{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:43:36Z","timestamp":1760147016614,"version":"build-2065373602"},"reference-count":31,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FAVOR NIH T32 Training","award":["5T32AI125222-05","NIH P30 DK026743","NIH P30 DK063720","P30 DK026743"],"award-info":[{"award-number":["5T32AI125222-05","NIH P30 DK026743","NIH P30 DK063720","P30 DK026743"]}]},{"name":"American Pediatric Surgical Association Foundation Jay Grosfeld, MD Scholar Award (AN)","award":["5T32AI125222-05","NIH P30 DK026743","NIH P30 DK063720","P30 DK026743"],"award-info":[{"award-number":["5T32AI125222-05","NIH P30 DK026743","NIH P30 DK063720","P30 DK026743"]}]},{"name":"American College of Surgeons Faculty Research Fellowship (AN)","award":["5T32AI125222-05","NIH P30 DK026743","NIH P30 DK063720","P30 DK026743"],"award-info":[{"award-number":["5T32AI125222-05","NIH P30 DK026743","NIH P30 DK063720","P30 DK026743"]}]},{"name":"UCSF Liver Center Pilot Award","award":["5T32AI125222-05","NIH P30 DK026743","NIH P30 DK063720","P30 DK026743"],"award-info":[{"award-number":["5T32AI125222-05","NIH P30 DK026743","NIH P30 DK063720","P30 DK026743"]}]},{"name":"UCSF Parnassus Flow Cytometry Core","award":["5T32AI125222-05","NIH P30 DK026743","NIH P30 DK063720","P30 DK026743"],"award-info":[{"award-number":["5T32AI125222-05","NIH P30 DK026743","NIH P30 DK063720","P30 DK026743"]}]},{"DOI":"10.13039\/100000062","name":"core resources of the UCSF Liver Cente","doi-asserted-by":"publisher","award":["5T32AI125222-05","NIH P30 DK026743","NIH P30 DK063720","P30 DK026743"],"award-info":[{"award-number":["5T32AI125222-05","NIH P30 DK026743","NIH P30 DK063720","P30 DK026743"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Biliary atresia (BA) is a progressive pediatric inflammatory disease of the liver that leads to cirrhosis and necessitates liver transplantation. The rapid progression from liver injury to liver failure in children with BA suggests that factors specific to the perinatal hepatic environment are important for disease propagation. Hematopoietic stem and progenitor cells (HSPCs) reside in the fetal liver and are known to serve as central hubs of inflammation. We hypothesized that HSPCs are critical for the propagation of perinatal liver injury (PLI). Methods: Newborn BALB\/c mice were injected with rhesus rotavirus (RRV) to induce PLI or with PBS as control. Livers were compared using histology and flow cytometry. To determine the effects of HSPCs on PLI, RRV-infected neonatal mice were administered anti-CD47 and anti-CD117 to deplete HSPCs. Results: PLI significantly increased the number of common myeloid progenitors and the number of CD34+ hematopoietic progenitors. Elimination of HSPCs through antibody-mediated myeloablation rescued animals from PLI and significantly increased survival (RRV+isotype control 36.4% vs. RRV+myeloablation 77.8%, Chi-test = 0.003). Conclusions: HSPCs expand as a result of RRV infection and propagate PLI. Targeting of HSPCs may be useful in preventing and treating neonatal inflammatory diseases of the liver such as BA.<\/jats:p>","DOI":"10.3390\/jcm12010337","type":"journal-article","created":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T03:00:59Z","timestamp":1672628459000},"page":"337","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Neonatal Hepatic Myeloid Progenitors Expand and Propagate Liver Injury in Mice"],"prefix":"10.3390","volume":"12","author":[{"given":"Anas","family":"Alkhani","sequence":"first","affiliation":[{"name":"Department of Surgery, University of California, San Francisco, CA 94143, USA"},{"name":"The Liver Center, University of California, San Francisco, CA 94143, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cathrine","family":"Korsholm","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California, San Francisco, CA 94143, USA"},{"name":"The Liver Center, University of California, San Francisco, CA 94143, USA"},{"name":"Department of Comparative Pediatrics and Nutrition, University of Copenhagen, 1870 Frederiksberg C, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9265-6645","authenticated-orcid":false,"given":"Claire S.","family":"Levy","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California, San Francisco, CA 94143, USA"},{"name":"The Liver Center, University of California, San Francisco, CA 94143, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Mohamedaly","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California, San Francisco, CA 94143, USA"},{"name":"The Liver Center, University of California, San Francisco, CA 94143, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline C.","family":"Duwaerts","sequence":"additional","affiliation":[{"name":"The Liver Center, University of California, San Francisco, CA 94143, USA"},{"name":"Department of Medicine, University of California, San Francisco, CA 94143, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7339-8828","authenticated-orcid":false,"given":"Eric M.","family":"Pietras","sequence":"additional","affiliation":[{"name":"Division of Hematology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2200-6887","authenticated-orcid":false,"given":"Amar","family":"Nijagal","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California, San Francisco, CA 94143, USA"},{"name":"The Liver Center, University of California, San Francisco, CA 94143, USA"},{"name":"The Pediatric Liver Center, UCSF Benioff Childrens\u2019 Hospital, San Francisco, CA 94143, USA"},{"name":"Eli and Edythe Broad Center of Regeneration Medicine, University of California, San Francisco, CA 94143, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e13339","DOI":"10.1111\/petr.13339","article-title":"Acute-on-chronic liver failure in children with biliary atresia awaiting liver transplantation","volume":"23","author":"Grammatikopoulos","year":"2019","journal-title":"Pediatr. Transplant."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S23","DOI":"10.1097\/01.mpg.0000228197.28056.2f","article-title":"The Next Challenge in Pediatric Cholestasis: Deciphering the Pathogenesis of Biliary Atresia","volume":"43","author":"Bezerra","year":"2006","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"218","DOI":"10.12688\/f1000research.16732.1","article-title":"Recent advances in understanding biliary atresia","volume":"8","author":"Wehrman","year":"2019","journal-title":"F1000Research"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"7165","DOI":"10.1038\/s41598-020-64158-2","article-title":"Ly6c(Lo) non-classical monocytes promote resolution of rhesus rotavirus-mediated perinatal hepatic inflammation","volume":"10","author":"Alkhani","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.exphem.2013.01.009","article-title":"The migration of hematopoietic progenitors from the fetal liver to the fetal bone marrow: Lessons learned and possible clinical applications","volume":"41","author":"Ciriza","year":"2013","journal-title":"Exp. Hematol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1007\/s11427-018-9313-4","article-title":"Fetal liver: An ideal niche for hematopoietic stem cell expansion","volume":"61","author":"Gao","year":"2018","journal-title":"Sci. China Life Sci."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Otsuka, K.S., Nielson, C., Firpo, M.A., Park, A.H., and Beaudin, A.E. (2021). Early life inflammation and the developing hematopoietic and immune systems: The cochlea as a sensitive indicator of disruption. Cells, 10.","DOI":"10.3390\/cells10123596"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1016\/j.cell.2022.03.043","article-title":"Maladaptive innate immune training of myelopoiesis links inflammatory comorbidities","volume":"185","author":"Li","year":"2022","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1038\/s41590-019-0402-5","article-title":"Hematopoietic progenitor cells as integrative hubs for adaptation to and fine-tuning of inflammation","volume":"20","author":"Chavakis","year":"2019","journal-title":"Nat. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"179","DOI":"10.3389\/fimmu.2015.00179","article-title":"The complex myeloid network of the liver with diverse functional capacity at steady state and in inflammation","volume":"6","author":"Eckert","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"893","DOI":"10.3389\/fimmu.2019.00893","article-title":"The role of myeloid-derived cells in the progression of liver disease","volume":"10","author":"Weston","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1146\/annurev-immunol-051116-052415","article-title":"Immune Responses in the Liver","volume":"44","author":"Kubes","year":"2018","journal-title":"Annu. Rev. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"16878","DOI":"10.1038\/s41598-017-17204-5","article-title":"QuPath: Open source software for digital pathology image analysis","volume":"7","author":"Bankhead","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1002\/stem.1661","article-title":"Concise review: Evidence for CD34 as a common marker for diverse progenitors","volume":"32","author":"Sidney","year":"2014","journal-title":"Stem Cells"},{"key":"ref_15","first-page":"e58061","article-title":"Identification and isolation of oligopotent and lineage-committed myeloid progenitors from mouse bone marrow","volume":"2018","author":"Goodridge","year":"2018","journal-title":"J. Vis. Exp."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e55","DOI":"10.1038\/emm.2013.98","article-title":"Developmental changes in hematopoietic stem cell properties","volume":"45","author":"Copley","year":"2013","journal-title":"Exp. Mol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.jpedsurg.2013.09.064","article-title":"Rotavirus particles in the extrahepatic bile duct in experimental biliary atresia","volume":"49","author":"Pintelon","year":"2014","journal-title":"J. Pediatr. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"351ra105","DOI":"10.1126\/scitranslmed.aae0501","article-title":"Hematopoietic stem cell transplantation in immunocompetent hosts without radiation or chemotherapy","volume":"8","author":"Chhabra","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.1182\/blood-2018-06-858159","article-title":"Anti-CD117 antibody depletes normal and myelodysplastic syndrome human hematopoietic stem cells in xenografted mice","volume":"133","author":"Pang","year":"2019","journal-title":"Blood"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1002\/hep.25820","article-title":"Hematopoietic chimerism in liver transplantation patients and hematopoietic stem\/progenitor cells in adult human liver","volume":"56","author":"Wang","year":"2012","journal-title":"Hepatology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"612","DOI":"10.3389\/fcell.2020.00612","article-title":"Crosstalk Between the Hepatic and Hematopoietic Systems During Embryonic Development","volume":"8","author":"Peixoto","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/nri3062","article-title":"Inflammatory modulation of HSCs: Viewing the HSC as a foundation for the immune response","volume":"11","author":"King","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"123","DOI":"10.3389\/fimmu.2020.00123","article-title":"Training the Fetal Immune System Through Maternal Inflammation-A Layered Hygiene Hypothesis","volume":"11","author":"Apostol","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1016\/j.jpedsurg.2021.03.038","article-title":"Granulocyte-colony stimulating factor GCSF mobilizes hematopoietic stem cells in Kasai patients with biliary atresia in a phase 1 study and improves short term outcome","volume":"56","author":"Holterman","year":"2021","journal-title":"J. Pediatr. Surg."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"642546","DOI":"10.3389\/fimmu.2021.642546","article-title":"Bile Acids Impair Vaccine Response in Children With Biliary Atresia","volume":"12","author":"Liu","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2812","DOI":"10.1016\/j.vaccine.2009.02.094","article-title":"Humoral immunogenicity to measles, rubella, and varicella-zoster vaccines in biliary atresia children","volume":"27","author":"Wu","year":"2009","journal-title":"Vaccine"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1111\/petr.12194","article-title":"Rejection is less common in children undergoing liver transplantation for hepatoblastoma","volume":"18","author":"Ruth","year":"2014","journal-title":"Pediatr. Transplant."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/s41590-020-00845-6","article-title":"Trained immunity, tolerance, priming and differentiation: Distinct immunological processes","volume":"22","author":"Divangahi","year":"2021","journal-title":"Nat. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/s41577-020-0285-6","article-title":"Defining trained immunity and its role in health and disease","volume":"20","author":"Netea","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1182\/blood-2014-02-550327","article-title":"In utero depletion of fetal hematopoietic stem cells improves engraftment after neonatal transplantation in mice","volume":"124","author":"Derderian","year":"2014","journal-title":"Blood"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Liu, J., Wang, L., Zhao, F., Tseng, S., Narayanan, C., Shura, L., Willingham, S., Howard, M., Prohaska, S., and Volkmer, J. (2015). Pre-Clinical Development of a Humanized Anti-CD47 Antibody with Anti-Cancer Therapeutic Potential. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0137345"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/1\/337\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T17:55:34Z","timestamp":1760118934000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/1\/337"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,1]]},"references-count":31,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["jcm12010337"],"URL":"https:\/\/doi.org\/10.3390\/jcm12010337","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2023,1,1]]}}}