Pre-existing beta cells but not progenitors contribute to new beta cells in the adult pancreas

Zhao, Huan; Huang, Xiuzhen; Liu, Zixin; Pu, Wenjuan; Lv, Zan; He, Lingjuan; Li, Yan; Zhou, Qiao; Lui, Kathy O.; Zhou, Bin

doi:10.1038/s42255-021-00364-0

Cited by 49 publications

(35 citation statements)

References 52 publications

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“…In contrast, use of promoters such as Krt19, Mucin1, Sox9, Hes1 and Hnf1b has not shown ductal contribution to β cell regeneration ( Kopinke et al., 2011 ; Kopinke and Murtaugh, 2010 ; Means et al., 2008 ; Solar et al., 2009 ). Likewise, dilution of labeled β cells over time in homeostasis and after PDL has been reported ( Van de Casteele et al., 2013 ), but has not been seen in other studies ( Dor et al., 2004 ; Zhao et al., 2021 ). Thus, the question of whether ductal cells can differentiate into endocrine cells is controversial and unresolved.…”

Section: Introductionmentioning

confidence: 81%

Ductal Ngn3-expressing progenitors contribute to adult β cell neogenesis in the pancreas

et al. 2021

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Summary Ductal cells have been proposed as a source of adult β cell neogenesis, but this has remained controversial. By combining lineage tracing, 3D imaging, and single-cell RNA sequencing (scRNA-seq) approaches, we show that ductal cells contribute to the β cell population over time. Lineage tracing using the Neurogenin3 (Ngn3)-CreERT line identified ductal cells expressing the endocrine master transcription factor Ngn3 that were positive for the δ cell marker somatostatin and occasionally co-expressed insulin. The number of hormone-expressing ductal cells was increased in Akita +/− diabetic mice, and ngn3 heterozygosity accelerated diabetes onset. scRNA-seq of Ngn3 lineage-traced islet cells indicated that duct-derived somatostatin-expressing cells, some of which retained expression of ductal markers, gave rise to β cells. This study identified Ngn3-expressing ductal cells as a source of adult β cell neogenesis in homeostasis and diabetes, suggesting that this mechanism, in addition to β cell proliferation, maintains the adult islet β cell population.

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Section: Introductionmentioning

confidence: 81%

Ductal Ngn3-expressing progenitors contribute to adult β cell neogenesis in the pancreas

et al. 2021

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“…It is noteworthy that tamoxifen-independent recombination in RIP-CreER, a technical glitch, has been reported (Liu et al, 2010). Thus, the results generated from RIP-CreER or, similarly, INS2-Dre and INS2-DreER (Zhao et al, 2021) tracing do not exclude the possible existence and contribution of stem/progenitor cells, and there lies a possibility that these CreER/DreER models may have accidentally labeled stem/progenitor cells.…”

Section: Debate On the Existence Of Adult Pancreatic Islet Stem Cellsmentioning

confidence: 98%

“…Moreover, hepatocytes are heterogeneous from periportal to pericentral through scRNAseq (Aizarani et al, 2019). Recently, the complex lineage tracing strategy confirmed that the midlobular zone 2 is the major contributor to hepatocyte proliferation during homeostasis and identified other hepatocyte subsets that contribute to regeneration after liver injury (He et al, 2021;Wei et al, 2021) (Figure 3).…”

Section: Mature Hepatocyte In Liver Homeostasismentioning

confidence: 98%

Recent advances in tissue stem cells

et al. 2021

Sci. China Life Sci.

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Stem cells are undifferentiated cells capable of self-renewal and differentiation, giving rise to specialized functional cells. Stem cells are of pivotal importance for organ and tissue development, homeostasis, and injury and disease repair. Tissue-specific stem cells are a rare population residing in specific tissues and present powerful potential for regeneration when required. They are usually named based on the resident tissue, such as hematopoietic stem cells and germline stem cells. This review discusses the recent advances in stem cells of various tissues, including neural stem cells, muscle stem cells, liver progenitors, pancreatic islet stem/progenitor cells, intestinal stem cells, and prostate stem cells, and the future perspectives for tissue stem cell research. neural stem cells, muscle stem cells, liver progenitors, pancreatic islet stem/progenitor cells, intestinal stem cells, prostate stem cells

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“…A dual-recombinase-mediated genetic tracing system was developed to improve the accuracy of the Cre-loxP system (He et al, 2017(He et al, , 2018. Recently, the origin of new beta-cells in the adult pancreas and the distinct proliferation capability of hepatocytes in different zones of the liver were successfully revealed by applying this system (He et al, 2021;Zhao et al, 2021).…”

Section: Technical Advancesmentioning

confidence: 99%

The rise of developmental biology in China

et al. 2021

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The developmental biology community is growing rapidly in China.Here, we will discuss the past, present and future of developmental biology in China to gain an overview. Brief information about the related societies and current government funding support will be given. Research spotlights and several technical advances during the last decade or so will be presented. Lastly, the current trends in developmental biology studies in China will be discussed.

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Pre-existing beta cells but not progenitors contribute to new beta cells in the adult pancreas

Cited by 49 publications

References 52 publications

Ductal Ngn3-expressing progenitors contribute to adult β cell neogenesis in the pancreas

Ductal Ngn3-expressing progenitors contribute to adult β cell neogenesis in the pancreas

Recent advances in tissue stem cells

The rise of developmental biology in China

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