PMID- 28455412 OWN - NLM STAT- MEDLINE DCOM- 20180509 LR - 20181113 IS - 1477-9137 (Electronic) IS - 0021-9533 (Print) IS - 0021-9533 (Linking) VI - 130 IP - 12 DP - 2017 Jun 15 TI - In vivo reprogramming of non-mammary cells to an epithelial cell fate is independent of amphiregulin signaling. PG - 2018-2025 LID - 10.1242/jcs.200030 [doi] AB - Amphiregulin (AREG)(-/-) mice demonstrate impaired mammary development and form only rudimentary ductal epithelial trees; however, AREG(-/-) glands are still capable of undergoing alveologenesis and lactogenesis during pregnancy. Transplantation of AREG(-/-) mammary epithelial cells into cleared mouse mammary fat pads results in a diminished capacity for epithelial growth ( approximately 15%) as compared to that of wild-type mammary epithelial cells. To determine whether estrogen receptor alpha (ERalpha, also known as ESR1) and/or AREG signaling were necessary for non-mammary cell redirection, we inoculated either ERalpha(-/-) or AREG(-/-) mammary cells with non-mammary progenitor cells (WAP-Cre/Rosa26LacZ+ male testicular cells or GFP-positive embryonic neuronal stem cells). ERalpha(-/-) cells possessed a limited ability to grow or reprogram non-mammary cells in transplanted mammary fat pads. AREG(-/-) mammary cells were capable of redirecting both types of non-mammary cell populations to mammary phenotypes in regenerating mammary outgrowths. Transplantation of fragments from AREG-reprogrammed chimeric outgrowths resulted in secondary outgrowths in six out of ten fat pads, demonstrating the self-renewing capacity of the redirected non-mammary cells to contribute new progeny to chimeric outgrowths. Nestin was detected at the leading edges of developing alveoli, suggesting that its expression may be essential for lobular expansion. CI - (c) 2017. Published by The Company of Biologists Ltd. FAU - George, Andrea L AU - George AL AD - Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. FAU - Boulanger, Corinne A AU - Boulanger CA AD - Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. FAU - Anderson, Lisa H AU - Anderson LH AUID- ORCID: 0000-0001-9541-1950 AD - Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. FAU - Cagnet, Stephanie AU - Cagnet S AD - Ecole Polytechnique Federale de Lausanne (EPFL), ISREC-Swiss Institute for Experimental Research, SV.832 Station 19, Lausanne CH-1015, Switzerland. FAU - Brisken, Cathrin AU - Brisken C AD - Ecole Polytechnique Federale de Lausanne (EPFL), ISREC-Swiss Institute for Experimental Research, SV.832 Station 19, Lausanne CH-1015, Switzerland. FAU - Smith, Gilbert H AU - Smith GH AUID- ORCID: 0000-0002-1908-5425 AD - Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA smithg@mail.nih.gov. LA - eng PT - Journal Article DEP - 20170428 PL - England TA - J Cell Sci JT - Journal of cell science JID - 0052457 RN - 0 (Amphiregulin) RN - 0 (Areg protein, mouse) RN - 0 (Estrogen Receptor alpha) RN - 0 (Estrogens) RN - 147336-22-9 (Green Fluorescent Proteins) SB - IM MH - Amphiregulin/*genetics MH - Animals MH - Cell Differentiation MH - *Cell Lineage MH - Cell Proliferation MH - Cell Transplantation MH - *Cellular Reprogramming MH - Cerebral Cortex/embryology MH - Embryonic Stem Cells/cytology MH - Epithelial Cells/*cytology MH - Estrogen Receptor alpha/genetics MH - Estrogens/metabolism MH - Female MH - Green Fluorescent Proteins/metabolism MH - Male MH - Mammary Glands, Animal/cytology MH - Mice MH - Mice, Nude MH - Mice, Transgenic MH - Neural Stem Cells/cytology MH - Pregnancy MH - *Signal Transduction MH - Spermatozoa/metabolism MH - Testis/metabolism PMC - PMC5482980 OTO - NOTNLM OT - Amphiregulin OT - Estrogen OT - Mammary OT - Reprogramming OT - Stem cells COIS- Competing interestsThe authors declare no competing or financial interests. EDAT- 2017/04/30 06:00 MHDA- 2018/05/10 06:00 PMCR- 2018/06/15 CRDT- 2017/04/30 06:00 PHST- 2016/11/28 00:00 [received] PHST- 2017/04/24 00:00 [accepted] PHST- 2017/04/30 06:00 [pubmed] PHST- 2018/05/10 06:00 [medline] PHST- 2017/04/30 06:00 [entrez] PHST- 2018/06/15 00:00 [pmc-release] AID - jcs.200030 [pii] AID - JCS200030 [pii] AID - 10.1242/jcs.200030 [doi] PST - ppublish SO - J Cell Sci. 2017 Jun 15;130(12):2018-2025. doi: 10.1242/jcs.200030. Epub 2017 Apr 28.