Postnatal conservation of human blood- and marrow-specific CD34+ hematopoietic phenotypes

Hammond, Colin A.; Eaves, Connie J.

doi:10.1016/j.exphem.2022.03.004

Cited by 1 publication

(1 citation statement)

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“…We first measured the percentage of CD34 + CD49f + early HSC in the BM of CN (N=3), CyN (N=8) and healthy donors’ (HD) cord blood (CB) cells (N=6) by flow cytometry. Since the percentages of CD49f + cells from CB CD34 + cells are comparable to the percentages of CD34 + CD49f + cells from the BM of children and young adults 39 we used them for comparison. We observed a median of 2.8% (range, 1.2-4.6%) and 2.8% (range, 1.7-7.3%) CD34 + CD49f + eHSC in CN and CyN patients` BM, respectively.…”

Section: Resultsmentioning

confidence: 99%

Differential transcriptional control of hematopoiesis in congenital and cycling neutropenia patients harboring <i>ELANE</i> mutations

Zeidler,

Borbaran-Bravo,

Dannenmann

et al. 2023

haematol

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Mutations in the ELANE gene, encoding the neutrophil elastase (NE) protein, are responsible for most CyN cases and approximately 25 % of CN cases. In CN and in CyN, a median of 2.8 % of CD34+ cells were early CD49f+ hematopoietic stem cells (eHSC) that did not express ELANE and thus escape from the unfolded protein response (UPR) caused by mutated NE. In CyN, the CD49f+ cells respond to G-CSF with a significant upregulation of the hematopoietic stem-cell-specific transcription factors, C/EBP/, MLL1, HOXA9, MEIS1, and HLF during the ascending arm of the cycle, resulting in the differentiation of myeloid cells to mature neutrophils at the cycle peak. However, NE protein released by neutrophils at the cycle's peak caused a negative feedback loop on granulopoiesis through the proteolytic digestion of G-CSF. In contrast, in CN patients, CD49f+ cells failed to express mRNA levels of HSC-specific transcription factors mentioned above. Rescue of C/EBP//expression in CN restored granulopoiesis.

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Section: Resultsmentioning

confidence: 99%