of dynamic mechanism by which other cells, including metastasizing cancer cells, extravasate in capillary beds.

developmental biology↗

bioRxiv2021

Mechanical collaboration between the embryonic brain and the surrounding scalp tissues

During brain enlargement between embryonic day (E) 11 and E13, within the limited mouse cranial space enclosed by the scalp consisting of epidermal and preosteogenic mesenchymal layers, the angle between the pons and the medulla decreases. This raises the possibility that the scalp, upon being pushed outwardly by the brain and stretched, in return inwardly recoils to confine and fold the brain. Our stress-releasing tests showed that the scalp recoiled to shrink more extensively at E12~13 than at E15~16 and that the in vivo pre-stretch prerequisite for this recoil response depended physically on the brain (pressurization at 77~93 Pa) and on actomyosin and elastin within the scalp layers. Under non-stretched conditions, scalp cell proliferation declined, while re-stretching of the shrunken scalp rescued proliferation. In scalp-removed heads, pons-medulla folding was reduced, and the spreading of ink from the lateral ventricle to the spinal cord that occurred in scalp-intact embryos (with >5 l injection) was lost, suggesting that the scalp plays roles in brain morphogenesis and cerebrospinal fluid homeostasis. Thus, the brain and the scalp mechanically interact and collaborate.

developmental biology↗

bioRxiv2019

Dorsal-to-ventral neocortical expansion is physically primed by ventral streaming of early embryonic preplate neurons

Mammalian neocortex exhibits a disproportionally \"luxurious\" representation of somatotopies in its lateral region, which depends on dorsal-to-ventral expansion of the pallium during development. Despite recent studies elucidating the molecular mechanisms underlying the cortical arealization/patterning, we know very little about how the cortex expands ventrally and the nature of the underlying force-generating events. We found that neurons born earliest (at embryonic day 10 [E10]) in the mouse pallium migrated ventrally and then extended corticofugal axons, which together formed a morphogenetic flow of the preplate that persists until E13. These neurons exerted pulling and pushing forces at the process and the soma, respectively. Ablation of these E10-born neurons attenuated both deflection of radial glial fibers (by E13) and extension of the cortical plate (by E14), which should occur ventrally, and subsequently shrank the postnatal neocortical map dorsally. This previously unrecognized preplate stream physically primes neocortical expansion and somatotopic map formation.

neuroscience↗