Publication: Mouse models of neutropenia reveal progenitor-stage-specific defects
Issued Date
2020-01-01
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ISSN
14764687
00280836
00280836
Other identifier(s)
2-s2.0-85084063089
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Mahidol University
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SCOPUS
Bibliographic Citation
Nature. (2020)
Suggested Citation
David E. Muench, Andre Olsson, Kyle Ferchen, Giang Pham, Rachel A. Serafin, Somchai Chutipongtanate, Pankaj Dwivedi, Baobao Song, Stuart Hay, Kashish Chetal, Lisa R. Trump-Durbin, Jayati Mookerjee-Basu, Kejian Zhang, Jennifer C. Yu, Carolyn Lutzko, Kasiani C. Myers, Kristopher L. Nazor, Kenneth D. Greis, Dietmar J. Kappes, Sing Sing Way, Nathan Salomonis, H. Leighton Grimes Mouse models of neutropenia reveal progenitor-stage-specific defects. Nature. (2020). doi:10.1038/s41586-020-2227-7 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/56367
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Title
Mouse models of neutropenia reveal progenitor-stage-specific defects
Author(s)
David E. Muench
Andre Olsson
Kyle Ferchen
Giang Pham
Rachel A. Serafin
Somchai Chutipongtanate
Pankaj Dwivedi
Baobao Song
Stuart Hay
Kashish Chetal
Lisa R. Trump-Durbin
Jayati Mookerjee-Basu
Kejian Zhang
Jennifer C. Yu
Carolyn Lutzko
Kasiani C. Myers
Kristopher L. Nazor
Kenneth D. Greis
Dietmar J. Kappes
Sing Sing Way
Nathan Salomonis
H. Leighton Grimes
Andre Olsson
Kyle Ferchen
Giang Pham
Rachel A. Serafin
Somchai Chutipongtanate
Pankaj Dwivedi
Baobao Song
Stuart Hay
Kashish Chetal
Lisa R. Trump-Durbin
Jayati Mookerjee-Basu
Kejian Zhang
Jennifer C. Yu
Carolyn Lutzko
Kasiani C. Myers
Kristopher L. Nazor
Kenneth D. Greis
Dietmar J. Kappes
Sing Sing Way
Nathan Salomonis
H. Leighton Grimes
Abstract
© 2020, The Author(s), under exclusive licence to Springer Nature Limited. Advances in genetics and sequencing have identified a plethora of disease-associated and disease-causing genetic alterations. To determine causality between genetics and disease, accurate models for molecular dissection are required; however, the rapid expansion of transcriptional populations identified through single-cell analyses presents a major challenge for accurate comparisons between mutant and wild-type cells. Here we generate mouse models of human severe congenital neutropenia (SCN) using patient-derived mutations in the GFI1 transcription factor. To determine the effects of SCN mutations, we generated single-cell references for granulopoietic genomic states with linked epitopes1, aligned mutant cells to their wild-type equivalents and identified differentially expressed genes and epigenetic loci. We find that GFI1-target genes are altered sequentially, as cells go through successive states of differentiation. These insights facilitated the genetic rescue of granulocytic specification but not post-commitment defects in innate immune effector function, and underscore the importance of evaluating the effects of mutations and therapy within each relevant cell state.