Identification of a Zeb1 expressing basal stem cell subpopulation in the prostate
Authors: Huifang Zhao
Liancheng Fan
Helen He Zhu
Haibo Xu
Xue Wang
Chaping Cheng
Dongdong Wu
Yu Shu
Yuman He
Xiaoxia Li
Yaru Sheng
Wei Xue
Wei-Qiang Gao
Zhongzhong Ji
Baijun Dong
Chee Wai Chua
Jinming Wang
Journal: Nature communications (2020)
Discipline: Multidisciplinary
Keywords: Basal cell compartment; stem cells; Zeb1; epithelial-to-mesenchymal transition (EMT); prostate basal stem cells (PBSCs)
Affiliations: State Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Stem Cell Research Center, Department of Urology, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200127, China., Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030, China., State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Sciences, Kunming, 650223, China., University of Chinese Academy of Sciences, Beijing, 100049, China., Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China., State Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Stem Cell Research Center, Department of Urology, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200127, China. ., Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030, China. ., Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. .

Abstract:  The basal cell compartment in many epithelial tissues is generally believed to serve as an important pool of stem cells. However, basal cells are heterogenous and the stem cell subpopulation within basal cells is not well elucidated. Here we uncover that the core epithelial-to-mesenchymal transition (EMT) inducer Zeb1 is expressed in a prostate basal cell subpopulation. The Zeb1+ prostate epithelial cells are multipotent prostate basal stem cells (PBSCs) that can self-renew and generate functional prostatic glandular structures at the single-cell level. Genetic ablation studies reveal an indispensable role for Zeb1 in prostate basal cell development. Utilizing unbiased single-cell transcriptomic analysis of over 9000 mouse prostate basal cells, we confirm the existence of the Zeb1+ basal cell subset. Moreover, Zeb1+ epithelial cells can be detected in mouse and human prostate tumors. Identification of the PBSC and its transcriptome profile is crucial to advance our understanding of prostate development and tumorigenesis. 

Retracted: No

PubPeer comments:
 Copy pasted from https: doi.org 10.1016 j.ijid.2021.02.097 :  LETTER TO THE EDITOR | VOLUME 105, P 606-607, APRIL 01, 2021, Misconceptions and misinformation about bats and viruses, viruses Sebastien J. Puechmaille, Meriadeg Ar Gouilh, Dina Dechmann, Brock Fenton, Cullen Geiselman, Rodrigo Medellin, Russell Mittermeier, Paul Racey, DeeAnn M. Reeder, Juliane Schaer, Amanda Vicente-Santos, Wes Sechrest, Luis Vu00edquez-R and Natalie Weber, Published: March 01, 2021. To the Editor, In recent decades, the role of bats, order Chiroptera, as potential reservoirs for several zoonotic viruses has received considerable attention. This has dramatically increased since the emergence of the SARS-CoV-2 virus causing COVID-19, resulting in numerous recent reviews. Unfortunately, some of these contain outdated or false statements and incomplete treatments and or misinterpretations of the published literature, such as Bonilla-Aldana et al., 2021. We herein report the main problems with their paper and illustrate our point with examples; a complete enumeration would be too extensive. First, we submitted two independent Correspondences to the Journal, on 28 09 2020 and 30 09 2020, asking for a retraction of the accepted and u201cin Press, Pre-proofu201d paper published online on 20 08 2020. That paper contained multiple critical errors and misrepresentations related to bat taxonomy, ecology, and physiology, and the linkages between bats and specific viruses. Around 25 11 2020, the u201cIn pressu201d paper was substantially amended and expanded, however, these changes only fixed a minority of the reported problems and even added new ones, including several baffling sentences (e.g., u201cBats are mammals, bone marrow and B cellsu201d). Second, Bonilla-Aldana et al. wrote a confusing misleading section about bat nomenclature. As clearly expressed via a disclaimer on the NCBI-NIH website, the system used in their Taxonomy Browser is u201cnot an authoritative source for nomenclature or classificationu201d, and the NCBI-NIH advise to u201cconsult the relevant scientific literature for the most reliable informationu201d. Twenty years ago, molecular data clearly rejected the subdivision of the Order Chiroptera into u2018Megachiropterau2019 (for which the authors created a new term in Table 2 and Fig. 1: the u2018Macrochiropterau2019) and u2018Microchiropterau2019 (Jebb et al., 2020, Teeling et al., 2000). The 1432 currently known bat species are subdivided into Yinpterochiroptera and Yangochiroptera; several species formerly grouped with u2018Microchiropterau2019 are more closely related to u2018megabatsu2019 than to other u2018microbatsu2019. Using this established classification is critical to understanding bat evolution, including batsu2019 association with viruses (Foley et al., 2015, Teeling et al., 2018). Also, Bonilla-Aldana et al. include several misspelled or outdated genera species names (e.g., Sturnina instead of Sturnira, Dhiphylla instead of Diphylla, Hipposideros commersoni instead of Macronycteris commersonii, Hemiderma instead of Carollia, Artibeus turpis instead of Artibeus Dermanura phaeotis). Also, the species Epomophorus gambianus occurs in Africa and not in Asia, as reported in their Figure 1. Third, Bonilla-Aldana et al. pack vague, incompatible, inaccurate, and incorrect statements in their overview of the biology and ecology of bats. For example, contrary to what they wrote, hematophagous (=feeding on blood) bats do not u201ccapture birds and mammalsu201d that are tens to several thousands of times heavier than them. They feed on these target animals by drinking blood from an incision on their skin. u2018Megabatsu2019 do not weigh on average 1 kg; only the largest ones exceed 1 kg (Altringham, 2011). In our previous Correspondence, we wrote that u201cu2018Microbatsu2019, formerly representing u2018Microchiroptera,u2019 do not eat mainly flowers and fruit but insectsu201d, a sentence that has been pasted in the paper, but without deleting the original sentence saying: u201cTheir size ranges from 4 to 16 cm and feed mostly on flowers and fruitu201d, which is both confusing and contradictory. Also, it is unclear if the authors are referring to the wingspan size range, as they did before for the u2018Megabatsu2019; if so, the statement is clearly wrong. Fourth and most importantly, we found many problems with their review of the viruses listed as transmitted from bats to other mammals, including humans. It is concerning that despite affirming that they conducted a comprehensive review (as the authors claim in the online u201chighlightsu201d of the paper), the bulk of their data (summarized in Tables 1, 2, and 3) are lacking any references, making it impossible to understand how the authors came up with an identified reservoir host, their modes of transmission and related factors. For several of these viruses, transmission chains remain unknown (e.g., Ebola, Influenza A, togaviruses). Bonilla-Aldana et al. should have noted that some of the claims they made have been rejected by others (Dengue; Vicente-Santos et al., 2017). The authors also make incorrect claims, such as u201cRabies transmission primarily occurs via direct bites or scratches from infected bats; secondary transmissions in humans take place through contact with infected petsu201d. According to the WHO, 99% of human cases of rabies are transmitted by domestic dogs. In short, this tendentious review is far from comprehensive or accurate. The authors appear to have consulted a random subset of publications. The selection includes contradictory statements. The assignment of hosts and viruses is not consistent (e.g., for Ebola, several fruit bats in Table 1, and Myotis in the text; for Coronaviruses, Dobsonia moluccensis in Table 2, 12 different bat species in Table 1 [including Dobsonia moluccensis], bats and rodents in the text). Anyone presenting a review of a taxonomic group and its diseases should include experts in the taxonomic groupu2019s biology and ecology, as well as experts in the diseases reviewed. Otherwise, the review will only create confusion and misconceptions. , 
 https: www.sciencedirect.com science article pii S120197122100182X Letter to the Editor Reply to u201cMisconceptions and misinformation about bats and virusesu201d D. Katterine Bonilla-Aldana,1 S. Daniela Jimenez-Diaz,1 J. Sebastian Arango-Duque,2 Mateo Aguirre-Florez,3 Graciela J. Balbin-Ramon,4 Alberto Paniz-Mondolfi,5,6,7 Jose Antonio Suu00e1rez,8 Monica R. Pachar,9 Luis A. Perez-Garcia,10 Lourdes A. Delgado-Noguera,10 Manuel Antonio Sierra,11 Fausto Muu00f1oz-Lara,12,13 Lysien I. Zambrano,14 Alfonso J. Rodriguez-Morales.15,* t 1Semillero de Investigaciu00f3n en Zoonosis (SIZOO), Grupo de Investigaciu00f3n BIOECOS, Fundaciu00f3n Universitaria Autu00f3noma de las Amu00e9ricas, Sede Pereira, Pereira, Risaralda, Colombia. 2Unidad Central del Valle del Cauca, Tulua, Valle del Cauca, Colombia. 3Universidad Tecnolu00f3gica de Pereira, Pereira, Risaralda, Colombia. 4Hospital de Emergencias Jose Casimiro Ulloa, Lima, Peru. 5Laboratory of Medical Microbiology, Department of Pathology, Molecular and Cell-based Medicine, The Mount Sinai Hospital-Icahn School of Medicine at Mount Sinai, New York, USA. 6Laboratorio de Seu00f1alizaciu00f3n Celular y Bioquu00edmica de Paru00e1sitos, Instituto de Estudios Avanzados (IDEA), Caracas, Caracas, Venezuela. 7Academia Nacional de Medicina, Caracas, Venezuela. 8Investigador SNI Senacyt Panamu00e1, Clinical Research Deparment, Instituto Conmemorativo Gorgas de Estudios de la Salud, Panamu00e1 City, Panama. 9Medicine Department - Infectious Diseases Service, Hospital Santo Tomas, Panama City, Panama. 10Instituto de Investigaciones Biomu00e9dicas IDB Incubadora Venezolana de la Ciencia, Cabudare, Edo. Lara, Venezuela. 11Facultad de Ciencias Mu00e9dicas, Universidad Nacional Autu00f3noma de Honduras (UNAH), Tegucigalpa, Honduras. 12Departamento de Medicina Interna, Hospital Escuela, Tegucigalpa, Honduras. 13Departamento de Medicina Interna, Facultad de Ciencias Mu00e9dicas, Universidad Nacional Autu00f3noma de Honduras (UNAH), Tegucigalpa, Honduras. 14Departments of Physiological and Morphological Sciences, School of Medical Sciences, Universidad Nacional Autu00f3noma de Honduras (UNAH), Tegucigalpa, Honduras. 15Grupo de Investigaciu00f3n Biomedicina, Faculty of Medicine, Fundaciu00f3n Universitaria Autu00f3noma de las Amu00e9ricas, Pereira, Risaralda, Colombia. *Corresponding Author. Email: alfonso.rodriguez@uam.edu.co. Grupo de Investigaciu00f3n Biomedicina, Faculty of Medicine, Fundaciu00f3n Universitaria Autu00f3noma de las Amu00e9ricas, Pereira, Risaralda, Colombia. In first place we welcome the letter of Puechmaille et al, about our review article (Bonilla-Aldana et al, 2020). We agree that bats have received considerable attention as potential reservoirs of several zoonotic viruses, which is the main focus of our article. Nevertheless, although highlighted for the SARS-CoV-2 COVID-19 situation, this emerging coronavirus has been not the only concern over the last decades regarding bats. We strongly disagree in the appreciation of Puechmaille et al, regarding our article. We include information based on multiple sources, we cited so far 94 articles from multiple journals, multiple authors and countries, related to studies and other reviews of different nature, which is usually above the number of included references for a narrative review, as our article is. We developed a review article, not a u201cstudyu201d as incorrectly Puechmaille et al stated. Secondly, this is a narrative review (not a systematic review). Certainly, we were informed about the correspondence you sent to the journal, before the current letter, asking u201cretractionu201d of our review article, which was clearly dismissed in terms of such request, by the journal and the editors. As the letter was directed to a preproof version of our manuscript (an article in press, not a definitive version, that still may go for enhancements and where the text could still change), we considered many of the suggestions of the initial letter, and as Puechmaille et al, clearly stated now also, we substantially amended and expanded our article. We included references suggested. We accept their comments for the article improvement, similar to what occurs during peer-review process, and we cited many of the references suggested by Puechmaille et al, in addition to other new references cited. Specially with SARS-CoV-2 COVID-19, over the last months, new significant references have been published, and this is not only a controversial topic, as is derived for the concern of Puechmaille et al, but rapidly changing, as multiple studies on it, are under developing (Motayo et al., 2020, Streicker and Gilbert, 2020, Schlottau et al., 2020, Wacharapluesadee et al., 2021, Kia et al., 2020). We acknowledge some typos present in the final version, inadvertently uncorrected during proofs stage. Regarding nomenclature, we have to repeat that the main focus of our review is on the viral infectious diseases that have been reported in bats in different sources, cited, not on taxonomy. We clearly included the Yinpterochiroptera and Yangochiroptera subdivision. In addition, we mentioned the other two. Those additional classifications exist, no matter consensus or agreement on their use or reference by Puechmaille et al. Although for biologists, bat evolution, ecology and taxonomy is interesting, that, again, is not the focus of our review article. Viral infectious agents present or reported in bats are, doubtless, a matter of concern for public health, where we agree more studies are certainly needed over time. Our article is not a systematic review, is a narrative review on the available information in cited papers. We agree that for some of the viruses, as we clearly stated in the article, still their role needs to be fully confirmed and understood. Specially transmission chains still need more studies. We wanted to call and raise the awareness of the potential viral threats that may came from bats, some of them, clearly undeniable, as is the case of rabies. Puechmaille et al misinterpreted the section on this virus. Clearly in urban areas human cases of rabies are fundamentally related to domestic animals as dogs, but in wild natural habitats, wild animals, such as bats are related and involved in the transmission of rabies in other animals (livestock) and humans. As we clearly stated, we provided an updated narrative review, showing information on a wide range of viral pathogens that have been reported in bats. Specific articles focused on particular pathogens have been also published and are available. More studies certainly are needed to clarify specifically in detail, the relative importance, transmission ways and impact of viral pathogens that may be present, including not only those already reported, but new emerging pathogens that deserve more studies by multidisciplinary teams of researchers, collaborating in a constructive way, in pro of the global public health, giving the importance that pathogens, such as SARS-CoV-2, represent for the humankind. Finally, we do not blame the bats on the SARS-CoV-2 and other viruses epidemics and pandemics, but the impacts of the human activity on wildlife conservation, among many other anthropogenic and non-anthropogenic interplayed factors (Turcios-Casco and Cazzolla Gatti, 2020). Conflict of Interest. All authors declare no conflict of interest. Funding Source. None. Ethical Approval. Not required. References Bonilla-Aldana D.K., et al. Bats in ecosystems and their Wide spectrum of viral infectious potential threats: SARS-CoV-2 and other emerging viruses. Int J Infect Dis 2021; 102: 87-96. Kia GSN, Tao Y, Umoh JU, Kwaga JKP, Tong S. Identification of Coronaviruses, Paramyxoviruses, Reoviruses, and Rotaviruses among Bats in Nigeria. Am J Trop Med Hyg. 2021 Jan 18:tpmd190872. Motayo BO, Oluwasemowo OO, Akinduti PA. Evolutionary dynamics and geographic dispersal of beta coronaviruses in African bats. PeerJ. 2020 Nov 26;8:e10434. doi: 10.7717 peerj.10434. Schlottau K, et al. SARS-CoV-2 in fruit bats, ferrets, pigs, and chickens: an experimental transmission study. Lancet Microbe. 2020;1(5):e218-e225. doi: 10.1016 S2666-5247(20)30089-6. Streicker DG, Gilbert AT. Contextualizing bats as viral reservoirs. Science. 2020 Oct 9;370(6513):172-173. doi: 10.1126 science.abd4559. Turcios-Casco MA, Cazzolla Gatti R. Do not blame bats and pangolins! Global consequences for wildlife conservation after the SARS-CoV-2 pandemic. Biodivers Conserv. 2020 Sep 19:1-5. doi: 10.1007 s10531-020-02053-y. Wacharapluesadee S, et al. Evidence for SARS-CoV-2 related coronaviruses circulating in bats and pangolins in Southeast Asia. Nat Commun. 2021 Feb 9;12(1):972. doi: 10.1038 s41467-021-21240-1. ,