Transcriptome Remodeling of Differentiated Cells during Chronological Ageing of Yeast Colonies: New Insights into Metabolic Differentiation

Abstract

We present the spatiotemporal metabolic differentiation of yeast cell subpopulations from upper, lower, and margin regions of colonies of different ages, based on comprehensive transcriptomic analysis. Furthermore, the analysis was extended to include smaller cell subpopulations identified previously by microscopy within fully differentiated U and L cells of aged colonies. New data from RNA-seq provides both spatial and temporal information on cell metabolic reprogramming during colony ageing and shows that cells at marginal positions are similar to upper cells, but both these cell types are metabolically distinct from cells localized to lower colony regions. As colonies age, dramatic metabolic reprogramming occurs in cells of upper regions, while changes in margin and lower cells are less prominent. Interestingly, whereas clear expression differences were identified between two L cell subpopulations, U cells (which adopt metabolic profiles, similar to those of tumor cells) form a more homogeneous cell population. The data identified crucial metabolic reprogramming events that arise de novo during colony ageing and are linked to U and L cell colony differentiation and support a role for mitochondria in this differentiation process.

Does senescence promote fitness in Caenorhabditis elegans by causing death?

“…Investigations of chronological or replicative aging in S. cerevisiae aging typically study dispersed cells in shaken culture or micromanipulated individual cells, with little consideration of ecological gerontology ( Dytham and Travis, 2006 ). However, in nature budding yeast exist mainly in spatially-structured, multicellular colonies ( Gourlay et al, 2006 ; Váchová et al, 2012 ), with distinct patterns of gene expression in different regions of the colony ( Wilkinson et al, 2018 ). PCD has been shown to occur in yeast colonies, mostly in cells in the centre of the colony, and removal of central cells reduces growth of cells at the periphery, suggesting that nutrients released by PCD in the colony core support peripheral cell growth ( Váchová et al, 2012 ; Váchová and Palková, 2005 ).…”

Long Noncoding RNAs in Yeast Cells and Differentiated Subpopulations of Yeast Colonies and Biofilms

“…We performed further studies using the more sensitive RNA sequencing (RNA-seq) technique. RNA-seq provided a detailed transcriptomic view of six cell subpopulations present in smooth BY4742 colonies grown on complete respiratory medium [ 17 ]: cells from upper, margin, and lower parts of colonies in two developmental phases (late acidic 6-day-old and alkali-phase 15-day-old). In parallel experiments, two subpopulations (a surface “aerial” cell subpopulation and a subpopulation of invasive “root” cells growing within the agar) from structured colony biofilms grown on the same medium were also studied [ 16 ] ( Figure 1 ).…”

“…Every gene located within 1.5 kB of (or antisense-overlapping) each lncRNA was identified to produce a list of lncRNA/gene pairs in any of the 5 different orientations ( Figure 2(a) ) considered. Previous expression profiling of subpopulations of smooth colonies and colony biofilms identified some metabolic similarities but even more differences [ 16 , 17 ]. Whereas some of the expression differences in individual genes may be caused by the fact that laboratory and wild strains forming smooth colonies and colony biofilms, respectively, are not isogenic, most of the differences are in agreement with the different lifestyles of yeast populations in smooth colonies (formed by either laboratory strains or domesticated wild strains) versus colony biofilms [ 1 , 5 ].…”

“…Cells localised to the upper and marginal regions of smooth colonies ( Figure 1 ) are somewhat similar in gene expression, protein production, and so on and are more different from cells localised to the lower regions of central colony areas [ 17 ]. lncRNA/gene antiregulation (where gene and lncRNA are antagonistically differentially expressed in the two subpopulations) and coregulation (agonistically differentially expressed) were highest when upper (U) and lower (L) cells were compared and lowest when upper and margin (M) cells were compared (Figures 2(b) and 2(c) ).…”

“…Here, we present a mini review of yeast lncRNAs and their previously described roles in regulating gene expression under various circumstances. In the second part of the review, we focus in more detail on lncRNAs that we have recently identified in differentiated subpopulations of cells from two distinct types of yeast populations [ 16 , 17 ], each of which uses unique strategies to cope with stress and ensure longevity of the population as a whole. These are complex colony biofilms formed by wild strains of Saccharomyces cerevisiae [ 18 ] and smooth colonies of S. cerevisiae laboratory strains [ 19 ] ( Figure 1 ).…”