Embryonic macrophages support endocrine commitment during human pancreatic differentiation.

Autor:	Migliorini A; McEwen Stem Cell Institute, University Health Network, Toronto, ON M5G 1L7, Canada. Electronic address: adriana.migliorini@uhn.ca., Ge S; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada., Atkins MH; McEwen Stem Cell Institute, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada., Oakie A; McEwen Stem Cell Institute, University Health Network, Toronto, ON M5G 1L7, Canada., Sambathkumar R; McEwen Stem Cell Institute, University Health Network, Toronto, ON M5G 1L7, Canada., Kent G; McEwen Stem Cell Institute, University Health Network, Toronto, ON M5G 1L7, Canada., Huang H; McEwen Stem Cell Institute, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada., Sing A; McEwen Stem Cell Institute, University Health Network, Toronto, ON M5G 1L7, Canada., Chua C; Toronto Centre for Liver Disease, Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 2C4, Canada; Institute of Medical Sciences, University of Toronto, Toronto, ON M5S 1A8, Canada., Gehring AJ; Toronto Centre for Liver Disease, Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 2C4, Canada; Institute of Medical Sciences, University of Toronto, Toronto, ON M5S 1A8, Canada., Keller GM; McEwen Stem Cell Institute, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada., Notta F; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada., Nostro MC; McEwen Stem Cell Institute, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Ajmera Transplant Centre, Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 2C4, Canada. Electronic address: cristina.nostro@uhn.ca.
Jazyk:	angličtina
Zdroj:	Cell stem cell [Cell Stem Cell] 2024 Oct 10. Date of Electronic Publication: 2024 Oct 10.
DOI:	10.1016/j.stem.2024.09.011
Abstrakt:	Organogenesis is a complex process that relies on a dynamic interplay between extrinsic factors originating from the microenvironment and tissue-specific intrinsic factors. For pancreatic endocrine cells, the local niche consists of acinar and ductal cells as well as neuronal, immune, endothelial, and stromal cells. Hematopoietic cells have been detected in human pancreas as early as 6 post-conception weeks, but whether they play a role during human endocrinogenesis remains unknown. To investigate this, we performed single-nucleus RNA sequencing (snRNA-seq) of the second-trimester human pancreas and identified a wide range of hematopoietic cells, including two distinct subsets of tissue-resident macrophages. Leveraging this discovery, we developed a co-culture system of human embryonic stem cell-derived endocrine-macrophage organoids to model their interaction in vitro. Here, we show that macrophages support the differentiation and viability of endocrine cells in vitro and enhance tissue engraftment, highlighting their potential role in tissue engineering strategies for diabetes. Competing Interests: Declaration of interests A.M., M.H.A., G.M.K., and M.C.N. are coinventors on one patent application related to this work. M.C.N. has a patent (WO2013163739A1) licensed to Sernova Inc. (Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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