LGR6 marks nephron progenitor cells

Ravian L van Ineveld, Thanasis Margaritis, Berend A P Kooiman, Femke Groenveld, Hendrikus C R Ariese, Philip Lijnzaad, Hannah R Johnson, Jeroen Korving, Ellen J Wehrens, Frank Holstege, Jacco van Rheenen, Jarno Drost, Anne C Rios, Frank L Bos

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review


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.

Originele taal-2Engels
Pagina's (van-tot)1568-1583
Aantal pagina's16
TijdschriftDevelopmental dynamics : an official publication of the American Association of Anatomists
Nummer van het tijdschrift11
StatusGepubliceerd - nov. 2021


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