Dynamic tracking of native precursors in adult mice
Hematopoietic dysfunction has been associated with a reduction in the number of active precursors. However, precursor quantification at homeostasis and under diseased conditions is constrained by the scarcity of available methods. To address this issue, we optimized a method for quantifying a wide r...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2024-12-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/97504 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850245656102305792 |
|---|---|
| author | Suying Liu Sarah E Adams Haotian Zheng Juliana Ehnot Seul K Jung Greer Jeffrey Theresa Menna Louise Purton Hongzhe Lee Peter Kurre |
| author_facet | Suying Liu Sarah E Adams Haotian Zheng Juliana Ehnot Seul K Jung Greer Jeffrey Theresa Menna Louise Purton Hongzhe Lee Peter Kurre |
| author_sort | Suying Liu |
| collection | DOAJ |
| description | Hematopoietic dysfunction has been associated with a reduction in the number of active precursors. However, precursor quantification at homeostasis and under diseased conditions is constrained by the scarcity of available methods. To address this issue, we optimized a method for quantifying a wide range of hematopoietic precursors. Assuming the random induction of a stable label in precursors following a binomial distribution, estimates depend on the inverse correlation between precursor numbers and the variance of precursor labeling among independent samples. Experimentally validated to cover the full dynamic range of hematopoietic precursors in mice (1–105), we utilized this approach to demonstrate that thousands of precursors, which emerge after modest expansion during fetal-to-adult transition, contribute to native and perturbed hematopoiesis. We further estimated the number of precursors in a mouse model of Fanconi Anemia, showcasing how repopulation deficits can be classified as autologous (cell proliferation) and non-autologous (lack of precursor). Our results support an accessible and reliable approach for precursor quantification, emphasizing the contemporary perspective that native hematopoiesis is highly polyclonal. |
| format | Article |
| id | doaj-art-2fec09e563a141b8b74c7ab47651be0e |
| institution | OA Journals |
| issn | 2050-084X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-2fec09e563a141b8b74c7ab47651be0e2025-08-20T01:59:22ZengeLife Sciences Publications LtdeLife2050-084X2024-12-011310.7554/eLife.97504Dynamic tracking of native precursors in adult miceSuying Liu0https://orcid.org/0000-0003-3947-8151Sarah E Adams1Haotian Zheng2Juliana Ehnot3Seul K Jung4Greer Jeffrey5Theresa Menna6Louise Purton7Hongzhe Lee8Peter Kurre9https://orcid.org/0000-0003-2747-0099Comprehensive Bone Marrow Failure Center, Children’s Hospital of Philadelphia, Philadelphia, United States; Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesComprehensive Bone Marrow Failure Center, Children’s Hospital of Philadelphia, Philadelphia, United States; Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesDepartment of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, United StatesComprehensive Bone Marrow Failure Center, Children’s Hospital of Philadelphia, Philadelphia, United States; Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesComprehensive Bone Marrow Failure Center, Children’s Hospital of Philadelphia, Philadelphia, United States; Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesComprehensive Bone Marrow Failure Center, Children’s Hospital of Philadelphia, Philadelphia, United States; Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesComprehensive Bone Marrow Failure Center, Children’s Hospital of Philadelphia, Philadelphia, United States; Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesStem Cell Regulation Unit, St. Vincent's Institute of Medical Research, Fitzroy, Australia; Department of Medicine, The University of Melbourne, Parkville, AustraliaDepartment of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, United StatesComprehensive Bone Marrow Failure Center, Children’s Hospital of Philadelphia, Philadelphia, United States; Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesHematopoietic dysfunction has been associated with a reduction in the number of active precursors. However, precursor quantification at homeostasis and under diseased conditions is constrained by the scarcity of available methods. To address this issue, we optimized a method for quantifying a wide range of hematopoietic precursors. Assuming the random induction of a stable label in precursors following a binomial distribution, estimates depend on the inverse correlation between precursor numbers and the variance of precursor labeling among independent samples. Experimentally validated to cover the full dynamic range of hematopoietic precursors in mice (1–105), we utilized this approach to demonstrate that thousands of precursors, which emerge after modest expansion during fetal-to-adult transition, contribute to native and perturbed hematopoiesis. We further estimated the number of precursors in a mouse model of Fanconi Anemia, showcasing how repopulation deficits can be classified as autologous (cell proliferation) and non-autologous (lack of precursor). Our results support an accessible and reliable approach for precursor quantification, emphasizing the contemporary perspective that native hematopoiesis is highly polyclonal.https://elifesciences.org/articles/97504hematopoiesisclonal diversityFanconi Anemia |
| spellingShingle | Suying Liu Sarah E Adams Haotian Zheng Juliana Ehnot Seul K Jung Greer Jeffrey Theresa Menna Louise Purton Hongzhe Lee Peter Kurre Dynamic tracking of native precursors in adult mice eLife hematopoiesis clonal diversity Fanconi Anemia |
| title | Dynamic tracking of native precursors in adult mice |
| title_full | Dynamic tracking of native precursors in adult mice |
| title_fullStr | Dynamic tracking of native precursors in adult mice |
| title_full_unstemmed | Dynamic tracking of native precursors in adult mice |
| title_short | Dynamic tracking of native precursors in adult mice |
| title_sort | dynamic tracking of native precursors in adult mice |
| topic | hematopoiesis clonal diversity Fanconi Anemia |
| url | https://elifesciences.org/articles/97504 |
| work_keys_str_mv | AT suyingliu dynamictrackingofnativeprecursorsinadultmice AT saraheadams dynamictrackingofnativeprecursorsinadultmice AT haotianzheng dynamictrackingofnativeprecursorsinadultmice AT julianaehnot dynamictrackingofnativeprecursorsinadultmice AT seulkjung dynamictrackingofnativeprecursorsinadultmice AT greerjeffrey dynamictrackingofnativeprecursorsinadultmice AT theresamenna dynamictrackingofnativeprecursorsinadultmice AT louisepurton dynamictrackingofnativeprecursorsinadultmice AT hongzhelee dynamictrackingofnativeprecursorsinadultmice AT peterkurre dynamictrackingofnativeprecursorsinadultmice |