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| Status |
Public on May 14, 2022 |
| Title |
Developmental cues license emergency megakaryopoiesis in hematopoietic stem cells [bulk RNA-seq & ATAC-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The fetal to adult switch in mouse hematopoietic stem cell (HSC) behavior is characterized by entry into quiescence and alterations in lineage output. Here we identify the ability of HSCs to undergo emergency megakaryopoiesis following acute inflammatory insult as an outcome of this developmental switch. Single cell accessibility mapping of fetal and adult HSCs resolves a heterogeneous chromatin landscape consistent with a two-step megakaryocyte lineage priming process. Importantly, we demonstrate that the accumulation of megakaryocyte primed HSCs is under the control of the developmentally restricted Lin28b RNA binding protein. Persistent Lin28b protein expression in postnatal HSCs delays the formation of a primed HSC pool and limits emergency megakaryopoiesis. Taken together, we identify Lin28b as a negative regulator of a megakaryocyte primed HSC state that is enforced at the chromatin level during unperturbed organismal development. These findings highlight the ontogenically timed onset of inflammatory responsiveness, with important implications for the delicate balance between host protection and tissue damage during neonatal life.
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| Overall design |
Bulk RNA- and ATAC-seq was used to compare E14.5 fetal liver and adult bone marrow hematopoietic stem cells(HSC) and lymphoid primed multipotent progenitors (LMPP). Biological replicates (n) as follows: RNA-seq ABM HSC (n=3), RNA-seq FL HSC (n=2), RNA-seq ABM LMPP (n=3), RNA-seq FL LMPP (n=3), ATAC-seq ABM HSC (n=2), ATAC-seq FL HSC (n=2), ATAC-seq ABM LMPP (n=2), ATAC-seq FL LMPP (n=2).
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| Contributor(s) |
Kristiansen TA, Ungerbäck J, Yuan J |
| Citation(s) |
35584393 |
| |
| Submission date |
Nov 18, 2020 |
| Last update date |
Aug 14, 2022 |
| Contact name |
Jonas Ungerback |
| E-mail(s) |
jonas.ungerback@med.lu.se
|
| Phone |
+46733106131
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| Organization name |
Lund University
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| Department |
Division of Molecular Hematology
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| Lab |
Mikael Sigvardsson
|
| Street address |
Klinikgatan 26
|
| City |
Lund |
| ZIP/Postal code |
22362 |
| Country |
Sweden |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (19)
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| This SubSeries is part of SuperSeries: |
| GSE161725 |
Developmental cues license emergency megakaryopoiesis in hematopoietic stem cells |
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| Relations |
| BioProject |
PRJNA679257 |
| SRA |
SRP293095 |
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