A secreted factor and cyclic AMP jointly regulate cell-type-specific gene expression in Dictyostelium discoideum.

We are studying cell differentiation in Dictyostelium discoideum by examining the regulation of genes that are preferentially expressed in different cell types. A system has been established in which prestalk- and prespore-cell-specific genes are expressed in single cells in response to culture conditions. We confirm our previous results showing that cyclic AMP induces prestalk genes and now show that it is also required for prespore gene induction. The expression of both classes of genes is additionally dependent on the presence of a factor(s) secreted by developing cells which we call conditioned medium factor(s). An assay for conditioned medium factor(s) shows that it is detectable within 2.5 h after the onset of development. Conditioned medium factor(s) also promotes the expression of genes induced early in development, but has no detectable effect on the expression of actin genes and a gene expressed maximally in vegetative cells. In the presence of conditioned medium factor(s), exogenous cyclic AMP at the onset of starvation fails to induce the prespore and prestalk genes. The addition of cyclic AMP between 2 and 12 h of starvation results in rapid prestalk gene expression, whereas prespore genes are induced at an invarient time (approximately 18 h after the onset of starvation). These data suggest that cyclic AMP and conditioned medium factor(s) are sufficient for prestalk gene induction, whereas an additional parameter(s) is involved in the control of prespore gene induction. In contrast to several previous studies, we show that multicellularity is not essential for the expression of either prespore or prestalk genes. These data indicate that prespore and prestalk genes have cell-type-specific as well as shared regulatory factors.

Download Full-text

Improved estimation of cell type-specific gene expression through deconvolution of bulk tissues with matrix completion

10.1101/2021.06.30.450493 ◽

2021 ◽

Author(s):

Weixu Wang ◽

Jun Yao ◽

Yi Wang ◽

Chao Zhang ◽

Wei Tao ◽

...

Keyword(s):

Gene Expression ◽

Single Cells ◽

Matrix Completion ◽

Superior Performance ◽

Specific Gene ◽

Rna Seq ◽

Cell Type ◽

Specific Gene Expression ◽

Large Patient ◽

Cell Type Specific

Cell type-specific gene expression (CSE) brings novel biological insights into both physiological and pathological processes compared with bulk tissue gene expression. Although fluorescence-activated cell sorting (FACS) and single-cell RNA sequencing (scRNA-seq) are two widely used techniques to detect gene expression in a cell type-specific manner, the constraints of cost and labor force make it impractical as a routine on large patient cohorts. Here, we present ENIGMA, an algorithm that deconvolutes bulk RNA-seq into cell type-specific expression matrices and cell type fraction matrices without the need of physical sorting or sequencing of single cells. ENIGMA used cell type signature matrix generated from either FACS RNA-seq or scRNA-seq as reference, and applied matrix completion technique to achieve fast and accurate deconvolution. We demonstrated the superior performance of ENIGMA to previously published algorithms (TCA, bMIND and CIBERSORTx) while requiring much less running time on both simulated and realistic datasets. To prove its value in biological discovery, we applied ENIGMA to bulk RNA-seq from arthritis patients and revealed a pseudo-differentiation trajectory that could reflect monocyte to macrophage transition. We also applied ENIGMA to bulk RNA-seq data of pancreatic islet tissue from type 2 diabetes (T2D) patients and discovered a beta cell-specific gene co-expression module related to senescence and apoptosis that possibly contributed to the pathogenesis of T2D. Together, ENIGMA provides a new framework to improve the CSE estimation by integrating FACS RNA-seq and scRNA-seq with tissue bulk RNA-seq data, and will extend our understandings about cell heterogeneity on population level with no need for experimental tissue disaggregation.

Download Full-text

Dictyostelium discoideum Sir2D modulates cell-type specific gene expression and is involved in autophagy

The International Journal of Developmental Biology ◽

10.1387/ijdb.160038ss ◽

2017 ◽

Vol 61 (1-2) ◽

pp. 95-104 ◽

Cited By ~ 8

Author(s):

Rakhee Lohia ◽

Punita Jain ◽

Mukul Jain ◽

Pradeep Kumar Burma ◽

Anju Shrivastava ◽

...

Keyword(s):

Gene Expression ◽

Dictyostelium Discoideum ◽

Specific Gene ◽

Cell Type ◽

Specific Gene Expression ◽

Cell Type Specific

Download Full-text

Abberant chemotaxis and differentiation in Dictyostelium mutant fgdC with a defective regulation of receptor-stimulated phosphoinositidase C

Journal of Cell Science ◽

10.1242/jcs.100.4.825 ◽

1991 ◽

Vol 100 (4) ◽

pp. 825-831 ◽

Cited By ~ 3

Author(s):

A.A. Bominaar ◽

F. Kesbeke ◽

B.E. Snaar-Jagalska ◽

D.J. Peters ◽

P. Schaap ◽

...

Keyword(s):

Gene Expression ◽

Cyclic Amp ◽

Adenylate Cyclase ◽

Guanylate Cyclase ◽

Specific Gene ◽

Wild Type ◽

Cell Type ◽

Surface Receptors ◽

Cell Type Specific ◽

Stimulation Of

Dictyostelium cells use extracellular cyclic AMP both as a chemoattractant and as a morphogen inducing cell-type-specific gene expression. Cyclic AMP binds to surface receptors, activates one or more G-proteins, and stimulates adenylate cyclase, guanylate cyclase and phosphoinositidase C. Mutant fgdC showed aberrant chemotaxis, and was devoid of cyclic AMP-induced gene expression and differentiation. Both the receptor- and G-protein-mediated stimulation of adenylate cyclase and guanylate cyclase were unaltered in mutant fgdC as compared to wild-type cells. In wild-type cells phosphoinositidase C was activated about twofold by the cyclic AMP receptor. In mutant fgdC cells, however, the enzyme was inhibited by about 60%. These results suggest that phosphoinositidase C is regulated by a receptor-operated activation/inhibition switch that is defective in mutant fgdC. We conclude that activation of phosphoinositidase C is essential for Dictyostelium development.

Download Full-text

An integrated analysis of cell-type specific gene expression reveals genes regulated by REVOLUTA and KANADI1 in the Arabidopsis shoot apical meristem

PLoS Genetics ◽

10.1371/journal.pgen.1008661 ◽

2020 ◽

Vol 16 (4) ◽

pp. e1008661 ◽

Cited By ~ 2

Author(s):

Hasthi Ram ◽

Sudeep Sahadevan ◽

Nittaya Gale ◽

Monica Pia Caggiano ◽

Xiulian Yu ◽

...

Keyword(s):

Gene Expression ◽

Shoot Apical Meristem ◽

Apical Meristem ◽

Integrated Analysis ◽

Specific Gene ◽

Cell Type ◽

Specific Gene Expression ◽

Cell Type Specific

Download Full-text

Construction and use of GFP reporter vectors for analysis of cell-type-specific gene expression in Nostoc punctiforme

Journal of Microbiological Methods ◽

10.1016/j.mimet.2004.06.009 ◽

2004 ◽

Vol 59 (2) ◽

pp. 181-188 ◽

Cited By ~ 27

Author(s):

Claudia Argueta ◽

Kamile Yuksek ◽

Michael Summers

Keyword(s):

Gene Expression ◽

Specific Gene ◽

Nostoc Punctiforme ◽

Cell Type ◽

Specific Gene Expression ◽

Gfp Reporter ◽

Cell Type Specific

Download Full-text

Functional Promiscuity of Gene Regulation by Serpentine Receptors in Dictyostelium discoideum

Molecular and Cellular Biology ◽

10.1128/mcb.18.10.5744 ◽

1998 ◽

Vol 18 (10) ◽

pp. 5744-5749 ◽

Cited By ~ 15

Author(s):

Irene Verkerke-Van Wijk ◽

Ji-Yun Kim ◽

Raymond Brandt ◽

Peter N. Devreotes ◽

Pauline Schaap

Keyword(s):

Gene Expression ◽

Cell Fate ◽

Dictyostelium Discoideum ◽

Developmental Regulation ◽

Mutant Cell ◽

Gene Induction ◽

Specific Gene ◽

Wild Type ◽

Animal Development ◽

Camp Stimulation

ABSTRACT Serpentine receptors such as smoothened and frizzled play important roles in cell fate determination during animal development. InDictyostelium discoideum, four serpentine cyclic AMP (cAMP) receptors (cARs) regulate expression of multiple classes of developmental genes. To understand their function, it is essential to know whether each cAR is coupled to a specific gene regulatory pathway or whether specificity results from the different developmental regulation of individual cARs. To distinguish between these possibilities, we measured gene induction in car1 car3 double mutant cell lines that express equal levels of either cAR1, cAR2, or cAR3 under a constitutive promoter. We found that all cARs efficiently mediate both aggregative gene induction by cAMP pulses and induction of postaggregative and prespore genes by persistent cAMP stimulation. Two exceptions to this functional promiscuity were observed. (i) Only cAR1 can mediate adenosine inhibition of cAMP-induced prespore gene expression, a phenomenon that was found earlier in wild-type cells. cAR1’s mediation of adenosine inhibition suggests that cAR1 normally mediates prespore gene induction. (ii) Only cAR2 allows entry into the prestalk pathway. Prestalk gene expression is induced by differentiation-inducing factor (DIF) but only after cells have been prestimulated with cAMP. We found that DIF-induced prestalk gene expression is 10 times higher in constitutive cAR2 expressors than in constitutive cAR1 or cAR3 expressors (which still have endogenous cAR2), suggesting that cAR2 mediates induction of DIF competence. Since in wild-type slugs cAR2 is expressed only in anterior cells, this could explain the so far puzzling observations that prestalk cells differentiate at the anterior region but that DIF levels are actually higher at the posterior region. After the initial induction of DIF competence, cAMP becomes a repressor of prestalk gene expression. This function can again be mediated by cAR1, cAR2, and cAR3.

Download Full-text

Peer Review #1 of "Using laser micro-dissection and qRT-PCR to analyze cell type-specific gene expression in Norway spruce phloem (v0.2)"

10.7287/peerj.362v0.2/reviews/1 ◽

2014 ◽

Author(s):

JG Whitehill

Keyword(s):

Gene Expression ◽

Peer Review ◽

Norway Spruce ◽

Specific Gene ◽

Cell Type ◽

Specific Gene Expression ◽

Qrt Pcr ◽

Cell Type Specific

Download Full-text

Genetic influences on cell type specific gene expression and splicing during neurogenesis elucidate regulatory mechanisms of brain traits

10.1101/2020.10.21.349019 ◽

2020 ◽

Author(s):

Nil Aygün ◽

Angela L. Elwell ◽

Dan Liang ◽

Michael J. Lafferty ◽

Kerry E. Cheek ◽

...

Keyword(s):

Gene Expression ◽

Regulatory Elements ◽

Regulatory Mechanisms ◽

Specific Gene ◽

Cell Type ◽

Specific Expression ◽

Risk Variants ◽

Allele Specific ◽

Cell Type Specific ◽

Regulatory Effects

SummaryInterpretation of the function of non-coding risk loci for neuropsychiatric disorders and brain-relevant traits via gene expression and alternative splicing is mainly performed in bulk post-mortem adult tissue. However, genetic risk loci are enriched in regulatory elements of cells present during neocortical differentiation, and regulatory effects of risk variants may be masked by heterogeneity in bulk tissue. Here, we map e/sQTLs and allele specific expression in primary human neural progenitors (n=85) and their sorted neuronal progeny (n=74). Using colocalization and TWAS, we uncover cell-type specific regulatory mechanisms underlying risk for these traits.

Download Full-text