A Single Cell Transcriptomic Atlas Characterizes Aging Tissues in the Mouse, bioRxiv, 2019-06-08
AbstractAging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death 1. Despite rapid advances over recent years 2, many of the molecular and cellular processes which underlie progressive loss of healthy physiology are poorly understood. To gain a better insight into these processes we have created a single cell transcriptomic atlas across the life span of Mus musculus which includes data from 18 tissues and organs. We discovered cell-specific changes occurring across multiple cell types and organs, as well as age related changes in the cellular composition of different organs. Using single-cell transcriptomic data we were able to assess cell type specific manifestations of different hallmarks of aging, such as senescence 3, changes in the activity of metabolic pathways 4, depletion of stem-cell populations 5, genomic instability 6 and the role of inflammation as well as other changes in the organism’s immune system2. This Tabula Muris Senis provides a wealth of new molecular information about how the most significant hallmarks of aging are reflected in a broad range of tissues and cell types.
biorxiv cell-biology 100-200-users 2019Light-regulated collective contractility in a multicellular choanoflagellate, bioRxiv, 2019-06-07
AbstractCollective cell contractions that generate global tissue deformations are a signature feature of animal movement and morphogenesis. Nonetheless, the ancestry of collective contractility in animals remains mysterious. While surveying the Caribbean island of Curaçao for choanoflagellates, the closest living relatives of animals, we isolated a previously undescribed species (here namedChoanoeca flexasp. nov.), that forms multicellular cup-shaped colonies. The colonies rapidly invert their curvature in response to changing light levels, which they detect through a rhodopsin-cGMP pathway. Inversion requires actomyosin-mediated apical contractility and allows alternation between feeding and swimming behavior.C. flexathus rapidly converts sensory inputs directly into multicellular contractions. In this respect, it may inform reconstructions of hypothesized animal ancestors that existed before the evolution of specialized sensory and contractile cells.One Sentence SummaryA newly described choanoflagellate species forms cup-shaped colonies that reversibly invert their curvature in response to light.
biorxiv cell-biology 200-500-users 2019Multiscale activity imaging in the mammary gland reveals how oxytocin enables lactation, bioRxiv, 2019-06-03
AbstractThe mammary epithelium is indispensable for the continued survival of more than 5000 mammalian species. For some, the volume of milk ejected in a single day exceeds their entire blood volume. Here, we unveil the spatiotemporal properties of physiological signals that orchestrate milk ejection. Using quantitative, multidimensional imaging of mammary cell ensembles, we reveal how stimulus-evoked Ca2+ oscillations couple to contraction in basal epithelial cells. Moreover, we show that Ca2+-dependent contractions generate the requisite force to physically-deform the innermost layer of luminal cells, forcing them to discharge the fluid that they produced and housed. Through the collective action of thousands of these biological positive-displacement pumps, each linked to a contractile ductal network, milk is delivered into the mouth of the dependent neonate, seconds after the command.One Sentence SummaryThis study provides a window into the organization, dynamics and role of epithelial Ca2+ responses in the organ principally responsible for sustaining neonatal life in mammals.
biorxiv cell-biology 200-500-users 2019Unconventional cell division cycles from marine-derived yeasts, bioRxiv, 2019-06-02
AbstractFungi have been found in every marine habitat that has been explored, however, the diversity and functions of fungi in the ocean are poorly understood. In this study, fungi were cultured from the marine environment in the vicinity of Woods Hole, MA, USA including from plankton, sponge and coral. Our sampling resulted in 36 unique species across 20 genera. We observed many isolates by time-lapse differential interference contrast (DIC) microscopy and analyzed modes of growth and division. Several black yeasts displayed highly unconventional cell division cycles compared to those of traditional model yeast systems. Black yeasts have been found in habitats inhospitable to other life and are known for halotolerance, virulence, and stress-resistance. We find that this group of yeasts also shows remarkable plasticity in terms of cell size control, modes of cell division, and cell polarity. Unexpected behaviors include division through a combination of fission and budding, production of multiple simultaneous buds, and cell division by sequential orthogonal septations. These marine-derived yeasts reveal alternative mechanisms for cell division cycles that seem likely to expand the repertoire of rules established from classic model system yeasts.
biorxiv cell-biology 100-200-users 2019Mammary mechanobiology mechanically-activated ion channels in lactation and involution, bioRxiv, 2019-05-27
AbstractA mother’s ability to produce a nutritionally-complete neonatal food source has provided a powerful evolutionary advantage to mammals. Milk production by secretory mammary epithelial cells is adaptive, its release is exquisitely timed and its own glandular stagnation with the permanent cessation of suckling triggers the programmed cell death and tissue remodeling that enables female mammals to nurse successive progeny. Both chemical and mechanical signals control epithelial expansion, function and remodeling. Despite this duality of input, however, the nature and function of mechanical forces in the mammary gland remain unknown. Here, we characterize the mammary force landscape and the capacity of luminal and basal epithelial cells to experience and exert force. We explore the molecular instruments for force-sensing in the mammary gland and the physiological requirement for PIEZO1 in lactation and involution. Our study supports the existence of a multifaceted system of chemical and mechanical sensing in the mammary gland, and a protective redundancy that ensures continued lactational competence and offspring survival.
biorxiv cell-biology 500+-users 2019Cellular and Molecular Probing of Intact Transparent Human Organs, bioRxiv, 2019-05-21
SUMMARYOptical tissue transparency permits cellular and molecular investigation of complex tissues in 3D, a fundamental need in biomedical sciences. Adult human organs are particularly challenging for this approach, owing to the accumulation of dense and sturdy molecules in decades-aged human tissues. Here, we introduce SHANEL method utilizing a new tissue permeabilization approach to clear and label stiff human organs. We used SHANEL to generate the first intact transparent adult human brain and kidney, and perform 3D histology using antibodies and dyes in centimeters depth. Thereby, we revealed structural details of sclera, iris and suspensory ligament in the human eye, and the vessels and glomeruli in the human kidney. We also applied SHANEL on transgenic pig organs to map complex structures of EGFP expressing beta cells in >10 cm size pancreas. Overall, SHANEL is a robust and unbiased technology to chart the cellular and molecular architecture of intact large mammalian organs.Graphical Abstract<jatsfig id=ufig1 position=float orientation=portrait fig-type=figure><jatsgraphic xmlnsxlink=httpwww.w3.org1999xlink xlinkhref=643908v1_ufig1 position=float orientation=portrait >Supplementary Movies of SHANEL are available at <jatsext-link xmlnsxlink=httpwww.w3.org1999xlink ext-link-type=uri xlinkhref=httpdiscotechnologies.orgSHANEL>httpdiscotechnologies.orgSHANEL<jatsext-link>
biorxiv cell-biology 500+-users 2019