Tissue homeostasis, accomplished through the self-renewai and differentiation of resident stem cells, is critical for the maintenance of adult tissues throughout an animal's lifetime, Adult Drosophila Malpighian tubu...Tissue homeostasis, accomplished through the self-renewai and differentiation of resident stem cells, is critical for the maintenance of adult tissues throughout an animal's lifetime, Adult Drosophila Malpighian tubules (MTs or fly kidney) are maintained by renal and nephric stem cells (RNSCs) via self-renewing divisions, however, it is unclear how RNSC proliferation and differentiation are regulated. Here we show that EGFR/MAPK signaling is dispensable for RNSC maintenance, but required for RNSC proliferation in vivo. Inacti- vation of the EGFR/MAPK pathway blocks or greatly retards RNSC cell cycle progression; conversely, over-activation of EGFR/MAPK signaling results in RNSC over-proliferation and disrupts the normal differentiation of renablasts (RBs), the immediate daughters of RNSC divisions. Our data further suggest that EGFR/MAPK signaling functions independently of JAK/STAT signaling and that dMyc and CycE partially mediate EGFR/MAPK signaling in MTs. Together, our data suggest a principal role of EGFR/MAPK signaling in regulating RNSC proliferation, which may provide important clues for understanding mammalian kidney repair and regeneration following injury.展开更多
Acute kidney injury is a serious global health problem and determinant of morbidity and mortality. Recent advancements in the fi eld of stem cell research raise hopes for stem cell-based regenerative approaches to tre...Acute kidney injury is a serious global health problem and determinant of morbidity and mortality. Recent advancements in the fi eld of stem cell research raise hopes for stem cell-based regenerative approaches to treat acute kidney diseases. In this review, the authors summarized the latest research advances of the adult resident renal progenitor cells(ARPCs) on kidney repair, the role of ARPCs on tubular regeneration after acute kidney injury, the current understanding of the mechanisms rela ted to ARPC activation and modulation, as well as the challenges that remain to be faced.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.31271582)Temasek Life Sciences Laboratory and Singapore Millennium FoundationBeijing Municipal Commission of Education(No.010135336400)
文摘Tissue homeostasis, accomplished through the self-renewai and differentiation of resident stem cells, is critical for the maintenance of adult tissues throughout an animal's lifetime, Adult Drosophila Malpighian tubules (MTs or fly kidney) are maintained by renal and nephric stem cells (RNSCs) via self-renewing divisions, however, it is unclear how RNSC proliferation and differentiation are regulated. Here we show that EGFR/MAPK signaling is dispensable for RNSC maintenance, but required for RNSC proliferation in vivo. Inacti- vation of the EGFR/MAPK pathway blocks or greatly retards RNSC cell cycle progression; conversely, over-activation of EGFR/MAPK signaling results in RNSC over-proliferation and disrupts the normal differentiation of renablasts (RBs), the immediate daughters of RNSC divisions. Our data further suggest that EGFR/MAPK signaling functions independently of JAK/STAT signaling and that dMyc and CycE partially mediate EGFR/MAPK signaling in MTs. Together, our data suggest a principal role of EGFR/MAPK signaling in regulating RNSC proliferation, which may provide important clues for understanding mammalian kidney repair and regeneration following injury.
基金supported by the Medicine Project of Nanjing Military Command (No. 2008132002)the Specific Project of Nanjing Military Command (No. ZX07)the National Natural Science Foundation of China (No. 81300568)
文摘Acute kidney injury is a serious global health problem and determinant of morbidity and mortality. Recent advancements in the fi eld of stem cell research raise hopes for stem cell-based regenerative approaches to treat acute kidney diseases. In this review, the authors summarized the latest research advances of the adult resident renal progenitor cells(ARPCs) on kidney repair, the role of ARPCs on tubular regeneration after acute kidney injury, the current understanding of the mechanisms rela ted to ARPC activation and modulation, as well as the challenges that remain to be faced.