Decoding the Regulatory Logic of the Drosophila Male Stem Cell System
Srividya Tamirisa,
Fani Papagiannouli,
Eugen Rempel,
Olga Ermakova,
Nils Trost,
Jun Zhou,
Juliane Mundorf,
Samantha Brunel,
Naima Ruhland,
Michael Boutros,
Jan U. Lohmann,
Ingrid Lohmann
Affiliations
Srividya Tamirisa
Centre for Organismal Studies (COS) Heidelberg, Heidelberg University, 69120 Heidelberg, Germany
Fani Papagiannouli
Centre for Organismal Studies (COS) Heidelberg, Heidelberg University, 69120 Heidelberg, Germany; Department of Developmental Biology, Beckman Center, Stanford University School of Medicine, Stanford, CA 94305-5329, USA
Eugen Rempel
Centre for Organismal Studies (COS) Heidelberg, Heidelberg University, 69120 Heidelberg, Germany
Olga Ermakova
Centre for Organismal Studies (COS) Heidelberg, Heidelberg University, 69120 Heidelberg, Germany
Nils Trost
Centre for Organismal Studies (COS) Heidelberg, Heidelberg University, 69120 Heidelberg, Germany
Jun Zhou
Division of Signaling and Functional Genomics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Department of Cell and Molecular Biology, University of Heidelberg, 69120 Heidelberg, Germany
Juliane Mundorf
Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany
Samantha Brunel
Institut Jacques Monod, University Paris-Diderot, 75205 Paris, France
Naima Ruhland
Centre for Organismal Studies (COS) Heidelberg, Heidelberg University, 69120 Heidelberg, Germany
Michael Boutros
Division of Signaling and Functional Genomics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Department of Cell and Molecular Biology, University of Heidelberg, 69120 Heidelberg, Germany
Jan U. Lohmann
Centre for Organismal Studies (COS) Heidelberg, Heidelberg University, 69120 Heidelberg, Germany
Ingrid Lohmann
Centre for Organismal Studies (COS) Heidelberg, Heidelberg University, 69120 Heidelberg, Germany; Corresponding author
Summary: The niche critically controls stem cell behavior, but its regulatory input at the whole-genome level is poorly understood. We elucidated transcriptional programs of the somatic and germline lineages in the Drosophila testis and genome-wide binding profiles of Zfh-1 and Abd-A expressed in somatic support cells and crucial for fate acquisition of both cell lineages. We identified key roles of nucleoporins and V-ATPase proton pumps and demonstrate their importance in controlling germline development from the support side. To make our dataset publicly available, we generated an interactive analysis tool, which uncovered conserved core genes of adult stem cells across species boundaries. We tested the functional relevance of these genes in the Drosophila testis and intestine and found a high frequency of stem cell defects. In summary, our dataset and interactive platform represent versatile tools for identifying gene networks active in diverse stem cell types. : Tamirisa et al. performed genome-wide profiling of the Drosophila testis to identify stem cell regulators. Comparative analysis using other stem cell systems revealed common and specific stem cell factors. They show that V-ATPase proton pumps and nucleoporins play critical roles in stem cell regulation of the testis. Keywords: Drosophila testis, somatic support cells, homeodomain transcription factors, DamID, targeted DamID, abd-A, zfh-1, stem cells, nucleoporins, V-ATPases