Dataset Information

Neurogenin 3+ cells contribute to ?-cell neogenesis and proliferation in injured adult mouse pancreas.

ABSTRACT: We previously showed that injury by partial duct ligation (PDL) in adult mouse pancreas activates Neurogenin 3 (Ngn3)(+) progenitor cells that can differentiate to ? cells ex vivo. Here we evaluate the role of Ngn3(+) cells in ? cell expansion in situ. PDL not only induced doubling of the ? cell volume but also increased the total number of islets. ? cells proliferated without extended delay (the so-called 'refractory' period), their proliferation potential was highest in small islets, and 86% of the ? cell expansion was attributable to proliferation of pre-existing ? cells. At sufficiently high Ngn3 expression level, upto 14% of all ? cells and 40% of small islet ? cells derived from non-? cells. Moreover, ? cell proliferation was blunted by a selective ablation of Ngn3(+) cells but not by conditional knockout of Ngn3 in pre-existing ? cells supporting a key role for Ngn3(+) insulin(-) cells in ? cell proliferation and expansion. We conclude that Ngn3(+) cell-dependent proliferation of pre-existing and newly-formed ? cells as well as reprogramming of non-? cells contribute to in vivo ? cell expansion in the injured pancreas of adult mice.

SUBMITTER: Van de Casteele M

PROVIDER: S-EPMC3613830 | biostudies-other | 2013

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Neurogenin 3+ cells contribute to β-cell neogenesis and proliferation in injured adult mouse pancreas.

Van de Casteele M M Leuckx G G Baeyens L L Cai Y Y Yuchi Y Y Coppens V V De Groef S S Eriksson M M Svensson C C Ahlgren U U Ahnfelt-Rønne J J Madsen O D OD Waisman A A Dor Y Y Jensen J N JN Heimberg H H

Cell death & disease 20130307

We previously showed that injury by partial duct ligation (PDL) in adult mouse pancreas activates Neurogenin 3 (Ngn3)(+) progenitor cells that can differentiate to β cells ex vivo. Here we evaluate the role of Ngn3(+) cells in β cell expansion in situ. PDL not only induced doubling of the β cell volume but also increased the total number of islets. β cells proliferated without extended delay (the so-called 'refractory' period), their proliferation potential was highest in small islets, and 86% o ...[more]

PMID: 23470530

Similar Datasets

Project description:Studies have identified multi-potent stem cells in the adult mammary gland. More recent studies have suggested that the embryonic mammary gland may also contain stem/progenitor cells that contribute to initial ductal development. We were interested in determining whether embryonic cells might also directly contribute to long-lived stem cells that support homeostasis and development in the adult mammary gland.We used DNA-label retention to detect long label-retaining cells in the mammary gland. Mouse embryos were labeled with 5-ethynl-2'-deoxyuridine (EdU) between embryonic day 14.5 and embryonic day 18.5 and were subsequently sacrificed and examined for EdU retention at various intervals after birth. EdU retaining cells were co-stained for various lineage markers and identified after fluorescence activated cell sorting analysis of specific epithelial subsets. EdU-labeled mice were subjected to subsequent 5-bromo-2'-deoxyuridine administration to determine whether EdU-labeled cells could re-enter the cell cycle. Finally, EdU-labeled cells were grown under non-adherent conditions to assess their ability to form mammospheres.We demonstrate embryonically-derived, long label-retaining cells (eLLRCs) in the adult mammary gland. eLLRCs stain for basal markers and are enriched within the mammary stem cell population identified by cell sorting. eLLRCs are restricted to the primary ducts near the nipple region. Interestingly, long label retaining cells (labeled during puberty) are found just in front of the eLLRCs, near where the ends of the ducts had been at the time of DNA labeling in early puberty. A subset of eLLRCs becomes mitotically active during periods of mammary growth and in response to ovarian hormones. Finally, we show that eLLRCs are contained within primary and secondary mammospheres.Our findings suggest that a subset of proliferating embryonic cells subsequently becomes quiescent and contributes to the pool of long-lived mammary stem cells in the adult. eLLRCs can re-enter the cell cycle, produce both mammary lineages and self-renew. Thus, our studies have identified a putative stem/progenitor cell population of embryonic origin. Further study of these cells will contribute to an understanding of how quiescent stem cells are generated during development and how fetal exposures may alter future breast cancer risk in adults.

Dataset Information

Neurogenin 3+ cells contribute to ?-cell neogenesis and proliferation in injured adult mouse pancreas.

Publications

Neurogenin 3+ cells contribute to β-cell neogenesis and proliferation in injured adult mouse pancreas.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets