LGR6 marks nephron progenitor cells
van Ineveld, Ravian L.; Margaritis, Thanasis; Kooiman, Berend A.P.; Groenveld, Femke; Ariese, Hendrikus C.R.; Lijnzaad, Philip; Johnson, Hannah R.; Korving, Jeroen; Wehrens, Ellen J.; Holstege, Frank; van Rheenen, Jacco; Drost, Jarno; Rios, Anne C.; Bos, Frank L.
(2021) Developmental Dynamics, volume 250, issue 11, pp. 1568 - 1583
(Article)
Abstract
Background: Nephron progenitor cells (NPCs) undergo a stepwise process to generate all mature nephron structures. Mesenchymal to epithelial transition (MET) is considered a multistep process of NPC differentiation to ensure progressive establishment of new nephrons. However, despite this important role, to date, no marker for NPCs undergoing MET in the
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nephron exists. Results: Here, we identify LGR6 as a NPC marker, expressed in very early cap mesenchyme, pre-tubular aggregates, renal vesicles, and in segments of S-shaped bodies, following the trajectory of MET. By using a lineage tracing approach in embryonic explants in combination with confocal imaging and single-cell RNA sequencing, we provide evidence for the multiple fates of LGR6+ cells during embryonic nephrogenesis. Moreover, by using long-term in vivo lineage tracing, we show that postnatal LGR6+ cells are capable of generating the multiple lineages of the nephrons. Conclusions: Given the profound early mesenchymal expression and MET signature of LGR6+ cells, together with the lineage tracing of mesenchymal LGR6+ cells, we conclude that LGR6+ cells contribute to all nephrogenic segments by undergoing MET. LGR6+ cells can therefore be considered an early committed NPC population during embryonic and postnatal nephrogenesis with potential regenerative capability.
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Keywords: 3D imaging, fate, LGR6, lineage tracing, mesenchymal to epithelial transition, nephron progenitor cells, Developmental Biology, Journal Article
ISSN: 1058-8388
Publisher: Wiley-Liss Inc.
Note: Funding Information: We like to thank the Princess Máxima Center Single Cell Genomics, Princess Máxima Imaging Center and the Hubrecht Institute single cell sequencing and FACS facilities. We thank Utrecht Sequencing Facility for providing sequencing service and data. Utrecht Sequencing Facility is subsidized by the University Medical Center Utrecht, Hubrecht Institute, Utrecht University and The Netherlands X‐omics Initiative (NWO project 184.034.019). This work was financially supported by the Princess Máxima Center for Pediatric Oncology. FLB was supported by the Dutch Cancer Society (KWF) fellowship (ID# 6660). ACR was awarded the St. Baldrick's Robert J. Arceci International Innovation award and is supported by an ERC‐starting grant 2019, project 804412. EJW is supported by Cancer GenomiCs (CGC). TM, PL and FH were supported by European Research Council (ERC) Advanced Grant [671174]; JvR was supported by the European Research Council Grant CANCER‐RECURRENCE 648804, the CancerGenomics.nl (Netherlands Organization for Scientific Research) program and the Doctor Josef Steiner Foundation. Funding Information: We like to thank the Princess M?xima Center Single Cell Genomics, Princess M?xima Imaging Center and the Hubrecht Institute single cell sequencing and FACS facilities. We thank Utrecht Sequencing Facility for providing sequencing service and data. Utrecht Sequencing Facility is subsidized by the University Medical Center Utrecht, Hubrecht Institute, Utrecht University and The Netherlands X-omics Initiative (NWO project 184.034.019). This work was financially supported by the Princess M?xima Center for Pediatric Oncology. FLB was supported by the Dutch Cancer Society (KWF) fellowship (ID# 6660). ACR was awarded the St. Baldrick's Robert J. Arceci International Innovation award and is supported by an ERC-starting grant 2019, project 804412. EJW is supported by Cancer GenomiCs (CGC). TM, PL and FH were supported by European Research Council (ERC) Advanced Grant [671174]; JvR was supported by the European Research Council Grant CANCER-RECURRENCE 648804, the CancerGenomics.nl (Netherlands Organization for Scientific Research) program and the Doctor Josef Steiner Foundation. Funding Information: Cancer Genomics Centre; European Research Council, Grant/Award Number: 648804; European Research Council advanced, Grant/Award Number: 671174; European Research Council starting grant, Grant/Award Number: 804412; KWF Kankerbestrijding, Grant/Award Number: 6660 Funding information Publisher Copyright: © 2021 The Authors. Developmental Dynamics published by Wiley Periodicals LLC on behalf of American Association of Anatomists.
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