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Zhou Z, Shao G, Shen Y, He F, Tu X, Ji J, Ao J, Chen X. Extreme-Phenotype Genome-Wide Association Analysis for Growth Traits in Spotted Sea Bass ( Lateolabrax maculatus) Using Whole-Genome Resequencing. Animals (Basel) 2024; 14:2995. [PMID: 39457925 PMCID: PMC11503831 DOI: 10.3390/ani14202995] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Revised: 10/09/2024] [Accepted: 10/15/2024] [Indexed: 10/28/2024] Open
Abstract
Spotted sea bass (Lateolabrax maculatus) is an important marine economic fish in China, ranking third in annual production among marine fish. However, a declined growth rate caused by germplasm degradation has severely increased production costs and reduced economic benefits. There is an urgent need to develop the fast-growing varieties of L. maculatus and elucidate the genetic mechanisms underlying growth traits. Here, whole-genome resequencing technology combined with extreme phenotype genome-wide association analysis (XP-GWAS) was used to identify candidate markers and genes associated with growth traits in L. maculatus. Two groups of L. maculatus, consisting of 100 fast-growing and 100 slow-growing individuals with significant differences in body weight, body length, and carcass weight, underwent whole-genome resequencing. A total of 4,528,936 high-quality single nucleotide polymorphisms (SNPs) were used for XP-GWAS. These SNPs were evenly distributed across all chromosomes without large gaps, and the average distance between SNPs was only 175.8 bp. XP-GWAS based on the Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (Blink) and Fixed and random model Circulating Probability Unification (FarmCPU) identified 50 growth-related markers, of which 17 were related to body length, 19 to body weight, and 23 to carcass weight. The highest phenotypic variance explained (PVE) reached 15.82%. Furthermore, significant differences were observed in body weight, body length, and carcass weight among individuals with different genotypes. For example, there were highly significant differences in body weight among individuals with different genotypes for four SNPs located on chromosome 16: chr16:13133726, chr16:13209537, chr16:14468078, and chr16:18537358. Additionally, 47 growth-associated genes were annotated. These genes are mainly related to the metabolism of energy, glucose, and lipids and the development of musculoskeletal and nervous systems, which may regulate the growth of L. maculatus. Our study identified growth-related markers and candidate genes, which will help to develop the fast-growing varieties of L. maculatus through marker-assisted breeding and elucidate the genetic mechanisms underlying the growth traits.
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Affiliation(s)
- Zhaolong Zhou
- Fuzhou Institute of Oceanography, State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, College of Marine Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China; (Z.Z.); (G.S.); (Y.S.); (F.H.); (X.T.); (J.J.)
| | - Guangming Shao
- Fuzhou Institute of Oceanography, State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, College of Marine Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China; (Z.Z.); (G.S.); (Y.S.); (F.H.); (X.T.); (J.J.)
| | - Yibo Shen
- Fuzhou Institute of Oceanography, State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, College of Marine Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China; (Z.Z.); (G.S.); (Y.S.); (F.H.); (X.T.); (J.J.)
| | - Fengjiao He
- Fuzhou Institute of Oceanography, State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, College of Marine Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China; (Z.Z.); (G.S.); (Y.S.); (F.H.); (X.T.); (J.J.)
| | - Xiaomei Tu
- Fuzhou Institute of Oceanography, State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, College of Marine Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China; (Z.Z.); (G.S.); (Y.S.); (F.H.); (X.T.); (J.J.)
| | - Jiawen Ji
- Fuzhou Institute of Oceanography, State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, College of Marine Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China; (Z.Z.); (G.S.); (Y.S.); (F.H.); (X.T.); (J.J.)
| | - Jingqun Ao
- Fuzhou Institute of Oceanography, State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, College of Marine Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China; (Z.Z.); (G.S.); (Y.S.); (F.H.); (X.T.); (J.J.)
| | - Xinhua Chen
- Fuzhou Institute of Oceanography, State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, College of Marine Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China; (Z.Z.); (G.S.); (Y.S.); (F.H.); (X.T.); (J.J.)
- Southern Marine Science and Engineering Guangdong Laboratory, Zhuhai 519000, China
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Pantaleo E, Monaco A, Amoroso N, Lombardi A, Bellantuono L, Urso D, Lo Giudice C, Picardi E, Tafuri B, Nigro S, Pesole G, Tangaro S, Logroscino G, Bellotti R. A Machine Learning Approach to Parkinson’s Disease Blood Transcriptomics. Genes (Basel) 2022; 13:genes13050727. [PMID: 35627112 PMCID: PMC9141063 DOI: 10.3390/genes13050727] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Revised: 04/16/2022] [Accepted: 04/18/2022] [Indexed: 12/23/2022] Open
Abstract
The increased incidence and the significant health burden associated with Parkinson’s disease (PD) have stimulated substantial research efforts towards the identification of effective treatments and diagnostic procedures. Despite technological advancements, a cure is still not available and PD is often diagnosed a long time after onset when irreversible damage has already occurred. Blood transcriptomics represents a potentially disruptive technology for the early diagnosis of PD. We used transcriptome data from the PPMI study, a large cohort study with early PD subjects and age matched controls (HC), to perform the classification of PD vs. HC in around 550 samples. Using a nested feature selection procedure based on Random Forests and XGBoost we reached an AUC of 72% and found 493 candidate genes. We further discussed the importance of the selected genes through a functional analysis based on GOs and KEGG pathways.
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Affiliation(s)
- Ester Pantaleo
- Istituto Nazionale di Fisica Nucleare (INFN), Sezione di Bari, Via A. Orabona 4, 70125 Bari, Italy; (E.P.); (A.M.); (N.A.); (L.B.); (S.T.); (R.B.)
- Dipartimento di Scienze Mediche di Base, Neuroscienze e Organi di Senso, Università degli Studi di Bari Aldo Moro, Piazza G. Cesare 11, 70124 Bari, Italy;
- Dipartimento Interateneo di Fisica M. Merlin, Università degli Studi di Bari Aldo Moro, Via G. Amendola 173, 70125 Bari, Italy
| | - Alfonso Monaco
- Istituto Nazionale di Fisica Nucleare (INFN), Sezione di Bari, Via A. Orabona 4, 70125 Bari, Italy; (E.P.); (A.M.); (N.A.); (L.B.); (S.T.); (R.B.)
| | - Nicola Amoroso
- Istituto Nazionale di Fisica Nucleare (INFN), Sezione di Bari, Via A. Orabona 4, 70125 Bari, Italy; (E.P.); (A.M.); (N.A.); (L.B.); (S.T.); (R.B.)
- Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari Aldo Moro, Via A. Orabona 4, 70125 Bari, Italy
| | - Angela Lombardi
- Istituto Nazionale di Fisica Nucleare (INFN), Sezione di Bari, Via A. Orabona 4, 70125 Bari, Italy; (E.P.); (A.M.); (N.A.); (L.B.); (S.T.); (R.B.)
- Dipartimento Interateneo di Fisica M. Merlin, Università degli Studi di Bari Aldo Moro, Via G. Amendola 173, 70125 Bari, Italy
- Correspondence:
| | - Loredana Bellantuono
- Istituto Nazionale di Fisica Nucleare (INFN), Sezione di Bari, Via A. Orabona 4, 70125 Bari, Italy; (E.P.); (A.M.); (N.A.); (L.B.); (S.T.); (R.B.)
- Dipartimento di Scienze Mediche di Base, Neuroscienze e Organi di Senso, Università degli Studi di Bari Aldo Moro, Piazza G. Cesare 11, 70124 Bari, Italy;
| | - Daniele Urso
- Centro per le Malattie Neurodegenerative e l’Invecchiamento Cerebrale, Dipartimento di Ricerca Clinica in Neurologia, Università degli Studi di Bari Aldo Moro, Pia Fondazione Cardinale G. Panico, 73039 Tricase, Italy; (D.U.); (B.T.); (S.N.)
- Institute of Psychiatry, Psychology and Neuroscience, King’s College London, De Crespigny Park, London SE5 8AF, UK
| | - Claudio Lo Giudice
- Dipartimento di Bioscienze, Biotecnologie e Biofarmaceutica, Università degli Studi di Bari Aldo Moro, Via A. Orabona 4, 70125 Bari, Italy; (C.L.G.); (E.P.); (G.P.)
| | - Ernesto Picardi
- Dipartimento di Bioscienze, Biotecnologie e Biofarmaceutica, Università degli Studi di Bari Aldo Moro, Via A. Orabona 4, 70125 Bari, Italy; (C.L.G.); (E.P.); (G.P.)
- Istituto di Biomembrane, Bioenergetica e Biotecnologie Molecolari, Consiglio Nazionale delle Ricerche, Via G. Amendola 122/O, 70126 Bari, Italy
| | - Benedetta Tafuri
- Centro per le Malattie Neurodegenerative e l’Invecchiamento Cerebrale, Dipartimento di Ricerca Clinica in Neurologia, Università degli Studi di Bari Aldo Moro, Pia Fondazione Cardinale G. Panico, 73039 Tricase, Italy; (D.U.); (B.T.); (S.N.)
| | - Salvatore Nigro
- Centro per le Malattie Neurodegenerative e l’Invecchiamento Cerebrale, Dipartimento di Ricerca Clinica in Neurologia, Università degli Studi di Bari Aldo Moro, Pia Fondazione Cardinale G. Panico, 73039 Tricase, Italy; (D.U.); (B.T.); (S.N.)
- Istituto di Nanotecnologia (NANOTEC), Consiglio Nazionale delle Ricerche, Via Monteroni, 73100 Lecce, Italy
| | - Graziano Pesole
- Dipartimento di Bioscienze, Biotecnologie e Biofarmaceutica, Università degli Studi di Bari Aldo Moro, Via A. Orabona 4, 70125 Bari, Italy; (C.L.G.); (E.P.); (G.P.)
- Istituto di Biomembrane, Bioenergetica e Biotecnologie Molecolari, Consiglio Nazionale delle Ricerche, Via G. Amendola 122/O, 70126 Bari, Italy
| | - Sabina Tangaro
- Istituto Nazionale di Fisica Nucleare (INFN), Sezione di Bari, Via A. Orabona 4, 70125 Bari, Italy; (E.P.); (A.M.); (N.A.); (L.B.); (S.T.); (R.B.)
- Dipartimento di Scienze del Suolo, della Pianta e degli Alimenti, Università degli Studi di Bari Aldo Moro, Via A. Orabona 4, 70125 Bari, Italy
| | - Giancarlo Logroscino
- Dipartimento di Scienze Mediche di Base, Neuroscienze e Organi di Senso, Università degli Studi di Bari Aldo Moro, Piazza G. Cesare 11, 70124 Bari, Italy;
- Centro per le Malattie Neurodegenerative e l’Invecchiamento Cerebrale, Dipartimento di Ricerca Clinica in Neurologia, Università degli Studi di Bari Aldo Moro, Pia Fondazione Cardinale G. Panico, 73039 Tricase, Italy; (D.U.); (B.T.); (S.N.)
| | - Roberto Bellotti
- Istituto Nazionale di Fisica Nucleare (INFN), Sezione di Bari, Via A. Orabona 4, 70125 Bari, Italy; (E.P.); (A.M.); (N.A.); (L.B.); (S.T.); (R.B.)
- Dipartimento Interateneo di Fisica M. Merlin, Università degli Studi di Bari Aldo Moro, Via G. Amendola 173, 70125 Bari, Italy
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Gayen Nee' Betal S, Urday P, Al-Kouatly HB, Solarin K, Chan JSY, Addya S, Boelig RC, Aghai ZH. COVID-19 Infection During Pregnancy Induces Differential Gene Expression in Human Cord Blood Cells From Term Neonates. Front Pediatr 2022; 10:834771. [PMID: 35547542 PMCID: PMC9084610 DOI: 10.3389/fped.2022.834771] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Accepted: 03/24/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND The COVID-19 pandemic continues worldwide with fluctuating case numbers in the United States. This pandemic has affected every segment of the population with more recent hospitalizations in the pediatric population. Vertical transmission of COVID-19 is uncommon, but reports show that there are thrombotic, vascular, and inflammatory changes in the placenta to which neonates are prenatally exposed. Individuals exposed in utero to influenza during the 1918 pandemic had increased risk for heart disease, kidney disease, diabetes, stomach disease and hypertension. Early exposure of COVID-19 during fetal life may lead to altered gene expression with potential long-term consequences. OBJECTIVE To determine if gene expression is altered in cord blood cells from term neonates who were exposed to COVID-19 during pregnancy and to identify potential gene pathways impacted by maternal COVID-19. METHODS Cord blood was collected from 16 term neonates (8 exposed to COVID-19 during pregnancy and 8 controls without exposure to COVID-19). Genome-wide gene expression screening was performed using Human Clariom S gene chips on total RNA extracted from cord blood cells. RESULTS We identified 510 differentially expressed genes (374 genes up-regulated, 136 genes down-regulated, fold change ≥1.5, p-value ≤ 0.05) in cord blood cells associated with exposure to COVID-19 during pregnancy. Ingenuity Pathway Analysis identified important canonical pathways associated with diseases such as cardiovascular disease, hematological disease, embryonic cancer and cellular development. Tox functions related to cardiotoxicity, hepatotoxicity and nephrotoxicity were also altered after exposure to COVID-19 during pregnancy. CONCLUSIONS Exposure to COVID-19 during pregnancy induces differential gene expression in cord blood cells. The differentially expressed genes may potentially contribute to cardiac, hepatic, renal and immunological disorders in offspring exposed to COVID-19 during pregnancy. These findings lead to a further understanding of the effects of COVID-19 exposure at an early stage of life and its potential long-term consequences as well as therapeutic targets.
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Affiliation(s)
| | - Pedro Urday
- Neonatology, Thomas Jefferson University/Nemours, Philadelphia, PA, United States
| | - Huda B Al-Kouatly
- Maternal Fetal Medicine, Thomas Jefferson University, Philadelphia, PA, United States
| | - Kolawole Solarin
- Neonatology, Thomas Jefferson University/Nemours, Philadelphia, PA, United States
| | - Joanna S Y Chan
- Department of Pathology, Thomas Jefferson University, Philadelphia, PA, United States
| | - Sankar Addya
- Laboratory of Cancer Genomics, Thomas Jefferson University, Philadelphia, PA, United States
| | - Rupsa C Boelig
- Maternal Fetal Medicine, Thomas Jefferson University, Philadelphia, PA, United States
| | - Zubair H Aghai
- Neonatology, Thomas Jefferson University/Nemours, Philadelphia, PA, United States
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Zhytnik L, Maasalu K, Reimann E, Märtson A, Kõks S. RNA sequencing analysis reveals increased expression of interferon signaling genes and dysregulation of bone metabolism affecting pathways in the whole blood of patients with osteogenesis imperfecta. BMC Med Genomics 2020; 13:177. [PMID: 33228694 PMCID: PMC7684725 DOI: 10.1186/s12920-020-00825-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Accepted: 11/15/2020] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Osteogenesis imperfecta (OI) is a rare genetic disorder in which the patients suffer from numerous fractures, skeletal deformities and bluish sclera. The disorder ranges from a mild form to severe and lethal cases. The main objective of this pilot study was to compare the blood transcriptional landscape of OI patients with COL1A1 pathogenic variants and their healthy relatives, in order to find out different gene expression and dysregulated molecular pathways in OI. METHODS We performed RNA sequencing analysis of whole blood in seven individuals affected with different OI severity and their five unaffected relatives from the three families. The data was analyzed using edgeR package of R Bioconductor. Functional profiling and pathway analysis of the identified differently expressed genes was performed with g:GOSt and MinePath web-based tools. RESULTS We identified 114 differently expressed genes. The expression of 79 genes was up-regulated, while 35 genes were down-regulated. The functional analysis identified a presence of dysregulated interferon signaling pathways (IFI27, IFITM3, RSAD12, GBP7). Additionally, the expressions of the genes related to extracellular matrix organization, Wnt signaling, vitamin D metabolism and MAPK-ERK 1/2 pathways were also altered. CONCLUSIONS The current pilot study successfully captured the differential expression of inflammation and bone metabolism pathways in OI patients. This work can contribute to future research of transcriptional bloodomics in OI. Transcriptional bloodomics has a strong potential to become a major contributor to the understanding of OI pathological mechanisms, the discovery of phenotype modifying factors, and the identification of new therapeutic targets. However, further studies in bigger cohorts of OI patients are needed to confirm the findings of the current work.
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Affiliation(s)
- Lidiia Zhytnik
- Clinic of Traumatology and Orthopedics, Tartu University Hospital, Puusepa 8, 51014, Tartu, Estonia.
| | - Katre Maasalu
- Clinic of Traumatology and Orthopedics, Tartu University Hospital, Puusepa 8, 51014, Tartu, Estonia
- Department of Traumatology and Orthopedics, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia
| | - Ene Reimann
- Estonian Genome Centre, University of Tartu, Tartu, Estonia
| | - Aare Märtson
- Clinic of Traumatology and Orthopedics, Tartu University Hospital, Puusepa 8, 51014, Tartu, Estonia
- Department of Traumatology and Orthopedics, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia
| | - Sulev Kõks
- Perron Institute for Neurological and Translational Science, QEII Medical Centre, Nedlands, WA, Australia
- Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Murdoch, WA, Australia
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Rap1GAP inhibits tumor progression in endometrial cancer. Biochem Biophys Res Commun 2017; 485:476-483. [PMID: 28196746 DOI: 10.1016/j.bbrc.2017.02.044] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2017] [Accepted: 02/07/2017] [Indexed: 01/04/2023]
Abstract
OBJECTIVE Endometrioid adenocarcinoma (EAC) is a common endometrial cancer with recent dramatic increases in incidence. Previous findings indicate that Rap1GAP acts as a tumor suppressor inhibiting Ras superfamily protein Rap1 in multiple aggressive carcinomas; however, Rap1GAP expression in EAC has not been investigated. In this study, the tumor suppressing activity of Rap1GAP in EAC was explored. METHODS EAC cell lines were used to examine Rap1GAP levels by real-time RT-PCR and western blotting and the effects of Rap1GAP on cancer cell invasion and migration. Rap1GAP expression was analyzed by immunohistochemical staining for Rap1GAP, E-cadherin in surgically resected tumors of 114 EAC patients scored according to EAC differentiation grade. Prognostic variables such as age, stage, grade, tumor size, and immunostaining for Rap1GAP, E-cadherin were evaluated using Cox regression multivariate analysis. RESULTS Low Rap1GAP expression was detected in poorly differentiated EAC cells. Rap1GAP deficiency significantly accelerated while Rap1 deficiency decreased cancer cell migration and invasion. Patients with higher Rap1GAP, E-cadherin, and especially combined Rap1GAP/E-cadherin levels had better overall survival than EAC patients with no or weak expression. In addition, Rap1GAP expression was an independent prognostic factor in EAC. CONCLUSIONS Inhibition of Rap1GAP expression increases EAC cell migration and invasion through upregulation of Rap1. Low expression of Rap1GAP correlates with poor EAC differentiation. Our findings suggest that Rap1GAP is an important tumor suppressor with high prognostic value in EAC.
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Dorn DC, Dorn A. Stem cell autotomy and niche interaction in different systems. World J Stem Cells 2015; 7:922-944. [PMID: 26240680 PMCID: PMC4515436 DOI: 10.4252/wjsc.v7.i6.922] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2014] [Accepted: 05/27/2015] [Indexed: 02/06/2023] Open
Abstract
The best known cases of cell autotomy are the formation of erythrocytes and thrombocytes (platelets) from progenitor cells that reside in special niches. Recently, autotomy of stem cells and its enigmatic interaction with the niche has been reported from male germline stem cells (GSCs) in several insect species. First described in lepidopterans, the silkmoth, followed by the gipsy moth and consecutively in hemipterans, foremost the milkweed bug. In both, moths and the milkweed bug, GSCs form finger-like projections toward the niche, the apical cells (homologs of the hub cells in Drosophila). Whereas in the milkweed bug the projection terminals remain at the surface of the niche cells, in the gipsy moth they protrude deeply into the singular niche cell. In both cases, the projections undergo serial retrograde fragmentation with progressing signs of autophagy. In the gipsy moth, the autotomized vesicles are phagocytized and digested by the niche cell. In the milkweed bug the autotomized vesicles accumulate at the niche surface and disintegrate. Autotomy and sprouting of new projections appears to occur continuously. The significance of the GSC-niche interactions, however, remains enigmatic. Our concept on the signaling relationship between stem cell-niche in general and GSC and niche (hub cells and cyst stem cells) in particular has been greatly shaped by Drosophila melanogaster. In comparing the interactions of GSCs with their niche in Drosophila with those in species exhibiting GSC autotomy it is obvious that additional or alternative modes of stem cell-niche communication exist. Thus, essential signaling pathways, including niche-stem cell adhesion (E-cadherin) and the direction of asymmetrical GSC division - as they were found in Drosophila - can hardly be translated into the systems where GSC autotomy was reported. It is shown here that the serial autotomy of GSC projections shows remarkable similarities with Wallerian axonal destruction, developmental axon pruning and dying-back degeneration in neurodegenerative diseases. Especially the hypothesis of an existing evolutionary conserved “autodestruction program” in axons that might also be active in GSC projections appears attractive. Investigations on the underlying signaling pathways have to be carried out. There are two other well known cases of programmed cell autotomy: the enucleation of erythroblasts in the process of erythrocyte maturation and the segregation of thousands of thrombocytes (platelets) from one megakaryocyte. Both progenitor cell types - erythroblasts and megakaryocytes - are associated with a niche in the bone marrow, erythroblasts with a macrophage, which they surround, and the megakaryocytes with the endothelial cells of sinusoids and their extracellular matrix. Although the regulatory mechanisms may be specific in each case, there is one aspect that connects all described processes of programmed cell autotomy and neuronal autodestruction: apoptotic pathways play always a prominent role. Studies on the role of male GSC autotomy in stem cell-niche interaction have just started but are expected to reveal hitherto unknown ways of signal exchange. Spermatogenesis in mammals advance our understanding of insect spermatogenesis. Mammal and insect spermatogenesis share some broad principles, but a comparison of the signaling pathways is difficult. We have intimate knowledge from Drosophila, but of almost no other insect, and we have only limited knowledge from mammals. The discovery of stem cell autotomy as part of the interaction with the niche promises new general insights into the complicated stem cell-niche interdependence.
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