LGR6 marks nephron progenitor cells.
Autor: | van Ineveld RL; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.; Oncode Institute, Utrecht, The Netherlands., Margaritis T; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., Kooiman BAP; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., Groenveld F; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center (UMC) Utrecht, Utrecht, The Netherlands., Ariese HCR; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.; Oncode Institute, Utrecht, The Netherlands., Lijnzaad P; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., Johnson HR; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.; Oncode Institute, Utrecht, The Netherlands., Korving J; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center (UMC) Utrecht, Utrecht, The Netherlands., Wehrens EJ; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.; Oncode Institute, Utrecht, The Netherlands., Holstege F; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., van Rheenen J; Oncode Institute, Utrecht, The Netherlands.; Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Drost J; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.; Oncode Institute, Utrecht, The Netherlands., Rios AC; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.; Oncode Institute, Utrecht, The Netherlands., Bos FL; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.; Oncode Institute, Utrecht, The Netherlands. |
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Jazyk: | angličtina |
Zdroj: | Developmental dynamics : an official publication of the American Association of Anatomists [Dev Dyn] 2021 Nov; Vol. 250 (11), pp. 1568-1583. Date of Electronic Publication: 2021 May 06. |
DOI: | 10.1002/dvdy.346 |
Abstrakt: | 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 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. (© 2021 The Authors. Developmental Dynamics published by Wiley Periodicals LLC on behalf of American Association of Anatomists.) |
Databáze: | MEDLINE |
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